ARCHIVED - Chronic Diseases in Canada

 

Volume 29 · Supplement 1 · 2010

Ultraviolet radiation

Richard P. Gallagher, Tim K. Lee, Chris D. Bajdik and Marilyn Borugian

The major source of ultraviolet radiation is solar radiation or sunlight. However, exposure to artificial sources particularly through tanning salons is becoming more important in terms of human health effects, as use of these facilities by young people, has increased. The International Agency for Research on Cancer has noted that there is sufficient evidence from studies in animals and in man to establish ultraviolet radiation as a human carcinogen.

Skin cancer has been the most commonly studied cancer site with respect to UV radiation. The nature and timing of sun exposure appear to be important determinants of both the degree of risk and the type of skin cancer. Cutaneous malignant melanoma and basal cell cancer are much more strongly related to measures of intermittent ultraviolet exposure (particularly those of childhood or adolescence) than to measures of cumulative exposure. In contrast, squamous cell cancer is more strongly related to constant or cumulative sun exposure. Lip cancer is causally related to lifetime sun exposure.

It has been estimated that solar ultraviolet radiation accounts for approximately 93 percent of skin cancers and about half of lip cancers. This translates to approximately 4,500 life-threatening cancers (cutaneous malignant melanoma) per year in Canada, as well as 65,000 less serious cancers (basal cell cancer, squamous cell cancer and lip cancer). Appropriate clothing use, care not to sunburn and judicious use of sunscreens could prevent at least half of these and save approximately 450 lives per year. In addition, physician and public education programs can significantly increase the proportion of melanomas diagnosed early. Lesions that have not yet penetrated deeply are associated with a mortality rate of less than five percent.

Several recent studies suggest a possible inverse relationship between ultraviolet radiation exposure and risk of non-Hodgkin lymphoma, colon, breast and prostate cancer, and investigators have speculated that this might be due to the higher serum levels of vitamin D stimulated by high lifetime sun exposure. Further, studies conducted within cohorts using stored pre-diagnostic serum suggest that those with high levels of vitamin D have lower incidence rates of a number of malignancies, particularly colon cancer. However, since serum vitamin D levels can be raised through the use of supplements without increasing risk for skin lip and other known UV-related cancers, changes to health policy with regard to exposure are not merited at this point. Further research is needed in this area.

Introduction

Optical radiation within the electromagnetic spectrum includes ultraviolet radiation (UVR), visible light and infrared radiation. UVR, as used in this review, is defined as that radiation between 100 and 400 nanometres (nm) in length (WHO 1994).1 It is characterized further according to wave length into ultraviolet A (315–400nm), B (280–315nm) and C (100–280nm).

The major source of UVR is solar radiation or sunlight. Ultraviolet C (UV-C), from the sun, is virtually completely screened out by the Earth’s atmosphere, and is thus a negligible source of adverse human health effects. Ultraviolet B (UV-B) is responsible for erythema (sunburn), and associated with an increased risk of skin cancer, and immunosuppression. However, solar UV-B is crucial in the synthesis of vitamin D, which some recent studies suggest may potentially reduce risk of colon, prostate and breast cancers. Ultraviolet A (UV-A) contributes to skin aging and has more recently been implicated, along with UV-B, in the development of skin cancers in animals and in immunosuppression in humans. Although the sun is the main source of UV-A exposure, use of UV-A-emitting lamps in sunbeds for recreational tanning has raised concern about artificial sources of human exposure.

The International Agency for Research on Cancer has noted that there is sufficient evidence from studies in animals and in man to establish UVR as a human carcinogen (IARC 1992).2a For the most part, this review will focus on UVR as a single exposure without an attempt to separate the effects of the types noted above. This is because most of the human evidence concerning the health effects of UVR relates to reported sunlight exposure. When artificial sources of UVR are used in animal studies, distinguishing the separate effects of UV-A and UV-B is often possible. However, to date, this has not been possible in human epidemiological studies, most of which are retrospective and depend on subject recall. Animal studies will, in general, not be referred to in this review except where no alternative evidence is available.

Cancer and ultraviolet radiation

This review focuses initially on the positive relationship between UVR and the three major types of skin cancer: cutaneous malignant melanoma (CMM), basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). In addition, the potential relationship with cancer of the lip and with uveal (ocular) melanoma is discussed. Recent evidence has suggested a potential association between UVR and non-Hodgkin lymphoma. This hypothesis is examined, along with the hypothesis that solar exposure may reduce risk of colon, breast and prostate cancer through stimulation of increased serum vitamin D levels. Finally, all of the evidence is considered with a view to assessing the impact of UVR on the burden of cancer in Canada.

Cutaneous malignant melanoma

Solar ultraviolet radiation

The age-sex standardized incidence of CMM has increased markedly over the past 25 years in Canada (Gallagher et al., 1990; Gaudette and Gao, 1998)3,4a such that it represents significant health problem from a population health based perspective. Studies have revealed that the major environmental risk factor is solar and artificial UV exposure and that the principal modifying factor of this exposure is individual susceptibility as indicated by host pigmentation and sun sensitivity.

 Solar UVR exposure is estimated to account for about 93 percent of melanomas in Canada (Armstrong and Kricker, 1993).5a Early descriptive studies observed associations between the latitude of residence and melanoma incidence and mortality in Caucasian populations (Lancaster, 1956; Elwood et al., 1974; Fears et al., 1976).6,7,8 The association, however, was not as strong as might have been predicted were there a simple and direct relationship between total UVR exposure and melanoma incidence. This led investigators to hypothesize that the character and timing of exposure might be more relevant than total lifetime exposure in inducing CMM (Elwood and Hislop, 1982; Holman et al., 1983).9,10

Over the following 15 years, more than 25 case-control and cohort studies addressed this and other hypotheses concerning solar ultraviolet radiation; these studies have been evaluated in in the review of Elwood and Jopson (1997).11 Of the 29 studies outlined in Table 1, 22 evaluated at least one measure of intermittent solar exposure, usually defined as recreational time spent in the sun. A statistically significant positive association between intermittent exposure and melanoma risk was seen in 16 of the investigations (p<0.05). In contrast, chronic or constant solar exposure, usually defined as occupational in origin, was assessed in 20 studies, the majority demonstrating either no increased risk or a reduced risk in those with the highest levels. Total sun exposure was studied in 11 investigations, with an absence of an association in all but two (those of Grob et al.28a and Rodenas et al.39a), which observed increased risk of melanoma among those with higher exposures. Both of these studies, however, were conducted among Mediterranean subjects which differ from Canadians as they are, on average in high sunlight areas and possibly with respect to other risk factors for melanoma. Therefore, the extrapolation of these findings to the Canadian population is not straightforward.

Table 1
Summary of case-control studies on solar UV radiation exposure and cutaneous malignant melanoma
  OR (95% CI) in highest sun exposure category
Place of study Diagnosis years Overall no. cases/controls Intermittent Occupational Total Reference
Norway 1974-1975 78/131 2.4 (1.0-5.8) 1.4 (0.6-3.5) Klepp & Magnes 197912a
UK 1971-1976 111/342 1.5 (0.9-2.5) Adam et al. 198113
Scotland 1978-1980 113/113 0.6 (0.2-1.2) 0.4 (0.1-0.7) MacKie & Aitchison 198214
USA 1978-1979 111/107 2.5 (1.1-5.8) Lew et al. 198315
USA 1978-1981 114/228 2.4 (1.2-5.0) 1.6 (1.0-2.6) Rigel et al. 198316
Canada 1979-1981 595/595 1.7 (1.1-2.7) 0.9 (0.6-1.5) 1.2 (0.7-2.0) Elwood et al. 198517a
USA 1974-1980 404/521 0.7 (0.3-1.3) 0.6 (0.4-0.9) Graham et al. 198518
UK 1980-1982 58/333 6.5 (not given) Sorahan & Grimley 198519
USA 1972-1982 1 103/585 1.7 (1.2-2.3) 2.5 (1.4-4.4) 1.1 (0.8-1.6) Dubin et al. 198620a
UK 1981-1984 83/83 1.7 (0.3-8.6) Elwood et al. 198621a
Australia 1980-1981 511/511 1.1 (0.7-1.8) 0.7 (0.4-1.1) Holman et al. 198622a
Australia 1979-1980 183/183 1.9 (0.5-7.4) 2.3 (0.9-6.1) Green et al. 198623
Italy 1983-1985 103/205 0.9 (0.5-1.7) 0.6 (0.4-1.0) Cristofolini et al. 198724
Italy 1984-1986 208/416 2.1 (0.6-6.8) Zanetti et al. 198825
Denmark 1982-1985 474/926 1.8 (1.2-2.5) 0.7 (0.5-0.9) Osterlind et al. 198826a
Germany 1987 200/200 5.5 (1.2-25.3) Garbe et al. 198927
France 1986-1988 207/295 8.4 (3.6-19.7) 2.5 (1.2-5.1) 3.8 (2.2-6.5) Grob et al. 199028b
Sweden 1978-1983 523/505 1.8 (1.2-2.6) 0.6 (0.4-1.0) Beitner et al. 199029
USA 1979-1982 289/527 1.5 (1.0-2.4) 1.8 (0.9-4.0) 1.7 (1.1-2.8) Dubin et al. 199030
Italy 260/416 2.3 (1.4-3.8) Zanetti et al. 199231
USSR 3.4 (0.6-17.4) Zaridze et al. 199232
USA 1977-1979 324/415 2.0 (1.3-3.3) 0.7 (0.5-1.0) Herzfeld et al. 199333
Pan-European 1991-1994 420/447 6.1 (1.8-20.3) 0.3 (0.1-0.9) Autier et al. 199434
Netherlands 128/168 2.4 (1.3-4.2) Nelemans et al. 199435
USA 1984-1987 256/273 0.6 (0.3-1.2) 0.9 (0.5-1.6) White et al. 199436
Sweden 1988-1990 400/640 1.2 (0.8-1.8) 0.8 (0.6-1.0) Westerdahl et al. 199437a
USA 1981-1986 452/930 0.8 (0.6-1.1) 0.8 (0.5-1.5) Holly et al. 199538a
Spain 1988-1993 105/138 4.9 (2.2-10.9) 3.7 (1.7-7.5) 5.4 (2.4-12.0) Rodenas et al. 199639b
USA 1987-1989 548/494 H&N 2.6 (1.2-5.6) 0.5 (0.2-1.1) Chen et al. 199640
      UL 2.4 (1.2-4.8) 0.6 (0.2-1.1)    
      LL 2.7 (1.2-5.8) 0.3 (0.1-0.9)    
      T 2.7 (1.6-4.5) 0.9 (0.6-1.3)    

Table 1 adapted from Elwood and Jopson; Int J Cancer,1997;73:198-203.

OR = Odds ratio; 95% CI = 95% confidence intervals H&N = Head and Neck UL= Upper Limb LL = Lower Limb T = Trunk

With respect to other risk factors for melanoma, differences in the populations in which studies of sun exposure and melanoma are conducted can affect risk estimates because pigmentation factors render some individuals more susceptible to melanoma than others. Individuals with light skin, hair and eye colour were consistently found to be at elevated risk of CMM in virtually all case-control and cohort studies of this tumour in the early 1980s.12b-45 Furthermore, the propensity of the skin to burn—rather than tan—in the sun also consistently increases risk.20b,21b,43a-46 Finally, the presence of either freckling41,47a or acquired melanocytic nevi (skin moles) substantially increases risk,42a-44,47b,48 and at least one study reported a synergistic effect of these two factors.45

Overall, the results indicate that intermittent solar exposure is associated with an increased risk of melanoma in light-skinned populations, while constant or occupational exposure is associated with either no increase or a decrease in risk. Total solar exposure appears not to be associated with increased or decreased risk, except in Mediterranean populations, in which darker skin type may modify its effect. A cautious approach must be taken in interpreting the essentially negative findings for cumulative sun exposure. Most studies have been conducted in highly developed Western countries where indoor work predominates, effectively limiting the degree of cumulative exposure most people can accrue. Thus an effect for cumulative exposure might be missed due to limited range of exposure in these studies.

While the evidence indicates that the character of solar exposure is important in CMM, other findings, particularly those carried out in Australia, indicate that timing of exposure may also be important. Khlat et al.49a demonstrated that migrants arriving in Australia after the age of 15 from low sunlight areas, such as the UK, had substantially lower mortality from CMM than those who arrived at a younger age. Other studies demonstrate a substantially reduced risk for melanoma in individuals coming to Australia after age nine, when compared to those who are native born, even after controlling for lifetime exposure.43b,44 A US study showed that early life spent in high sunlight southern states conferred an increased adult melanoma risk even among subjects who had later moved to low sunlight states.50 Results of these investigations suggest that childhood may be a particularly susceptible period in relation to later risk of CMM.

In summary, as melanoma rates are substantially higher in white populations in high sunlight areas51a than in low sunlight areas, ambient levels of solar irradiance are clearly important in accounting for melanoma incidence. However, the analytic studies indicate that character and timing of exposure are also important, particularly in accounting for risk at the individual level. Armstrong52 has succinctly summarized the available information and hypothesized that for a particular intermittent pattern of exposure to solar UV, melanoma risk increases monotonically with increasing amount of exposure, and (for a given amount of exposure) risk of melanoma increases monotonically as exposure becomes more intermittent.

Recently, several studies have suggested that there may be at least two alternative etiologic pathways to melanoma.53-55 These studies are potentially very important as they suggest that the relationship between host susceptibility factors (skin colour, sun-sensitivity, nevus density, freckling density) and melanoma—and perhaps even the degree of solar exposure necessary for evolution of frank malignancy—may differ between the pathways. If this proves to be the case, it is likely that risk ratios associated with both susceptibility factors and solar exposure may have been substantially “diluted” in past epidemiologic studies due to inappropriate aggregation of etiologically distinct lesions.

Finally, a comparatively small proportion of malignant melanomas are due to what has been called either the atypical (dysplastic) nevus syndrome or familial atypical multiple mole-melanoma syndrome. Initially this was thought to be a phenotypic expression of a germline mutation predisposing to familial melanoma. More recently, a specific (CDKN2A) germline mutation on chromosome 9p21 has been found to be associated with melanoma in about 50 to 80 percent of families with very high incidence of melanoma.56,57 At the present time, these germline mutations are thought to be transmitted from one generation to another in an autosomal dominant pattern, with variable penetrance, and individuals with them appear to be at high risk for the disease. However, such mutations account for fewer than 10 percent of the melanomas, and as population-based rather than family-study-based data on the mutation becomes available, this estimate will undoubtedly decline further. Interestingly, the presence of CDKN2A mutations does not appear to materially affect the relationship between solar UV and melanoma risk in carriers.58 Reported family history of melanoma in a first degree relative (without testing for CDKN2A mutation) is only associated with approximately a twofold elevated risk of melanoma.59

Artificial ultraviolet radiation

A total of 14 studies have evaluated risk of melanoma in sunlamp and sunbed users,21c,22b,26b,37b,38b,46a,60-67 although the relatively minimal data presented in four of them preclude a proper interpretation of their results.21d,22c,46b,67 Table 2 presents selected results from the ten studies with relatively complete data. Because most of the studies conducted to date have small numbers of exposed subjects, they have limited statistical power. This has resulted in unstable risk ratios, with wide confidence intervals surrounding the risk estimates. Because of this, a recent meta-analysis was conducted in an attempt to summarize current knowledge.68a Ten studies provided estimates of risk for being exposed to sunbeds and sunlamps. Where possible, risk ratios adjusted for host susceptibility and sun exposure were used in the analysis. Compared to those with no exposure, those who had ever used sunlamps or sunbeds had a 25 percent increase in risk of CMM, which was statistically significant (95% CI: 1.05-1.49). Compared with subjects having no sunlamp or sunbed exposure, those with the “longest duration or highest frequency of exposure” had a relative risk of 1.61 (95% CI, 1.21-2.12). The analysis suggests that, overall, the existing body of epidemiological work indicates that use of sunbeds and sunlamps does increase risk of CMM.

Table 2
Summary of case-control and cohort studies of sunlamp or sunbed use and cutaneous malignant melanoma
Place of study Diagnosis years No. of cases/ controls Exposure Summary OR Reference
Eastern Denmark 1982-1985 474/926 Sunlamp and sunbed use 0.7 (0.5-1.0) Osterlind et al. 198826d
Scotland 1979-1984 180/197 Sunlamp and sunbed use 2.9 (1.3-6.4) Swerdlow et al. 198860b
Southern Ontario. Canada 1984-1990 583/608 Sunlamp and sunbed use Men: 1.9
Women: 1.5
(1.2-3.0)
(1.0-2.1)
Walter et al. 199061
Germany 1984-1987 856/705 Use of sunbeds 1.5 (0.9-2.4) Garbe et al. 199363
Pan-European 1991-1993 420/447 Sunlamp or sunbed use Overall: lamps:  1.3
Beds:  0.8
Tanning: lamps:  1.8
Beds:  1.0
(0.8-2.0)
(0.6-1.2)
(1.0-3.2)
(0.6-1.4)
Autier et al. 199462
Southern Sweden 1988-1990 400/640 Sunlamp or sunbed use Overall: 1.3 (0.9-1.8) Westerdahl et al. 199437c
California. USA 1981-1986 452/930 Sunlamp use 0.9 (0.7-1.2) Holly et al. 199538c
Connecticut. USA 1987-1989 624/512 Sunlamp use 1.13 (0.8-1.5) Chen et al. 199864
South Sweden 1995-1997 571/913 Sunbed use 1.2 (0.9-1.6) Westerdahl et al. 200065
Sweden and Norway 1991-1999 Total cohort 106.379 Sunbed and sunlamp use 1.55 (1.0-2.3) Veierod et al. 200366

OR = Odds ratio

Odds ratios presented are adjusted for other known melanoma risk factors (susceptibility and sun exposure) where such adjustment was carried out in the study.

Results of the meta-analysis must be interpreted with caution because there is likely to be at least some residual confounding due to host factors. Furthermore, individuals who use sunbeds to tan are also likely to engage in concomitant sunbathing. If this exposure is not adequately controlled for in the analyses, it is possible that the increased risk attributed to sunbed use may be explained in whole or in part by solar exposures. Finally, recreational exposure to artificial UV prior to the early 1980s entailed substantial UV-B exposure, whereas later (largely commercial) exposure was predominantly to UV-A. Thus, an analysis combining these exposures could conceivably be aggregating qualitatively different exposures. However, it should be noted that risk ratios from later studies do not appear to differ materially from those seen in earlier studies.

More research is necessary in this field to answer unresolved issues surrounding the relationship between artificial UV and CMM. Though contrary to some popular advertising, the body of available evidence does not suggest that artificial tanning reduces risk of CMM.

Solar UV-A

Solar UVR that reaches the Earth’s surface comprises approximately 95% UV-A and 5% UV-B: UV-C is completely filtered out by the Earth’s atmosphere.2b Recent studies using the Xiphophorus fish model have demonstrated that UV-A radiation is effective in inducing malignant melanoma in this species.69 In particular, melanoma induction showed particular sensitivity at the 365 and 405 nm wavelengths. Such findings have led to the suggestion that UV-A radiation may also induce CMM in humans.70 This has led other investigators to suggest that the advent of effective UV-B sunscreens in the 1960s, and their adoption for common use shortly thereafter, may have inadvertently fueled the increase in CMM incidence as a result of increased UV-A exposure.71 The authors propose that light-skinned individuals might expose themselves to the sun for much longer periods than previously because the onset of erythema is delayed by sunscreen use. This makes possible substantially more UV-A exposure in melanoma-susceptible individuals. A randomized trial conducted by Autier et al. tested the hypothesis that use of higher sun protection factor (SPF) sunscreens encourages longer exposure.72 Study subjects were randomized to unlabelled SPF 10 or SPF 30 sunscreen prior to vacation with instruction to use the sunscreen as needed and record time in the sun. Both groups used similar amounts of sunscreen, recorded similar sunburn patterns and similar mean vacation days, but subjects randomized to the SPF 30 compound spent significantly more time in the sun each day than those randomized to the lower SPF sunscreen. Thus, though there is some empirical evidence to support the notion that sunscreen use increases time in the sun, the findings apply as strongly to UV-B as to UV-A. It should be noted that the increase in incidence of CMM began prior to the advent of sunscreens,73 and that current incidence data suggest that age-standardized melanoma rates in young people are levelling off and perhaps beginning to decline.74 This trend is happening in the face of increasing popularity of very high SPF sunscreens, which should be allowing greater UV-A (and UV-B) exposure than ever.

Non-melanocytic skin cancer

Solar ultraviolet radiation

Ecological data collected in the US in the 1970s on the relationship between solar UVR and the two major forms of non-melanocytic skin cancer (NMSC), namely basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), indicated an incidence gradient from north to south within the country among the white population. This gradient correlated well with indices of UVR obtained using Robertson-Berger meters situated close to the areas where the cancer incidence information was collected.75 This close correlation reinforced the prevailing hypothesis that the two major forms of NMSC were directly related (in white individuals) to cumulative solar UV exposure. However, recent results from a number of well-conducted analytic studies (Table 3) suggest that the relationship of SCC and BCC to UVR is as complex as that seen for CMM.

Table 3
Summary of case-control and cohort studies of solar UV radiation and non-melanocytic skin cancer
  OR (95% CI) in highest sun exposure category
Place of study Diagnosis
years
Type of study No. of cases No. of
comparison subjects
Intermittent Occupational Total Reference
Canada 1977-1978 Case-control 92 174 SCC: 4.6 (0.58-36.53) SCC: 9.12 (0.99-84.47)   Aubrey & MacGibbon, 198576a
Australia 1987 Cross sectional 42 2,095 total subjects   SCC & BCC:1.76 (0.77-4.05)   Green et al. 198877
USA 1985-1986 Cross sectional 33 BCC
35 SCC
808 subjects   BCC: 1.11 (0.5-2.44)SCC: 2.53 (1.18-5.40)   Strickland et al. 198978
Vitasa et al. 199079
Canada 1988 Case-control 538 BCC 738   BCC: 1.29 (1.12-1.46)   Hogan et al. 198980
Australia 1985-1987 Cross sectional 66 BCC
21 SCC
1,770 sujets
au total
BCC: 0.6 (0.3-1.3)SCC: 3.9 (0.5-30.9) BCC: 1.3 (0.6-2.8)SCC: 5.5 (1.1-28.2)   Green & Battistutta, 199081
USA 1980-1984 Cohort 771 BCC 73,366
total cohort
    BCCe: ≈ 1.4 (calculated) Hunter et al. 199082
USA 1982-1990 Cohort 197 BCC 107,900
total cohort
    SCCf: ≈ 1.4 (calculated) Grodstein et al. 199583
Egypt 1991 Case-control 136 BCC & SCC 145   BCC and SCCb: 7.7 (4.0-14.6) BCC and SCCd6.1 (2.3-16.0) Khwsky et al. 199484a
Australia 1987 Case-control within a cohort 226 BCC 1,015 BCC: 3.86 (1.93-7.75)     Kricker et al. 199589a
Canada 1983-1984 Case-control 226 BCC
180 SCC
406 BCC: 2.6 (1.1-6.5)cSCC: 1.6 (0.6-4.5)c BCC: 1.4 (0.8-2.4)SCCa: 4.0 (1.2-13.1) BCC: 1.3 (0.7-2.4)SCC: 1.0 (0.4-2.1) Gallagher et al. 199590a,91a
Pan-European 1989-1993 Case-control 1,549 BCC
228 SCC
1,795 BCC: 1.47 (1.18-1.83)SCC: 0.63 (0.39-1.03) BCC: 0.84 (0.65-1.10)SCC: 1.60 (0.93-2.75)   Rosso et al. 199692a
Australia 1987 Case-control within a cohort 132 SCC 1, 031 SCC on usually exposed sites: 1.3 (0.57–2.90)
SCC on usually non-exposed sites 0.94 (0.36–2.60)
SCC on usually exposed sites: 1.3 (0.58–2.80)
SCC on usually non-exposed sites1.8 (0.55–5.60)
  English et al. 199893a

OR = Odds ratio; 95%; CI = 95% confidence intervals

a Occupational sunlight in the 10- years prior to diagnosis
b Outdoor vs. indoor occupation
c Recreational sunlight exposure age 0–19
d Heavy sun exposure vs. light exposure
e Subjects who used sunscreen and had 8 or more hours per week of sunlight compared to those with < 8 hours/week of exposure.
f Subjects who used sunscreen and had “regular time outdoors” compared to those without regular time outdoors.

Most studies76b-88 have used relatively simple questions to elicit information on solar exposure from subjects. Results from one study84b are difficult to interpret as BCC and SCC were combined in the analysis. In addition, the Egyptian population used in the study differs from other investigations in terms of pigmentary risk characteristics.

Later studies were designed specifically to separate the contributions of intermittent and constant solar exposure to risk, and appear to show differences between BCC and SCC.89b-93 Overall, the studies demonstrate little or no relationship between measures of intermittent recreational exposure and SCC, but significant associations with BCC. Indeed, the studies of Kricker et al.89c and Gallagher et al.90b both suggest a dose-response gradient in BCC risk with increasing exposure to recreational UVR, particularly in youth. For SCC, the weight of evidence appears to suggest that risk is related to measures of constant (occupational or cumulative) exposure. In the study of Gallagher et al.,91b this form of skin cancer is related to exposures in the ten years prior to diagnosis, while the Rosso et al.92b and English et al.93b studies indicate a relationship with longer-term occupational exposure.

While results of these studies require confirmation, it appears that cutaneous malignant melanoma and BCC share a number of similarities in their relationships with solar UVR. Both appear much more strongly related to measures of intermittent UV exposure, particularly in early life, than to measures of cumulative lifetime exposure. Squamous cell carcinoma appears to be different in that it owes more to constant or cumulative sun exposure than to intermittent exposure. In addition, there is as yet little evidence which has reported that sun exposure in childhood or youth is strongly related to this disease.

Artificial UV exposure

There have been few studies specifically addressing the potential relationship between sunbed and sunlamp use and risk of NMSC.76c,94a The few investigations conducted to date are summarized in Table 4. Overall, they indicate little increased risk, with the exception of the study of Aubrey and MacGibbon.76d However, the 13-fold increased risk of SCC seen in subjects using “long-tube sunlamps” is based on small numbers of study subjects, and so must be interpreted with caution. Well-conducted analytic studies with quantitative exposure data and good control for susceptibility factors and concomitant sun exposure are urgently needed to clarify risk.

Table 4
Summary of case-control or cross sectional studies of sunlamp & sunbed use and non-melanocytic skin cancer
Place of study Diagnosis years No. of
cases/controls
Exposure Summary OR in
highest exposure category (95% CI)
Reference
Canada 1977-78 92/174 Sunlamp use 13.42 (1.38-130.48) Aubrey & MacGibbon 198576e
Ireland Unknown 63 SCC & 58 BCC/121 Artificial sunlight 0.3 ns (calculated) O’Loughlin et al. 198585
Ireland 1984-85 396 BCC & SCC /396 Sunlamp & sunbeds 0.7 ns (calculated) Herity et al. 198986
Canada 1960s to 1980s 857/2,753 Medical phototherapy or sunbed use 1.33 (1.04-1.70) Hogan et al. 199187
USA 1980-86 1,805 Sunbathing or sunlamp use 1.04 (0.67-1.63) Karagas et al. 199288
Canada 1984-85 226 BCC & 180 SCC/406 Sunlamp use BCC: 1.2 (0.7-2.2)SCC: 1.4 (0.7-2.7) Bajdik et al. 199694b

OR = Odds ratio; 95% CI = 95% confidence intervals

Cancer of the lip

Cancer of the lip is rare in Canada and comprised only about 0.2 percent of cancers in females and 1.3 percent in males during the period 1984-1988, although by 2003 the rate in females had dropped to 0.1 percent and for males to 0.4 percent.95,96a The decline among males is likely due to the reduced rates of smoking and the continuing reduction in outdoor occupations.96b,97 Both male and female proportional declines are also likely influenced by increases in incidence at other cancer sites. Evaluation of incidence rates in this cancer is complicated by the fact that diagnoses are a mixture of neoplasms of the external lip and the oral cavity.2c Descriptive studies show that lip cancer is more common in males than females and that incidence rates are higher in light- than dark-skinned populations living in the same geographic area.51b Evaluation of mortality and incidence data from Australia show that rates of lip cancer are lower in migrants from low sunlight areas than they are in native-born Australians.98,99 This finding is suggestive of the pattern seen in malignant melanoma in Australia49b and may indicate the importance of sun exposure in youth for lip cancer.

Several studies have indicated that outdoor workers, such as farmers100-102 and fishermen,103 have elevated risks for lip cancer relative to the general male population or other males. A case-control study conducted in Los Angeles to evaluate risk factors associated with the sex differences in lip cancer incidence showed higher risk in those with fair complexion and in smokers.104a Increased risks were strongly related to lifetime solar exposure (Relative Risk [RR] highest quartile 13.5, 95% CI: 4.5-40.6) and to annual time spent outdoors. Among those with high lifetime sun exposure, the risk was twice as high in women using lip protection once per day or less than those using it at least twice per day. These findings suggest that the stronger association between UV and cancer incidence observed among men, relative to women, may be explained, in part, by the increased use of lip protection by women. In summary, lip cancer appears to be causally related to lifetime sun exposure.

Melanoma of the eye

Ocular melanoma is a rare condition with an incidence rate in Canada of about seven per million population.51c The rarity of this cancer has meant that few studies have been conducted and knowledge of the etiology is limited. Also, because subjects with this cancer are widely dispersed, the few studies have usually been restricted to telephone or postal questionnaires, which are probably inferior to in-person interviews for assessing important host susceptibility factors for melanoma.

The first case-control study105 evaluated cumulative solar exposure as well as intermittent and constant exposure, and reported no differences between cases and controls, although odds ratios were not presented in the paper and this study had limited statistical power (65 cases and 65 controls). The study did indicate that subjects with light skin and blue or grey eyes were at an elevated risk of uveal melanoma; similar findings were seen in later studies.106a-108

Tucker et al.106b found an elevated risk of ocular melanoma in subjects born in the southern US (and thus perhaps exposed to higher levels of UVR in youth) by comparison with those born in the north. The Tucker study found elevated odds ratios for subjects who reported gardening outdoors, but similar associations were not seen with other outdoor activities. No elevated risks for solar exposure were seen in Holly et al.107a as assessed by tendency to tan or sunburn and vacation and leisure-time activities.107b Seddon et al.108 compared 197 patients with ocular melanoma with 385 controls recruited through random digit dialling and found an elevated but non-statistically significant risk of ocular melanoma among subjects with the highest reported outdoor exposure, relative to those with the lowest.

More recent evidence for an association between ocular melanoma and UVR came from a study conducted in Australia. A national case-control study of ocular melanoma cases diagnosed between 1996 and mid-1998, with controls frequency matched by age and sex, demonstrated higher risks in subjects with grey, hazel or blue eyes.109 An increased risk of the cancer was found with increasing quartile of sun exposure up to 40 years of age (RR in highest quartile =1.8 ;95% CI: 1.1-2.8), after controlling for phenotype susceptibility factors.110 Interestingly, no indication of increased frequency of CDKN2A germline mutations was found in 62 ocular cases and their ethnically matched controls, suggesting that genetic predisposition is not the strong factor in ocular melanoma that it is in CMM.111

In general, evidence for associations between solar UVR and ocular melanoma has been weak to date. As the incidence of this cancer has not increased during the period in which cutaneous melanoma incidence has risen sharply, it seems unlikely that ocular melanoma will become a major public health hazard. Further studies of the relationship with solar UVR are unlikely to be productive until better measures of past solar exposure become available.

Three studies on sunlamp and sunbed use106c-108 have shown at least one measure of exposure to be related to increased risk of ocular melanoma; only two of these risk estimates are statistically significant. The exposure prevalence is very small, however, and these results should be interpreted cautiously. More studies with better quantitative data on artificial UV exposure are necessary before firm conclusions about a causal relationship can be reached.

Non-Hodgkin lymphoma

Solar ultraviolet radiation

Non-Hodgkin lymphoma (NHL) is the fifth most important cancer in Canada in terms of incidence.96c It is clear that the factors known to increase risk of NHL, including AIDS (Acquired Immune Deficiency Syndrome), can account for only a portion of the incidence rise112-113 seen over the past 20 to 30 years in this group of cancers.

Recently a number of investigators using descriptive data have suggested that sunlight exposure may be important in the etiology of NHL. This hypothesis is based on a number of lines of evidence. First, the increase in incidence of NHL roughly parallels the increases seen for CMM and NMSC.114a-115 This suggests that the factors known to be responsible for the increases in skin cancers may also be involved in NHL. The most significant factor for both CMM and NMSC is sunlight exposure.17b,22d,26c,46c,89d-93

The second line of evidence comes from parallel gradients of risk for NHL, CMM and SCC with proximity to the equator. Within the UK116 there is an incidence gradient for NHL, with higher rates in the south similar to that seen with CMM. Mean daily duration of bright sunlight in southern UK is 50 percent greater than in the north.117 Rates of NHL among countries in the northern hemisphere differ markedly; those whose population resides below 40 degrees north latitude have rates approximately 50 percent higher than those above 50 degrees north latitude.118 Using tables of ambient solar irradiation, McMichael and Giles plotted incidence rates of NHL from 49 cancer registries against ambient solar UVR. A strong, statistically significant correlation was seen between ambient solar irradiation determined by latitude of population residence and age-standardized incidence of NHL and of CMM. This relationship was similar in both males and females. The authors point out that no gradient is seen within some countries, such as Canada. However, as the majority of the Canadian population resides in close proximity to the country’s southern boundary, this is not unexpected. A separate study showed no latitude gradient in the US for NHL,119 but this was based on mortality data only, as incidence data were not available for the whole country.

A further line of evidence originates in studies of second primary tumours arising in cohorts of both NHL and skin cancer patients. Adami et al.114b showed a significantly increased risk of SCC (RR 5.5) and CMM (RR 2.8) among patients with NHL. In addition, an increased risk of NHL was seen in patients with prior SCC. In contrast to these findings, no other second primary tumours appeared to be elevated among the NHL and SCC cohorts, suggesting a similar causal agent in the two tumours. The authors noted the possibility of surveillance bias in the cohorts; however, the lack of elevated risk for other cancers argues against this explanation.

A further study carried out in Switzerland showed a twofold risk of subsequent NHL among a cohort of 11,878 BCC patients.120 Of interest is that significantly increased risks of similar magnitude were seen also for cancer of the lip, for SCC and for CMM, each of which (along with BCC) is known to be strongly related to sunlight exposure. No other cancer sites showed significantly increased incidence rates in the BCC cohort. It is possible that such increases in second primaries are due solely to an underlying immunosuppression among the cohorts. It has been shown that SCC and NHL are both more common in individuals who are immune compromised, such as kidney transplant patients and AIDS patients. However, as will be discussed, solar and artificial UVR have been demonstrated to cause immune suppression. This suppression has been suggested as one of the reasons, along with its ability to damage DNA, that UVR causes skin cancer. Furthermore, little evidence of an excess of CMM and cancer of the lip has been seen among patients immune compromised by renal transplantation or AIDS. This suggests that the independent effects of DNA damage and immune suppression from UV might be at work in the excess of NHL seen in cohorts of skin cancer patients.

Studies of migrants are often helpful in assessing the importance of environmental factors, as exposure often dramatically changes by comparison with the country of origin. Thus, data comparing NHL rates in migrants from low sunlight areas (such as the UK) to high sunlight areas (such as Australia and New Zealand) and vice versa are instructive with the caveat that changes in sunlight are likely accompanied with changes in diet (or other lifestyle factors) which may relevant to NHL. Cancer incidence data from Australia show that rates of NHL in migrants from the UK are similar to those of native-born Australians, and substantially higher than those of nationals remaining in the UK and Wales.121 The increase in risk for NHL in UK migrants is similar in magnitude to that seen for CMM. In UK migrants to New Zealand, a significant increased risk for NHL is seen in both males and females by comparison with their expected risk, based on rates in England and Wales.122 By contrast, New Zealand males and females migrating to the UK experienced reduced risks for NHL by comparison with their expected risk, based on rates seen in New Zealand.

Several studies have noted an increased risk of NHL among farmers.123 Although there is some evidence that this might be due to agricultural chemical use, the data are not compelling. Farmers also receive high cumulative solar UV exposures. Similarly, American soldiers having served in Vietnam have been reported by some—but not all—studies to have elevated rates of NHL.124-125 Although it has been suggested that this is due to exposures to herbicides, high sunlight exposure in Vietnam may have played a role.

The mechanism by which UVR might increase risk of NHL is through systematic immune supression. There is a substantial body of evidence that suggests that UVR causes significant changes in human immune status. Chronic high levels of UV-B exposure have been reported to be immunosuppressive through induction of suppressor T-cells.126 Hersey et al.127 have also reported that exposure of human volunteers to UV-A radiation for 30 minutes per day over a twelve-day period provoked a reduction in natural killer cell activity, with an accompanying decline in the number of such circulating cells. It is also known that T-lymphocytes are substantially more sensitive to the cell killing effects of UV-B than are fibroblasts.128 This indicates that, even at relatively low levels, an effect might be seen from UV exposure on the cells critical to human immune function. Granstein129 and Murphy et al.130 have also noted that fairly low doses of UVR result in depletion of epidermal Langerhans’ cells and in reduced levels of activity. Langerhans’ cells are important participants in the immune process as they present antigens to antibody producing cells in the body. Finally, there is animal evidence indicating that UVR produces suppressive effects on the immune systems of mice and impairs their ability to reject antigenic transplanted UV-related tumours,131-132 including melanoma.133 The evidence suggesting that UV-A might be nearly as effective as UV-B in inducing immune suppression could be particularly important, as use of UV-A sunbeds for tanning in Europe has increased rapidly in recent years, particularly among young people. It has been suggested that this could be related to the increases in NHL seen in Europe in young persons.134

Notwithstanding data from descriptive studies suggesting that sunlight exposure may be positively related to NHL, the evidence from carefully conducted case-control studies to date does not support this. A recently reported study in Australia found an inverse relationship between sun exposure and NHL.135a Similar results were seen in a Scandinavian study.136a After adjustment for potential confounders, a case-control study conducted in Sweden and Denmark also showed a reduced risk of NHL with increasing frequency of sun vacations abroad, and episodes of sunbathing at age 20 and 5 to 10 years prior to interview. A similar—though non-statistically significant association—was also detected for Hodgkin lymphoma. These results suggest that the increased frequency of skin cancer in those with prior NHL, and vice-versa, may not be related to UVR exposure, and also heighten the need for more studies of NHL, Hodgkin lymphoma and solar and artificial UV radiation.

Solar UVR and cancers of the colon, breast, ovary and prostate

Several review articles137,138 examining primarily laboratory evidence, and also some epidemiological findings, have suggested that sunlight exposure may exert a protective effect against a number of cancers including colon, prostate, breast and perhaps other female cancers. The suggested mechanism of action is that the active metabolite of vitamin D (1,25(OH)2D) inhibits proliferation and induces differentiation of cells that carry vitamin D receptors. This hypothesis is not new; in 1980, an ecological correlation study examining latitude of residence and colon cancer mortality found lower rates with declining latitude in North America.139a

The role of solar UV-B in stimulating vitamin D synthesis is thought to be a potential mechanism by which sunlight might affect incidence of these internal cancers. Although some vitamin D is taken in food, principally through consumption of fish, eggs and vitamin-D-enriched milk, most vitamin D is synthesized from 7-dehydrocholesterol in the skin under the influence of UV-B radiation in sunlight.140a It is then hydroxylated to 25(OH)D in the liver, and further, into biologically active 1,25(OH)2D in the kidney. As noted above, this metabolite acts like a hormone and is taken up by many organs in the body. Receptors for vitamin D are present in breast and prostate tissue.140b Furthermore, there is evidence that proliferation of cultured human prostate cancer,141,142 breast cancer,143a,144 and colon cancer cells145,146 are inhibited by Vitamin D. Finally, in vivo animal studies appear to show vitamin D induced inhibition of carcinogen induced colon147 and mammary tumours143b in rats.

Colon cancer

Garland and Garland139b noted that colon cancer death rates were lower in areas of the US with high solar UV levels than in low sunlight areas. They hypothesized that this finding might be due to sunlight’s ability to stimulate increased serum levels of vitamin D. A more detailed ecological correlation study which used incidence rates and also attempted some control for duration of residence in an area prior to diagnosis also found that risk of colon cancer appeared to be lower in high sunlight areas of the US.148 Bostick et al.,149 in an analysis of dietary intake among older women with colon cancer, found a modest protective effect for dietary calcium and vitamin D.

Intake of dietary vitamin D and calcium has been associated with lower risk of colon cancer and adenomatous polyps in a number of studies.150-152 However, in at least one of these studies, vitamin D consumption is highly correlated with multivitamin use and the attendant concern that the effect attributed to vitamin D may actually be due to another vitamin.152

Several cohort studies have shown a reduced risk of colon cancer in subjects with high serum vitamin D levels.153-158 A further investigation demonstrated a modest protective effect for high serum vitamin D, but only in certain sites in the colon.159

Not all studies of colon cancer and vitamin D have been positive. Several160,161 (including cohort studies) have shown either no protective effect or suggestion of an effect which is not strong enough to be statistically significant.162

At the present time there is strong suggestive evidence that vitamin D, perhaps in conjunction with calcium, may reduce the risk of colon cancer and its precursor lesion, adenomatous polyps. Most of this evidence is based on studies of dietary intake of the vitamin. There is little direct evidence showing that increased sunlight exposure reduces risk. Any evidence comes from ecologic correlation studies, a relatively weaker form than that which analytic studies might provide.

Breast and ovarian cancer

Gorham et al.163 examined mortality rates for breast cancer in the USSR and found the highest rates in the regions with the lowest sunlight levels. The relationship appeared to persist after an attempt to control for socio-economic factors, but no control was possible for ethnic and dietary factors. The association could have been due to other factors. Studies by Garland et al.164 and Freedman et al.165a also suggested that mortality from breast cancer is lower in areas of the world with more sun exposure. However, data from the Nurses’ Health study did not find a geographic gradient for breast cancer.166 Again, these studies are of the ecologic correlation variety and no actual measurements of sunlight exposure were made.

Analysis of data from the US National Health and Nutrition Examination Survey (NHANES) suggested that sunshine exposure may reduce risk of breast cancer (RR in highest sun exposure group relative to the lowest was 0.54, 95% CI: 0.28-1.02).167 The authors suggested that high serum levels of vitamin D, mediated through higher levels of sun exposure, might be responsible for this reduced risk. A further investigation carried out in Scandinavia suggested that women diagnosed with breast cancer in the summer months had longer survival than those diagnosed in winter.168a The authors suggested that this might be due to a beneficial effect of sunlight.

Case-control data from North Carolina showed significantly lower serum levels of 1,25 dihydroxy vitamin D in breast cancer cases than in controls.169 More recently, studies of dietary vitamin D have demonstrated that women with a high intake had lower risks of breast density170 and breast cancer.171 Neither of these examined exposure to UV radiation as a factor in vitamin D levels among the women.

Several studies of mortality from ovarian cancer165b,172 have demonstrated lower rates in high sunlight areas. The evidence for a protective effect of sunlight exposure in breast or ovarian cancer is, at present, modest. Furthermore, there is only scant evidence that either dietary intake of vitamin D, or serum levels of this vitamin, are associated with either cancer.

Prostate cancer

Several geographic studies of prostate cancer mortality in the US indicated decreased mortality in the southern US, consistent with an effect of sunlight exposure.165c,173 The authors hypothesized that the effect might be due to the effect of UVR on vitamin D production. Schwartz and Hulka noted an increased risk of prostate cancer in men with higher serum levels of vitamin D binding protein.174 A study of prediagnostic serum levels of vitamin D found a higher risk of prostate cancer in men with low levels of 1,25 dihydroxy vitamin D, although there was no difference for levels of 25 dihydroxy vitamin D.175 One further investigation showed similar results (Ahonen et al. 2000).176 Several other studies have shown no association between serum levels of vitamin D or its metabolites and subsequent risk of prostate cancer.177-181 The Scandinavian study noted earlier found a better prognosis in men diagnosed with prostate cancer in summer than in winter.168b A study of vitamin D receptor polymorphisms, vitamin D levels and prostate cancer among US physicians found little effect of different variants of the BsmI and TaqI polymorphisms on risk of prostate cancer.182

Two different investigations183a,184a conducted by John et al. have suggested a reduced risk of prostate cancer as sun exposure increases. The first, conducted using data from the NHANES I study, showed that inhabiting a more southernly located region of the US (rather than a northern one) might reduce risk of the disease.183b The second was a case-control study in which the ratio of skin reflectance on a sun-exposed site of the body (i.e., forehead), compared to that on a non-exposed site (i.e., upper underarm), served as a measure of sun exposure.184b However, it is possible that this metric is actually a better indicator of ability to tan vs burn in the sun, rather than a measure of solar exposure per se. A number of other sun exposure measures in the same study, showed little or no association with risk.

In summary, the results of studies linking sun exposure to subsequent risk of colon, prostate, breast and ovarian cancer have not yet demonstrated a convincing relationship between exposure and internal cancers. However, taken together, they do suggest a possible protective effect, at least for colorectal cancer, perhaps through the stimulation of higher serum levels of vitamin D. Many of the studies are descriptive or, if analytic, may suffer from incomplete control for confounders. The results from a recently published randomized clinical trial suggest that interventions designed to increase serum levels of vitamin D and calcium among post-menopausal women in order to reduce osteoporosis, might also reduce their risk of developing cancer (Lappe et al, 2007).185 However, it should be noted that the follow-up of the women in the trial was very short, providing insufficient study power to assess individual cancers. Furthermore, there was no intervention arm dedicated to vitamin D alone, and so it is difficult to determine the effects of the vitamin in the absence of supplemental calcium. Finally, the reduced incidence of cancer was achieved without increasing exposure to solar or artificial UV, and so it appears clear that the benefits might be realized without increasing risk of UV related diseases. More research is needed, and it is clearly inappropriate at this point in time to suggest that more solar exposure, particularly in fair-skinned populations, is a rational cancer prevention strategy.

Impact of UVR on cancer incidence and mortality in Canada

Attributable fraction

The impact of UVR-related cancer in Canada can be estimated through reference to incidence and mortality data. The major cancer types known to be related to solar or artificial UVR are CMM and NMSC, as well as cancer of the lip. It was estimated that in 2007, 4,600 new cases of melanoma would be diagnosed.96d In 2003 there were about 350 new cases of lip cancer.96e In addition, it was estimated that about 69,000 new cases of basal cell, squamous cell and other non-melanocytic skin lesions would be diagnosed. Armstrong and Kricker5b have estimated that about 93 percent of CMM in Canada can be attributed to solar UVR. It is likely that the figure for SCC and BCC would be very similar.

Deriving an estimate of the burden of skin cancers caused by artificial UVR, in particular that from sunbed and sunlamp use, is more difficult. Although a recent meta-analysis has shown a positive association between sunbed exposure and CMM, the odds ratios are relatively low for most users.68b Among those in the highest use categories, the risk ratios found in the meta-analysis are similar to those seen for reported sun exposure. However, with probable imperfect control for concomitant solar exposure, it is possible that at least some of the elevated risk in frequent users is due to outdoor sunbathing for tanning purposes. Marrett186 has estimated the population attributable risk for CMM due to sunlamp and sunbed use at between 6 and 15 percent if true relative risk is about 1.2, which is compatible with the aggregated data seen in the meta-analysis. Thus, if sunlamp and sunbed exposure is causally related to CMM, then combined with solar exposure, most of the CMM incidence seen today in this country can be attributed to one form or another of UVR.

The studies carried out to date do not allow an estimate to be made of the proportion of non-melanocytic skin cancer attributable to sunbed and sunlamp use.

The proportion of lip cancer attributable to sunlight exposure is difficult to estimate, as other factors such as pipe and cigarette smoking are also etiologically significant. However, the study of Pogoda et al.104b suggests that the use of lip covering (lipstick) among women more than once per day results in a 60 percent reduction in risk of the disease. It seems likely, then, that some 50 percent of the incident cases, probably in both sexes, are attributable to solar exposure. No studies have yet addressed the issue of artificial UV exposure and lip cancer risk, but the attributable fraction must be very small.

The original hypothesis that sunlight exposure might contribute to an increased incidence of non-Hodgkin lymphoma is of concern. However, the analytic studies conducted to date135b,136b appear to show a reduced—rather than increased—risk with high exposure. Further studies of a putative relationship are in the analysis phase and until the nature of the relationship is firmly established, no estimate can be made of the impact of UVR on the incidence or mortality of this disease.

Similarly, it is not possible to estimate the role of sunlight in the prevention of solid, internal cancers since a causal relationship has not been convincingly demonstrated. Further analytic studies are needed to illuminate the relationship between solar UV exposure, circulating vitamin D levels, and colon, prostate, and breast cancer.

In summary, some 4,500 life-threatening cancers per year are thought to be directly causally related to UVR, as well as some 64,000 less serious (basal and squamous cell) skin cancers and cancers of the lip. Melanoma of the eye, although very rare, is likely related to UVR, though its impact on the combined burden of cancer caused by UV radiation in Canada is probably negligible.

Primary prevention

Stern et al.187 estimated that consistent regular use of sunscreens in childhood (up to 18 years of age) might reduce non-melanocytic skin cancer incidence by 78 percent. This estimate is certainly optimistic for several reason: first, sunscreens have not been shown to reduce incidence of BCC (or cutaneous melanoma) in humans, although they do appear to be effective in preventing squamous cell carcinoma of the skin.188 Furthermore, the reduction is based on an estimated 80 percent of lifetime sunlight exposure occurring in childhood, which appears to be an unacceptably high estimate.189 Nevertheless, with appropriate clothing use, care not to sunburn and judicious use of sunscreens, it is likely that 50 percent of these tumours are preventable. A similar figure is likely possible for CMM. Lip cancer incidence in females is only one-fifth that in males, likely due to lower levels of chronic UV exposure, but also to use of lip protection (lipstick and other UV-screening lip balms). In addition, females smoke less than males and female pipe-smoking is virtually non-existent. It is likely that some 30-40 percent of male lip cancers are preventable as occupational solar exposure declines in men, although this is an estimate only.

Mortality

Deaths from non-melanoma skin cancers are rare, and official mortality statistics are likely to overestimate deaths from NMSC by nearly 60% (Lewis and Weinstock 2004)190a due to mistakes in completion of death registrations, or errors in cause of death coding. It is likely that no more than 100 deaths from SCC occur annually in Canada. In addition, there is evidence that many of the genuine NMSC deaths occur among individuals with comorbid psychiatric conditions,190b perhaps associated with extreme delay in seeking medical care for their lesions. It is unlikely that public health campaigns designed to reduce mortality from skin cancer would affect these deaths. Mortality from lip cancer is also low, probably not exceeding 20 deaths per year. Recent cancer mortality estimates suggest that some 900 deaths will occur from CMM each year in Canada.96f In total, then, probably about 850 to 870 deaths per year can reliably be attributed to UVR.

Secondary prevention

Most studies of CMM prognosis suggest that in lesions which are less than 0.76 mm in depth, mortality is only about five percent.191 Physician and public education programs have been shown to significantly reduce the proportion of melanomas which are deeply penetrating at diagnosis.192 Although declines in mortality from melanoma are being seen especially among the young in Canada,4b it is difficult to attribute the decline to early detection or education programs. A randomized clinical trial of early detection is necessary to evaluate whether routine screening for CMM is cost effective, and such a trial is beginning in Australia, a high incidence area. Even though Marrett et al.47c have shown that nearly 70 percent of melanomas could, in theory, be detected by screening only about 30 percent of the population in Canada, it is not clear that lay persons at high risk would be able to self-select for entry into a surveillance program. Even if subjects could self-select appropriately, screening 30 percent of the population of Canada on a continuing basis would be prohibitively expensive. Thus, the magnitude of melanoma mortality reduction possible with some form of self- or physician-conducted screening is not clear. As noted above, mortality from BCC and SCC is low in Canada and screening for these lesions would prevent few deaths.

Mortality reductions from lip cancer early detection programs implemented by dentists and oral hygiene practitioners are likely to be low. Given the costs involved, programs to detect ocular melanomas early would not produce worthwhile mortality reductions.

In summary, with our present state of knowledge, primary prevention manoeuvres aimed at more rational UV exposure are likely to be most effective in reducing the cancer burden from UVR in Canada. At the same time, more intensive research is needed to determine whether the incidence rates of other malignancies such as cancer of the colon, prostate, breast and ovary, as well as non-Hodgkin lymphoma are related, inversely or otherwise, to UV exposure.

References

  1. ^ World Health Organization. Environmental health criteria 160 ultraviolet radiation. Geneva: WHO; 1994.
  2. a,b,c IARC Monographs on the Evaluation of Carcinogenic Risks to Humans Vol. 55 Solar and Ultraviolet Radiation. Lyon : International Agency for Research on Cancer; 1992.
  3. ^ Gallagher RP, Ma B, McLean DI, et al. Trends in basal cell carcinoma, squamous cell carcinoma, and melanoma of the skin from 1973 through 1987. J Am Acad Dermatol 1990;23:413–21.
  4. a,b Gaudette L, Gao R-N. Changing trends in melanoma incidence and mortality. Health Rep 1998;10:29–41.
  5. a,b Armstrong BK, Kricker A. How much melanoma is caused by sun exposure? Melanoma Res 1993;3:395–401.
  6. ^ Elwood JM, Lee JA, Walter SD, et al. Relationship of melanoma and other skin cancer mortality to latitude and ultraviolet radiation in the United States and Canada. Int J Epidemiol 1974;3:325–32.
  7. ^ Fears TR, Scotto J, Schneiderman MA. Skin cancer, melanoma, and sunlight. Am J Public Health 1976;66:461–4.
  8. ^ Lancaster HO. Some geographical aspects of the mortality from melanoma in Europeans. Med J Aust. 1956;1082–7.
  9. ^ Elwood JM, Hislop TG. Solar radiation in the etiology of cutaneous malignant melanoma in Caucasians. Natl Cancer Inst Monograph 1982;62:167–71.
  10. ^ Holman CD, Armstrong BK, Heenan PJ. A theory of the etiology and pathogenesis of human cutaneous malignant melanoma. J Natl Cancer Inst 1983;71:651–6.
  11. ^ Elwood JM, Jopson J. Melanoma and sun exposure: an overview of published studies. Int J Cancer 1997;73:198–203.
  12. a,b Klepp O, Magnus K. Some environmental and bodily characteristics of melanoma patients. A case-control study. Int J Cancer 1979;23:482–6.
  13. ^ Adam S, Sheaves J, Wright N, et al. A case-control study of the possible association between oral contraceptives and malignant melanoma. Br J Cancer 1981;44:45–50.
  14. ^ MacKie RM, Aitchison T. Severe sunburn and subsequent risk of primary cutaneous malignant melanoma in Scotland. Br J Cancer 1982;46:955–60.
  15. ^ Lew RA, Sober AJ, Cook N, et al. Sun exposure habits in patients with cutaneous melanoma: a case-control study. J Dermatol Surg Oncol 1983;9:981–6.
  16. ^ Rigel DS, Friedman RJ, Levenstein MJ, et al. Relationship of fluorescent lights to malignant melanoma: another view. J Dermatol Surg Oncol 1983;9:836–8.
  17. a,b Elwood JM, Gallagher RP, Hill GB, et al. Cutaneous malignant melanoma in relation to intermittent and constant sun exposure: the Western Canada Melanoma Study. Int J Cancer 1985;35:427–33.
  18. ^ Graham S, Marshall J, Haughey B, et al. An inquiry into the epidemiology of melanoma. Am J Epidemiol 1985;122:606–19.
  19. ^ Sorahan T, Grimley RP. The aetiological significance of sunlight and fluorescent lighting in malignant melanoma: a case-control study. Br J Cancer 1985;52:765–9.
  20. a,b Dubin N, Momeson M, Pasternack BS. Epidemiology of malignant melanoma: pigmentary traits, ultraviolet radiation, and the identification of high-risk populations. Rec Results Cancer Res 1986;102:56–75.
  21. a,b,c,d Elwood JM, Williamson C, Stapleton PJ. Malignant melanoma in relation to moles, pigmentation, and exposure to fluorescent and other lighting sources. Br J Cancer 1986;53:65–74.
  22. a,b,c,d Holman CD, Armstrong BK, Heenan PJ. Relationship of cutaneous malignant melanoma to individual sunlight-exposure habits. J Natl Cancer Inst 1986;76:403–14.
  23. ^ Green A, Bain C, MacLennan R, et al. Risk factors for cutaneous melanoma in Queensland. Rec Results Cancer Res 1986;102:76–97.
  24. ^ Cristofolini M, Francheschi S, Tasin L, et al. Risk factors for cutaneous malignant melanoma in a northern Italian population. Int J Cancer 1987;39:150–4.
  25. ^ Zanetti R, Rosso S, Faggiano F, et al. A case-control study of melanoma of the skin in the province of Torino, Italy. Rev Epidemiol Sante Publique 1988;36:309–17.
  26. a,b,c,d Osterlind A, Tucker MA, Stone BJ, et al. The Danish case-control study of cutaneous malignant melanoma. II. Importance of UV light exposure. Int J Cancer 1988;42:319–24.
  27. ^ Garbe C, Kruger S, Stadler R, et al. Markers and relative risk in a German population for developing malignant melanoma. Int J Dermatol 1989;28:517–23.
  28. a,b Grob JJ, Gouvernet J, Aymar D, et al. Count of benign nevi as a major indicator of risk for nonfamilial nodular and superficial spreading melanoma. Cancer 1990;66:387–95.
  29. ^ Beitner H, Norell SE, Ringborg U, et al. Malignant melanoma: etiological importance of individual pigmentation and sun exposure. Br J Dermatol 1990;122:43–51.
  30. ^ Dubin N, Pasternack BS, Moseson M. Simultaneous assessment of risk factors for malignant melanoma and non-melanoma skin lesions with emphasis on sun exposure and related variables. Int J Cancer 1990;19:811–9.
  31. ^ Zanetti R, Francheschi S, Rosso S, et al. Cutaneous melanoma and sunburns in childhood in a southern European population. Eur J Cancer 1992; 28A:1172–6.
  32. ^ Zaridze D, Mukeria A, Duffy SW. Risk factors for skin melanoma in Moscow. Int J Cancer 1992;52:159–61.
  33. ^ Herzfeld PM, Fitzgerald EF, Hwang SA, et al. A case-control study of malignant melanoma of the trunk in white males in upstate New York. Cancer Detec Prev 1993;17(6):601–8.
  34. ^ Autier P, Dore J-F, Lejeune F, et al. Recreational exposure to sunlight and lack of information as risk factors for cutaneous malignant melanoma. Results of an EORTC case-control study in Belgium, France and Germany. Melanoma Res 1994;4:79–85.
  35. ^ Nelemans PJ, Rampen FHJ, Groenendal H, et al. Swimming and the risk of cutaneous melanoma. Melanoma Res 1994;4:281–6.
  36. ^ White E, Kirkpatrick CS, Lee JAH. Case-control study of malignant melanoma in Washington State. Am J Epidemiol 1994;139:857–68.
  37. a,b,c Westerdahl J, Olsson H, Masback A, et al. Use of sunbeds or sunlamps and malignant melanoma in Southern Sweden. Am J Epidemiol 1994;140:691–9.
  38. a,b,c Holly EA, Aston DA, Cress RD, et al. Cutaneous malignant melanoma in women. I. Exposure to sunlight, ability to tan, and other risk factors related to ultraviolet light. Am J Epidemiol 1995;141:923–33.
  39. a,b Rodenas JM, Delgado-Rodriguez M, Herranz MT,et al. Sun exposure, pigmentary traits and risk of cutaneous malignant melanoma: a case-control study in a Mediterannean population. Cancer Causes Control 1996;7:275–83.
  40. ^ Chen Y, Dubrow R, Holford TR, et al. Malignant melanoma risk factors by anatomic site: a case-control study and polychotomous logistic regression analysis. Int J Cancer 1996;67:636–43.
  41. ^ Elwood JM, Gallagher RP, Hill GB, et al. Pigmentation and skin reaction to sun as risk factors for cutaneous malignant melanoma: Western Canada Melanoma Study. Br Med J 1984;288:99–102.
  42. ^ Green A, MacLennan R, Siskind V. Common acquired nevi and the risk of malignant melanoma. Int J Cancer 1985;35:297–300.
  43. a,b Holman CD, Armstrong BK. Pigmentary traits, ethnic origin, benign nevi, and family history as risk factors for cutaneous malignant melanoma. J Natl Cancer Inst 1984;72:257–66.
  44. ^ Holman CD, Armstrong BK. Cutaneous malignant melanoma and indicators of total accumulated exposure to the sun: an analysis separating histologic type. J Natl Cancer Inst 1984;73:75–82.
  45. ^ Osterlind A, Tucker MA, Hou-Jensen K, et al. The Danish case-control study of cutaneous malignant melanoma. I. Importance of host factors. Int J Cancer 1988;42:200–6.
  46. a,b,c Gallagher RP, Elwood JM, Hill GB. Risk factors for cutaneous malignant melanoma: the Western Canada Melanoma Study. Rec Results Cancer Res 1986;102:38–55.
  47. a,b,c Marrett LD, King WD, Walter SD, et al. Use of host factors to identify people at high risk of cutaneous malignant melanoma. Can Med Assoc J 1992;147:445–53.
  48. ^ Holly EA, Kelly JW, Shpall SN, et al. Number of melanocytic nevi as a major risk factor for malignant melanoma. J Am Acad Dermatol 1987;17:459–68.
  49. a,b Khlat M, Vail A, Parkin DM, et al. Mortality from melanoma in migrants to Australia: variation by age at arrival and duration of stay. Int J Cancer 1992;135:1103–13.
  50. ^ Mack TM, Floderus B. Malignant melanoma risk by nativity, place of residence at diagnosis, and age at migration. Cancer Causes and Control 1991;2:401–11.
  51. a,b,c Parkin DM, Whelan SL, Ferlay J, et al. Cancer Incidence in Five Continents Volume VII. IARC Scientific Publication No. 143. Lyon : Centre international de recherche sur le cancer; 1997.
  52. ^ Armstrong BK. Epidemiology of malignant melanoma: intermittent or total accumulated exposure to the sun? J Dermatol Surg Oncol 1988;14:835-49.
  53. ^ Whiteman DC, Watt P, Purdie DM, Hughes MC, Hayward NK, Green AC. Melanocytic nevi, solar keratoses, and divergent path-ways to cutaneous melanoma. JNCI 2003;95:806-812.
  54. ^ Purdue MP, From L, Kahn HJ, Armstrong BK, Kricker A, Gallagher RP, McLaughlin JR, Klar NS, Marrett LD. Etiologic factors associated with p53 immunostaining in cutaneous malignant melanoma. Int J Cancer 2005;117(3):486-93.
  55. ^ Siskind V, Whiteman DC, Aitken JF, Martin NG, Green AC. An analysis of risk factors for cutaneous melanoma by anatomical site (Australia). Cancer Causes and Control 2005;16:193-199.
  56. ^ Cannon-Albright LA, Meyer LJ, Goldgar DE, et al. Penetrance and expressivity of the chromosome 9p melanoma susceptibility locus (MLM). Cancer Res 1994;54:6041–4.
  57. ^ Goldstein AM, Fraser MC, Clark WH Jr., et al. Age at diagnosis and transmission of invasive melanoma in 23 families with cutaneous malignant melanoma/dysplastic nevi. J Natl Cancer Inst 1994;86:1385–90.
  58. ^ Goldstein AM, Falk RT, Fraser MC, et al. Sun-related risk factors in melanoma-prone families with CDKN2A mutations. J Natl Cancer Inst 1998;90;709–10.
  59. ^ Ford D, Bliss JM, Swerdlow AJ, et al. Risk of cutaneous melanoma associated with a family history of the disease. Int J Cancer 1995;62:377–81.
  60. a,b Swerdlow AJ, English JS, MacKie RM, et al. Fluorescent lights, ultraviolet lamps and risk of cutaneous melanoma. Br Med J 1988;297:647–50.
  61. a,b Walter SD, Marrett LD, From L. The association of cutaneous malignant melanoma with the use of sunbeds and sun-lamps. Am J Epidemiol 1990;131:232–43.
  62. ^ Autier P, Joarlette M, Lejeune F, et al. Cutaneous malignant melanoma and exposure to sunlamps and sunbeds: an EORTC multicentre case-control study in Belgium, France and Germany. Int J Cancer 1994;58:809–13.
  63. ^ Garbe C, Weiss J, Kruger S, et al. The German Melanoma Registry and environ-mental risk factors implied. Recent Results Cancer Res 1993;128:69-89.
  64. ^ Chen Y-T, Dubrow R, Zheng T, Barnhill RL, Fine J, Berwick M. Sunlamp use and risk of cutaneous malignant melanoma; a population-based case-control study. Int J Epidemiol 1998;27:758-65.
  65. ^ Westerdahl J, Ingvar C, Masback A, Jonsson N, Olsson H. Risk of cutaneous malignant melanoma in relation to use of sumbeds: further evidence for UV-A carcinogenicity. Br J Cancer 2000;82:1593-9.
  66. ^ Veierod MB, Weiderpass E, Thorn M, et al. A prospective study of pigmentation, sun exposure, and risk of cutaneous malignant melanoma in women. JNCI 2003; 95:1530-8.
  67. ^ MacKie RM, Freudenberger T, Aitchison TC. Personal risk-factor chart for cutaneous melanoma. Lancet 1989;2:487-90.
  68. a,b Gallagher RP, Spinelli JJ, Lee TK. Tanning beds sunlamps and risk of cutaneous malignant melanoma. Cancer Epidemiol Biomarkers and Prev 2005;14:562-6.
  69. ^ Setlow RB, Grist E, Thompson K, et al. Wavelengths effective in induction of malignant melanoma. Proc Natl Acad Sci 1993;90:6666–70.
  70. ^ Setlow RB, Woodhead AD. Temporal change in the incidence of malignant melanoma: explanation from action spectra. Mutation Res 1994;307:365–74.
  71. ^ Garland CF, Garland FC, Gorham ED. Rising trends in melanoma: an hypothesis concerning sunscreen effectiveness. Ann of Epidemiol 1993;3(1):103–10.
  72. ^ Autier P, Dore J-F, Negrier S, Lienard D, Panizzon R, Lejeune FJ, et al. Sunscreen use and duration of sun exposure: a double-blind randomized trial. JNCI 1999;91:1304-1309.
  73. ^ Osterlind A, Jensen OM. Trends in the incidence of malignant melanoma of the skin in Denmark, 1943–1982. Recent Res Cancer Res 1986;102:8–17.
  74. ^ Gallagher RP, Phillips N, Coldman AJ, et al. Future trends in the incidence of cutaneous malignant melanoma in white populations. In Altmeyer P, Hoffman K, Stucker M, Editors. Skin Cancer and UV Radiation. Berlin: Springer Verlag;1997. p. 501–6.
  75. ^ Scotto J, Fears TR, Fraumeni J. Incidence of non-melanoma skin cancer in the United States. U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, National Cancer Institute. NIH Publication No. 83–2433; April 1983.
  76. a,b,c,d,e Aubrey F, MacGibbon B. Risk factors of squamous cell carcinoma of the skin. A case-control study in the Montreal region. Cancer 1985;55:907–1011.
  77. ^ Green A, Beardmore G, Hart V, et al. Skin cancer in a Queensland population. J Am Acad Dermatol 1988;19:1045–52.
  78. ^ Strickland PT, Vitasa BC, West SK, et al. Quantitative carcinogenesis in man: ultraviolet B dose dependence of skin cancer in Maryland watermen. J Natl Cancer Inst 1989;81:1910–3.
  79. ^ Vitasa BC, Taylor HR, Strickland PT, et al. Association of nonmelanocytic skin cancer and actinic keratosis with cumulative solar ultraviolet exposure in Maryland watermen. Cancer 1990;65:2811–7.
  80. ^ Hogan DJ, To T, Gran L, et al. Risk factors for basal cell carcinoma. Int J Dermatol 1989;28:591–4.
  81. ^ Green A, Battistutta D. Incidence and determinants of skin cancer in a high-risk Australian population. Int J Cancer 1990;46:356–61.
  82. ^ Hunter DJ, Colditz G, Stamfer M, et al. Risk factors for basal cell carcinoma in a prospective cohort of women. Ann Epidemiol 1990;1:13–23.
  83. ^ Grodstein F, Speizer FE, Hunter DJ. A prospective study of incident squamous cell carcinoma of the skin in the Nurse’s health study. J Natl Cancer Inst 1995;87:1061–6.
  84. a,b Khwsky FE, Bedwani R, D’Avanzo B, et al. Risk factors for non-melanomatous skin cancer in Alexandria, Egypt. Int J Cancer 1994;56:375–8.
  85. ^ O’Loughlin C, Moriarty MJ, Herity B, et al. A re-appraisal of risk factors for skin carcinoma in Ireland. A case-control study. Irish J Med Sci 1985;154:61–5.
  86. ^ Herity B, O’Loughlin G, Moriarty MJ, et al. Risk factors for non-melanoma skin cancer. Irish Med J 1989;82(4):151–2.
  87. ^ Hogan DJ, To T, Wilson ER, et al. A study of acne treatments for the skin of the head and neck. Br J Dermatol 1991;125:343–8.
  88. ^ Karagas MR, Stuckel T, Greenberg R, et al. Risk of subsequent basal cell carcinoma and squamous cell carcinoma of the skin among patients with prior skin cancer. J Am Med Assoc 1992;267:3305–9.
  89. a,b,c,d Kricker A, Armstrong BK, English DR, et al. Does intermittent sun exposure cause basal cell carcinoma? A case-control study in Western Australia. Int J Cancer 1995;60:489-94.
  90. a,b Gallagher RP, Hill GB, Bajdik CD, et al. Sunlight exposure, pigmentary factors, and risk of non-melanocytic skin cancer. I. Basal cell carcinoma. Arch Dermatol 1995;131:157-63.
  91. a,b Gallagher RP, Hill GB, Bajdik CD, et al. Sunlight exposure, pigmentation factors, and risk of nonmelanocytic skin cancer. II. Squamous cell carcinoma. Arch Dermatol 1995;131:164-9.
  92. a,b Rosso S, Zanetti R, Martinez C, et al. The multicentre south European study ‘Helios’ II: different sun exposure patterns in the etiology of basal cell and squamous cell carcinomas of the skin. Br J Cancer 1996;73:1447-54.
  93. a,b English DR, Armstrong BK, Kricker A, et al. Case-control study of sun exposure and squamous cell carcinoma of the skin. Int J Cancer 1998;77:347-53.
  94. a,b Bajdik CD, Gallagher RP, Astrakianakis G, et al. Non-solar ultraviolet radiation and risk of basal and squamous cell skin cancer. Br J Cancer 1996;73:1612–4.
  95. ^ Band PR, Gaudette LA, Hill GB, et al. The making of the Canadian cancer registry: cancer incidence in Canada and its regions, 1969-1988. Minister of Supply and Services 1993; Catalogue No. C52-42/1992.
  96. a,b,c,d,e,f National Cancer Institute of Canada. Canadian Cancer Statistics 2007; Toronto (Canada): National Cancer Institute of Canada, 2007. http://www.cancer.ca
  97. ^ Gallagher RP, Elwood JM, Yang CP. Is chronic sunlight exposure important in accounting for increases in melanoma incidence? Int J Cancer 1989;44:813-5.
  98. ^ Armstrong BK, Woodings TL, Stenhouse NS, et al. Mortality in migrants to Australia 1962-1971. Perth: University of Western Australia; 1983.
  99. ^ McCredie M, Coates MS. Cancer Incidence in Migrants to New South Wales: 1972-1984; New South Wales Cancer Registry, 1989. Woolloomooloo (NSW): 1989; New South Wales Cancer Council. p. 22-23; 62-3.
  100. ^ Gallagher RP, Threlfall WJ, Jeffries E, et al. Cancer and aplastic anemia in British Columbia farmers. J Natl Cancer Inst 1984;72:1311-5.
  101. ^ Olsen JH, Jensen OM. Occupation and risk of cancer in Denmark. An analysis of 93,810 cancer cases, 1970-1979. Scand J Work Environ Health 1987;13 Suppl 1:1-91.
  102. ^ Wiklund K, Dich J. Cancer risks among male farmers in Sweden. Eur J Cancer Prev 1995;4:81-90.
  103. ^ Spitzer WO, Hill GB, Chambers LW, et al. The occupation of fishing as a risk factor in cancer of the lip. New Engl J Med 1975;293:419-24.
  104. a,b Pogoda JM, Preston-Martin S. Solar radiation, lip protection and lip cancer risk in Los Angeles County. Cancer Causes Control 1996;7:458-63.
  105. ^ Gallagher RP, Elwood JM, Rootman J, et al. Risk factors for ocular melanoma: Western Canada Melanoma Study. J Natl Cancer Inst 1985;74:775-8.
  106. a,b,c Tucker MA, Shields JA, Hartge P, et al. Sunlight exposure as risk factor for intraocular melanoma. New Engl J Med 1985;313:789-92.
  107. a,b Holly EA, Aston DA, Char DH, et al. Uveal melanoma in relation to ultraviolet light exposure and host factors. Cancer Res 1990;50:5773-7.
  108. ^ Seddon JM, Gragoudas ES, Glynn RJ, et al. Host factors, UV radiation, and risk of uveal melanoma. Arch Ophthalmol 1990;108:1274-80.
  109. ^ Vajdic CM, Kricker A, Giblin M, McKenzie J, Aitken J, Giles G, Armstrong BK. Eye colour and cutaneous nevi predict risk of ocular melanoma in Australia. Int J Cancer 2001;92:906-12.
  110. ^ Vajdic CM, Kricker A, Giblin M, McKenzie J, Aitken J, Giles G, Armstrong BK. Sun exposure predicts risk of ocular melanoma in Australia. Int J Cancer 2002;101:175-82.
  111. ^ Vajdic C, Kricker A, Duffy DL, Aitken JF, Stark M, ter Huurne J, Martin NG, Armstrong BK, Hayward NK. Ocular melanoma is not associated with CDKN2A or MC1R variants-a population-based study. Melanoma Res 2003;13:409-13.
  112. ^ Devesa SS, Fears T. Non-Hodgkin’s lymphoma time trends: United States and international data. Cancer Res 1992;52 Suppl;5432–40.
  113. ^ Holford TR, Zheng T, Mayne S, et al. Time trends of non-Hodgkin’s lymphoma: are they real? What do they mean? Cancer Res 1992;52 Suppl:5443–6.
  114. a,b Adami J, Frisch M, Yuen J, et al. Evidence of an association between non-Hodgkin’s lymphoma and skin cancer. Br Med J 1995:1491–5.
  115. ^ Cartwright R, McNally R, Staines A. The increasing incidence of non-Hodgkin’s lymphoma (NHL): the possible role of sunlight . Leuk Lymph 1994;14(5–6):387–94.
  116. ^ Bentham G. Association between incidence of non-Hodgkin’s lymphoma and solar ultraviolet radiation in England and Wales. Br Med J 1996;312:1128–31.
  117. ^ Swerdlow A, Dos Santos Silva I. Atlas of Cancer Incidence in England and Wales 1968–1985. Oxford: Oxford University Press; 1994.
  118. ^ McMichael AJ, Giles GG. Have increases in solar ultraviolet exposure contributed to the rise in incidence of non-Hodgkin’s lymphoma? Br J Cancer 1996;73:945–50.
  119. ^ Hartge P, Devesa SS, Grauman D, et al. Non-Hodgkin’s lymphoma and sunlight. J Natl Cancer Inst 1996;88:298–300.
  120. ^ Levi F, LaVecchia C, Van-Cong T, et al. Incidence of invasive cancers following basal cell skin cancer. Int J Cancer 1998;147:722–6.
  121. ^ Giles GG, Farrugia H, Silver B, et al. Cancer in Victoria 1982–1987. Melbourne: Anti-Cancer Council of Victoria; 1992.
  122. ^ Swerdlow AJ, Cooke KR, Skegg DCG, et al. Cancer incidence in England and Wales and New Zealand and in migrants between the two countries. Br J Cancer 1995;72:236–43.
  123. ^ Blair A, Zahm SH. Cancer among farmers. J Occup Med 1991;6:335–54.
  124. ^ Boyle CA, Decoufle P, O’Brien TR. Long term health consequences of military service in Vietnam. Epidemiol Rev 1989;2:1–27.
  125. ^ O’Brien TR, Decoufle P, Boyle CA. Non-Hodgkin’s lymphoma in a cohort of Vietnam veterans. Am J Public Health 1991;81:758–60.
  126. ^ Hersey P, Haran G, Hasic E, et al. Alteration of T-cell subsets, and induction of suppresion T-cell activity in normal subjects after exposure to sunlight. J Immunol 1983;31:171–4.
  127. ^ Hersey P, MacDonald M, Henderson C, et al. Suppression of natural killer cell activity in humans by radiation from solarium lamps depleted of UV-B. J Invest Dermatol 1988;90:305–10.
  128. ^ Arlett FE, Lane JE, Harcourt SA, et al. Hypersensitivity of human lymphocytes to UV-B and solar irradiation. Cancer Res 1993;53:1–6.
  129. ^ Granstein RD. Ultraviolet radiation effects on immunologic function. Regional Immunol 1990;3(2):112–19.
  130. ^ Murphy G, Morris P, Young A, et al. Low dose ultraviolet B radiation depletes human epidermal Langerhans cells. Br J Dermatol 1993;129:674–7.
  131. ^ Fisher MS, Kripke ML. Systematic alteration induced in mice by UV irradiation and its relationship to UV carcinogenesis. Proc Natl Acad Sci USA 1977;74:1688–92.
  132. ^ Willis I, Menter JM, Whyte HJ. The rapid induction of cancers in the hairless mouse utilizing the principle of photoaugmentation. J Invest Dermatol 1981;76:404–8.
  133. ^ Wolfe P, Donawho CK, Kripke ML. Effect of sunscreens on UV radiation induced enhancement of melanoma growth in mice. J Natl Cancer Inst 1994;86:99–105.
  134. ^ Hjalgrim H, Frisch M, Begtrup K, et al. Recent increase in the incidence of non-Hodgkin’s lymphoma among young men and women in Denmark. Br J Cancer 1996;73:951–4.
  135. a,b Hughes AM, Armstrong BK, Vajdic CM, Turner J, Grulich AE, Fritschi L, Milliken S, Kaldor J, Benke G, Kricker A. Sun exposure may protect against non-Hodgkin lymphoma: a case-control study. Int J Cancer 2004;112:865-71.
  136. a,b Smedby KE, Hjalgrim H, Melbye M, Torrang A, Rostgaard K, Munksgaard L, Adami J, Hansen M, Porwitt-MacDonald A, Jensen BA, Roos G, Pedersen BB, Sundstrom C, Glimelius B, Adami H-O. Ultraviolet radiation exposure and risk of malignant lymphomas. JNCI 2005;97:199-209.
  137. ^ Ainsleigh HG. Beneficial effects of sun exposure on cancer mortality. Prev Med 1993;22:132–40.
  138. ^ Studzinski GP, Moore DC. Sunlight—can it prevent as well as cause cancer? Cancer Res 1995;55:4014–22.
  139. a,b Garland CF, Garland FC. Do sunlight and vitamin D reduce the likelihood of colon cancer? Int J Epidemiol 1980;9:227–31.
  140. a,b Webb AR, Holick MF. The role of sunlight in the cutaneous production of Vitamin D3. Annual Rev Nutr 1988;8:375–99.
  141. ^ Miller GJ, Stapleton GE, Ferrara JA, et al. The human prostatic cell line LNCaP expresses biologically active specific receptors for 1 alpha,25-dihydroxyvitamin D3. Cancer Res 1992;52:515–20.
  142. ^ Skowronski RJ, Peehl DM, Feldman D. Vitamin D and prostate cancer: 1,25 dihydroxyvitamin D3 receptors and actions in human prostate cancer cell lines. Endocrinology 1993;132:1952–60.
  143. a,b Colston KW, MacKay AG, James SY, et al. EB1089: a new vitamin D analogue that inhibits the growth of breast cancer cells in-vivo and in-vitro. Biochem Pharmacol 1992;44:2273–80.
  144. ^ Frampton RJ, Omond SA, Eisman JA. Inhibition of human cancer cell growth by 1,25-dihydroxyvitamin D3 metabolites. Cancer Res 1983;43:4443–7.
  145. ^ Cross HS, Huber C, Peterlik M. Antiproliferative effect of 1,25-dihydroxyvitamin D3 and its analogs on human colon adenocarcinoma cells (CACO-2): influence of extracellular calcium. Biochem Biophys Res Commun 1991;179:57–62.
  146. ^ Thomas MG, Tebbutt S, Williamson RCN. Vitamin D and its metabolites inhibit cell proliferation in human rectal mucosa and a colon cancer cell line. Gut 1992;33:1660–3.
  147. ^ Pence BC, Budding F. Inhibition of dietary fat-promoted colon carcinogenesis by supplemental calcium or vitamin D3. Carcinogenesis 1988;9:187–90.
  148. ^ Emerson JC, Weiss NS. Colorectal cancer and solar radiation. Cancer Causes Control 1992;3:95–9.
  149. ^ Bostick RM, Potter JD, Sellers TA, et al. Relation of vitamin D, and dairy food intake to incidence of colon cancer among older women: the Iowa Women’s health study. Am J Epidemiol 1993;137:1302–17.
  150. ^ Lieberman DA, Prindiville S, Weiss DG, Willett W. Risk fators for advanced colonic neoplasia and hyperplastic polyps. JAMA 2003;290:2959-67.
  151. ^ Marcus PM, Newcomb P. The association of calcium, vitamin D and colon and rectal cancer in Wisconsin women. Int J Epidemiol 1998;27:788-93.
  152. ^ White E, Shannon JS, Patterson RE. Relationship between vitamin and calcium supplement use and colon cancer. Cancer Epi Biomarkers Prev 1997;6:769-774.
  153. ^ Garland C, Barrett-Connor E, Rossof AH, et al. Dietary vitamin D and calcium and risk of colorectal cancer: a 19 year prospective study in men. Lancet 1985;I:307-9.
  154. ^ Garland CF, Comstock GW, Garland FC, et al. Serum 25-dihydroxyvitamin D and colon cancer: eight-year prospective study. Lancet II 1989;1176-8.
  155. ^ Tangrea J, Helzlsouer K, Pietinen P, Taylor P, Hollis B, Virtamo J, Albanes D. Serum levels of vitamin D metabolites and the subsequent risk of colon and rectal cancer in Finnish men. Cancer Cause Control 1997;8:615-25.
  156. ^ Kearney J, Giovannucci E, Colditz G, Stampfer M, Hunter DJ, Speizer F, Wing A, Willett W. Calcium, vitamin D, and dairy foods and the occurrence of colon cancer in men. Am J Epidemiol 1996;143:907-17.
  157. ^ Martinez ME, Giovannucci E, Colditz G, Stampfer M, Hunter DJ, Speizer F, Wing A, Willett. Calcium vitamin D and the occurrence of colon cancer among women. JNCI 1996;88:1375-1382.
  158. ^ Feskanich D, Ma J, Fuchs CS, Kirkner GJ, Hankinson SE, Hollis BW, et al. Plasma vitamin D metabolites and risk of colorectal cancer in women. Cancer Epidemiol Biomarkers and Prev 2004;13:1502-8.
  159. ^ Platz EA, Hankinson S, Hollis B, Colditz G, Hunter DJ, Speizer FE, Giovannucci E. Plasma 1,25 dihydroxyvitamin and 25 hydroxyvitamin D and adenomatous polyps of the distal colorectum. Cancer Epidemiol Biomarkers and Prev 2000;9:1059-65.
  160. ^ Braun MM, Helzlsouer K, Hollis B, Comstock G. Colon cancer and serum vitamin D metabolite levels 10-17 years prior to diagnosis. Am J Epidemiol 1995:142:608-11.
  161. ^ Lin J, Zhang SM, Cook NR, Manson J, Lee I-M. Intakes of calcium and vitamin D and risk of colorectal cancer in women. Am J Epidemiol 2005;161:755-64.
  162. ^ Kampman E, Slattery M, Caan B, Potter JD. Calcium vitamin D sunshine exposure dairy products and colon cancer risk (United States). Cancer Causes Control 2000;11:459-66.
  163. ^ Gorham ED, Garland FC, Garland CF. Sunlight and breast cancer incidence in the U.S.S.R. Int J Epidemiol 1990;19:820–4.
  164. ^ Garland CF, Garland FC, Gorham ED. Calcium and vitamin D. Their roles in colon and breast cancer prevention. Ann NY Acad Sci 1999;889:107-19.
  165. a,b,c Freedman DM, Dosemeci M, McGlynn K, Sunlight and mortality from breast ovarian colon and prostate and non-melanoma skin cancer; a composite death certificate, case-control study. Occup Environ Med 2002;59:257-62.
  166. ^ Laden F, Spiegelman D, Neas LM et al. Geographic variation in breast cancer incidence rates in a cohort of US women. JNCI 1997;89:1373-1378.
  167. ^ John EM, Schwartz GG, Dreon D, et al. Vitamin D and breast cancer risk: the NHANES I epidemiologic follow-up study, 1971-1975 to 1992. Cancer Epidemiol Biomarkers Prev 1999;8:399-406.
  168. a,b Robsahm TE, Tretli S, Dahlback A, Moan J. Vitamin D3 from sunlight may improve the prognosis of breast, colon, and prostate cancer (Norway). Cancer Cause Cont 2004;15:149-58.
  169. ^ Janowsky EC, Lester G, Hulka B. Vitamin D and breast cancer [abstract]. Proceedings of the Department of Defense Breast Cancer Research Program Meeting. 1997 Oct 31–Nov; Washington D. C., (Vol III) p. 999–1000.
  170. ^ Berube S, Diorio C, Verhoek-Oftedahl W, Brisson J. Vitamin D, calcium and mammographic densities. Cancer Epidemiol Biomarkers and Prev 2004;13:1466-72.
  171. ^ Shin M-H, Holmes MD, Hankinson SE, Wu K, Colditz GA, Willett WC. Intake of dairy products and vitamin D and risk of breast cancer JNCI 2002;94:1301-11.
  172. ^ Lefkowitz ES, Garland CF. Sunlight, vitamin D, and ovarian cancer mortality rates in U.S. women. Int J Epidemiol 1994;23:1133–6.
  173. ^ Hanchette CL, Schwartz GG. Geographic patterns of prostate cancer mortality. Evidence for a protective effect of ultraviolet radiation. Cancer 1992;70(12):2861–9.
  174. ^ Schwartz GC, Hulka BS. Is vitamin D deficiency a risk factor for prostate cancer? [hypothesis]. Anticancer Res 1990;10:1307-11.
  175. ^ Corder EH, Guess HA, Hulka BS, et al. Vitamin D and prostate cancer: a prediagnostic study with stored sera. Cancer Epidem Biomarker Prev 1993;2:467–72.
  176. ^ Ahonen MH, Tenkanen L, Teppo L, Hakama M, Tuohimaa P. Prostate cancer risk and prediagnostic serum 25-hydroxyvitamin D levels (Finland). Cancer Cause Cont 2000;11:847-52.
  177. ^ Gann PH, Ma J, Hennekens CH, et al. Circulating vitamin D metabolites in relation to subsequent development of prostate cancer. Cancer Epidemiol Biomarkers and Prev 1996;5:121–6.
  178. ^ Nomura AMY, Stemmerman GN, Lee J, Kolonel LN, Chen TC, Turner A, Holick MF. Serum vitamin D metabolite levels and subsequent development of prostate cancer. (Hawaii, USA). Cancer Causes Control 1998;3:425-32.
  179. ^ Platz EA, Leitzmann MF, Hollis BW, Willett WC, Giovannucci E. Plasma 1,25 dihydroxy and 25 hydroxyvitamin D and subsequent risk of prostate cancer. Cancer Causes Control 2004;15:255-65.
  180. ^ Braun MM, Helzlsouer K, Hollis BW, Comstock GW. Prostate cancer and prediagnostic levels of serum vitamin D metabolites (Maryland, USA). Cancer Causes Control 1995;6:235-9.
  181. ^ Chan JM, Giovannucci E, Andersson S-O, Yuen J, Adami H-O, Wolk A. Dairy products, calcium, vitamin D and risk of prostate cancer (Sweden). Cancer Causes Control 1998;9(6):559-66.
  182. ^ Ma J, Stampfer M, Gann P, Hough HL, Giovannucci E, Kelsey KT, Hennekens CH, Hunter DJ. Vitamin D polymorphisms, circulating vitamin D metabolites and risk of prostate cancer in United States physicians. Cancer Epidemiol Biomarkers Prev 1998;7:385-90.
  183. a,b John EM, Dreon D, Koo J, Schwartz GG. Residential sunlight exposure is associated with a decreased risk of prostate cancer. J Steroid Biochem Mol Med 2004;89-90:549-52.
  184. a,b John EM, Schwartz GG, Koo J, Van Den Berg D, Ingles SA. Sun exposure vitamin D receptor gene polymorphisms and risk of advanced prostate cancer. Cancer Res 2005;65:5470-9.
  185. ^ Lappe JM, Travers-Gustafdon D, Davies KM, Recker RR, Heaney RP. Vitamin D and calcium supplementation reduces cancer risk: results of a randomized trial. Am J Clin Nutr 2007; 85:1586-1591.
  186. ^ Marrett LD. Non-solar sources of ultraviolet radiation and cutaneous malignant melanoma: a review of the evidence. In Gallagher RP, Elwood JM, [editors]. Epidemiological aspects of cutaneous malignant melanoma. Boston: Kluwer Academic Publishers; 1994. p. 107–30.
  187. ^ Stern RS, Weinstein MC, Baker SG. Risk reduction for non-melanoma skin cancer with childhood sunscreen use. Arch Dermatol 1986;122:537–45.
  188. ^ International Agency for Research on Cancer. IARC Handbooks on Cancer Prevention. Vol 5 Sunscreens. IARC Lyon, 2001.
  189. ^ Godar DE. UV doses of American children and adolescents. Photochem Photobiol 2001;74:787-93.
  190. a,b Lewis KG, Weinstock MA. Nonmelanoma skin cancer mortality (1988-2000): the Rhode Island follow-back study. Arch. Dermatol 2004;140:837-842.
  191. ^ Soong S-J, Weiss HL. Predicting outcome in patients with localized melanoma. In Balch CM, Houghton A, Sober AJ, Soong S-J (eds) Cutaneous Melanoma Quality Medical Publishing, St. Louis, 1998.
  192. ^ MacKie RM, Hole D. Audit of public education campaign to encourage earlier detection of malignant melanoma. Br Med J 1992;304:1012–5.
Report a problem or mistake on this page
Please select all that apply:

Thank you for your help!

You will not receive a reply. For enquiries, contact us.

Date modified: