ARCHIVED - Chronic Diseases in Canada
Volume 29 · Supplement 1 · 2010
Cancer and the environment: Ten topics in environmental cancer epidemiology in Canada
Shirley A. Huchcroft, Yang Mao and Robert Semenciw, Editors
A work of this magnitude requires the help of many people who deserve special thanks. The chapter on pesticides benefitted from the editorial assistance of Wendy Thompson, Brenda Branchard and Grace Alessi. The chapter on the pulp and paper industry relied heavily on the literature review portion of a grant application prepared by Colin L Soskolne, Steve E Hrudey, Tee L Guidotti, Shirley M Fincham and Kay E Teschke. Contributions by Stephen Gabos and Agneta Hollander in the preparation of that grant application are recognized also. The glossary required the concerted efforts of Urmil (Kitty) Chugh, who prepared the initial draft, Judith Hall, who provided advice on the organic chemistry components, and Kevin Hall, who acted as a consultant with respect to the geology terminology.
We are grateful to our French translators, Lise Talbot-Bélair, Louise Filteau and Alfred Schertz, and to our French reviewers, Ulrick Auguste, Susan Cook, Marie DesMeules, Claudia Lagacé, Patrick Levallois, Pierre Phillipe, Marie-Claude Rousseau and Anne-Marie Ugnat. A content review by members of the Healthy Environments and Consumer Safety Branch of Health Canada and Paul Villeneuve of the Department of Public Health Sciences at the University of Toronto was also very much appreciated, as was a review of the radiation sections by staff members of the Canadian Nuclear Safety Commission.
Sue Price formatted early versions of the document and provided numerous checks along the way. James Hutchenreuther and Urmil Chugh assisted with reference numbering, and Robert Semenciw reviewed various drafts with patience and attention to detail. Mary Hodges did the lion’s share of final document formatting and preparation.
Regarding specific chapters, Dr. Kay Teschke provided helpful feedback on an earlier draft of the chapter on pulp and paper mills.
This Chronic Diseases in Canada supplement is a compilation of literature reviews by scientific experts. It was initiated as follow-up to the Green Plan, the federal government’s environmental agenda in the 1990s. In recognizing that Canadians are concerned about the environment and its relationship to their health, this document attempts to address some of these concerns in relation to cancer by reviewing and summarizing the epidemiological literature for ten environmental exposures, and highlighting future research needs. The topics include three types of radiation exposure (ultraviolet, radon and electromagnetic (powerfrequency electromagnetic fields)), three classes of chemical exposure (organochlorines, disinfection by-products, and pesticides), two types of air pollution (environmental tobacco smoke and outdoor air pollution), and two industrial sources (pulp and paper milling, and metal mining and processing).
This publication is intended to provide a base of information for researchers interested in environmental cancer epidemiology and to assist with the formulation of research priorities. The ten topics reviewed here were selected because concern about them has been expressed or because they involve known animal carcinogens. Complete elimination of exposures to carcinogens in the environment, synthetic or natural, is not technically feasible if cancer can potentially occur at any level of exposure (i.e., the linear non-threshold theory). Consequently, it is important to have an operational concept of safety which is more practical than that of zero risk. Such an approach uses the concept of acceptable or essentially negligible risk to determine the exposure levels at which carcinogens are regulated.1a Acceptable risk has been defined as one that is “so small, whose consequences are so slight, or whose associated benefits (perceived or real) are so great that persons or groups in society are willing to take or be subjected to that risk”. The level of risk where remedial action is recommended will vary according to the “agent or process being regulated, the economic and social costs and benefits and technology factors”.1b-3
In accordance with the system used by the International Agency for Research on Cancer (IARC) to assess the strength of the evidence for human carcinogenicity,4a the ten exposures reviewed here can be grouped into three broad categories, with some exposures occupying more than one and the first category—human carcinogens—should be subdivided. Tables 1-4 refer to these categories. For many of the exposures discussed here, ongoing etiological research awaits methods development, particularly in exposure assessment.
I Human carcinogens
a) Exposures for which estimated attributable numbers of cancers are cause for concern
The epidemiological evidence is adequate to conclude that ultraviolet radiation, environmental tobacco smoke and radon are human carcinogens, and to estimate the number of cancer cases and deaths attributable to them at typical exposure levels (Table 1).
|Exposure||Most likely cancer sites||Estimated attributableannuallya||Comment|
|Ultraviolet radiation||Skin and lip||70,000b||450||Solar UVR is the major environmental risk factor for skin and lip cancers. Phenotype and exposure factors, such as age, intensity and duration, affect risk.|
|Environmental tobacco smoke||Lung||280c||252||Environmental tobacco smoke is considered a causal agent in lung cancer. The estimated numbers are for non-smoking Canadians exposed to environmental tobacco smoke.|
|Radon||Lung||1,589||1,430c||Radon is a cause of lung cancer.|
Approximately 69,000 Canadians are diagnosed with non-melanoma skin cancer each year, making it the most common form of cancer, and about 350 are diagnosed with lip cancer.5a Approximately 94% percent of all new cases of skin cancer are basal or squamous cell, with malignant melanoma accounting for the remaining 6 percent. Exposure to solar ultraviolet radiation is likely responsible for over 90 percent of skin cancer in Canada and for more than half of lip cancer.6,7 Malignant melanoma is the most serious of the skin cancers and accounts for approximately 4,600 cases and 900 deaths in Canada each year.5b Death from non-melanoma skin cancer and lip cancer is rare. It is estimated that approximately 450 UVR-related cancer deaths yearly (one half the total UVR-related deaths) are preventable by reducing sun exposure.
Environmental tobacco smoke
Tobacco smoke is the major component of indoor air pollution. Recent research suggests that each year about 250 non-smoking Canadians die of lung cancer caused by prolonged exposure to other people’s tobacco smoke.8 A recent meta-analysis (i.e., systematic summary of studies) estimated the risk of lung cancer among non-smoking women as 24 percent higher for those living with a smoker than for those not, and 39 percent higher for those exposed to ETS in the workplace. Because of the large number of Canadians who have never smoked but have been exposed to second-hand smoke regularly over a number of years as a child, as a spouse and/or in the workplace, the risk associated with exposure has significant public health implications.
Radiation from radon gas is carcinogenic to humans.9 Most of the evidence for carcinogenicity has been obtained from studies of miners exposed to high concentrations; however, radon exposure at levels to which many Canadians are routinely exposed have also been found to increase the risk of lung cancer. Radon has been estimated to be responsible for over fifteen hundred cases of lung cancer a year in Canada (about 8% of lung cancer cases).10 A number of techniques are available to homeowners to reduce radon concentrations in their homes.
b) Exposure levels that result in small increases in risk
For three exposures—selected organochlorine insecticides, outdoor air pollution and some nickel species—the accumulated evidence suggests that typical Canadian exposure levels result in small increases in risk (Table 2). To estimate the number of cases of cancer that can be attributed to an exposure, it is necessary to know the prevalence of the exposure and the magnitude of the risk. There is only limited evidence regarding the prevalence of exposure to these agents in the Canadian population. As well, much evidence of their carcinogenicity comes from occupational studies, where exposures are much higher than those experienced by the general Canadian population. The nature of the exposure-response relationships at low exposure levels is unclear, making it inappropriate to attempt to quantify the cancer burden in the Canadian population which can be attributed to their exposures. In addition, it has been difficult to control for potential confounding factors.
|Exposure||Most likely cancer sites||Comment|
|Organochlorine insecticides||Sarcoma, lymphoma, leukemia||Many of the organochlorine insecticides used in Canada in the past are now considered to be known or suspected animal carcinogens. The limited epidemiological evidence regarding a number of organochlorine insecticides generally supports the toxicological evidence of an association with cancer.|
|Air pollution||Lung||Slightly increased risks of lung cancer are associated with exposure to highly polluted air. In general, air pollution in Canada is not severe enough to pose a significant cancer threat.|
|Nickel mining and processing||Respiratory||Risks are related primarily to high levels of exposure to certain nickel compounds encountered in the work environment in the past. The general population risk from the extremely small concentrations detectable in ambient air is negligible.|
The limited epidemiological evidence regarding a number of organochlorine insecticides and several cancers generally supports the toxicological evidence of an association with cancer. Because of these concerns and others, and with the exception of lindane, which is permitted for the treatment of head lice as a pharmaceutical, organochlorine insecticides are no longer marketed in Canada.
The most commonly measured outdoor air pollutants in Canada include particulates, ground-level ozone, carbon monoxide, sulphur dioxide and oxides of nitrogen. These substances are the principal ingredients of precursors of smog and acid rain.2 Some particulates are small enough to be inhaled and deposited in the lungs. Some studies suggest that long-term, regular exposure to particulate matter is associated with increased risk of lung cancer.11 In Western industrialized countries that have pollution regulations, air pollution poses only a small risk for developing cancer. Further research is a priority to better control residual confounding from cigarette smoking (active and passive), and more accurately assign air pollution exposures.
Nickel mining and processing
IARC has concluded that there is sufficient evidence in humans for the carcinogenicity of nickel sulphate and the combinations of nickel sulphides and oxides encountered in the nickel refining industry. Furthermore, there is sufficient evidence in experimental animals to conclude that metallic nickel is possibly carcinogenic to humans.12 Some early studies of nickel workers in the early half of the 20th century revealed higher-than-expected rates of various cancers of the respiratory tract. Since then, exposure levels to workers have been reduced to the point where there is little or no detectable risk in most sectors of the nickel industry. The general population risk from the extremely small concentrations of nickel compounds detectable in ambient air is negligible.
II Exposures for which the epidemiological evidence of carcinogenesis in humans is limited
According to the IARC classification, limited evidence of carcinogenicity in humans means that a positive association has been observed between exposure and cancer for which a causal interpretation is credible, but chance, bias or confounding cannot be ruled out with reasonable confidence.4b Limited evidence exists for three of the ten exposures reviewed here (Table 3).
|Exposure||Most likely cancer sites||Comment|
|Dioxins||Soft-tissue sarcoma, non-Hodgkin's lymphoma, Hodgkin's disease||For specific groups of organochlorines, the epidemiological evidence of an association with specific cancers is sufficient to warrant concern, such as dioxins and soft-tissue sarcoma, non-Hodgkin's lymphoma and Hodgkin's disease. Toxicological studies have demonstrated that 2,3,7,8-Tetrachlorodibenzo-para-dioxin (TCDD) is carcinogenic.|
|Electromagnetic fields||Leukemia||Some studies of high exposures suggest an association with leukemia; however, others show no such association. There is inadequate evidence that residential exposures to electric or magnetic fields are associated with increased cancer risks for adults. In particular, evidence is inconclusive as to whether living close to a source of EMF (e.g., power lines) increases one's risk of developing cancer.|
|Phenoxy herbicides||Non-Hodgkin's lymphoma and soft-tissue sarcoma||Epidemiological studies suggest associations with phenoxy herbicides; however, this finding is not supported by the toxicological evidence obtained using animal studies.|
Polychlorinated dibenzo-para-dioxins (PCDDs)—a class of organochlorines—are formed as inadvertent by-products during the production of chlorophenols and chlorophenoxy herbicides and have been detected as contaminants of these products. Dioxins may also be produced in thermal processes such as incineration and metal-processing, and the bleaching of paper pulp with free chlorine. Dioxins have been related sufficiently to specific cancers such as soft-tissue sarcoma, non-Hodgkin’s lymphoma and Hodgkin’s disease, to warrant further research. This judgement is based on consistency of findings across studies, the magnitude of the risk estimates and absence of major sources of bias. Toxicological studies have demonstrated the carcinogenicity of 2,3,7,8-tetrachlorodibenzo-para-dioxin, but other dioxins are not classifiable as to their carcinogenicity.13
Pesticides encompass many classes of chemicals that share the ability to kill or otherwise control pests. Many are rated as possible or probable human carcinogens. Epidemiological studies suggest that phenoxy herbicides may be associated with non-Hodgkin’s lymphoma and soft-tissue sarcomas; however, this finding is not supported by the toxicological evidence. IARC has concluded that there is limited evidence that phenoxy acid herbicides as a group are carcinogenic in humans, with inadequate evidence of carcinogenicity in animals.14 This position was based on the class of chemicals which included the more highly contaminated 2,4,5-T and “may not apply to individual chemicals within the group”. The United States Environmental Protection Agency (US EPA) considers 2,4-D is not classifiable as to human carcinogenicity.15 However, both the US EPA and the Canadian Pest Management Regulatory Agency have recently concluded that the domestic use of one of the most commonly used phenoxy herbicides, 2,4-D, does not entail an unacceptable risk of harm to human health.
Electric and magnetic fields, both of which are forms of non-ionizing radiation, are ubiquitous in Canada. Sources include electrical equipment, power lines and household appliances. IARC rates extremely low-frequency magnetic fields as possibly carcinogenic to humans and extremely low-frequency electric fields as not classifiable as to their carcinogenicity to humans. There is limited evidence in humans for the carcinogenicity of extremely low-frequency magnetic fields in relation to childhood leukemia.16
III Exposures for which the epidemiological evidence is inadequate for assessing carcinogenicity in humans
In IARC’s classification, inadequate epidemiological evidence means that the available studies are of insufficient quality, consistency or statistical power to permit a conclusion regarding the presence or absence of a causal association between exposure and cancer, or no data on cancer in humans are available (Table 4).4c
|Exposure||Most likely cancer sites||Comment|
|Disinfection by-products||Bladder||The sum of evidence, especially from studies with the most detailed exposure assessments, supports a modest increase in risk of bladder cancer after many years of exposure. However, toxicological data do not support the magnitude of risk observed in epidemiological studies.|
|Pulp and paper milling||Various||Several compounds found in bleached pulp mill effluent are mutagenic and have been identified as mammalian carcinogens in laboratory studies. Studies of both workers and communities nearby pulp and paper mills have failed to produce conclusive results.|
|Gold and copper mining and processing||Lung and stomach||Some associations between lung and stomach cancer and gold and copper mining were found primarily in early studies of workers before the introduction of methods to reduce dust exposure. Conclusions linking cancer to exposures in gold and copper mining and processing are not possible.|
To prevent water-borne diseases, most municipal Canadian water supplies are disinfected with chlorine. During water disinfection, chlorine reacts with organic material in the water, producing a number of by-products, including trihalomethanes (THMs). Several studies of cancer incidence in human populations have reported associations between long-term exposure to high levels of disinfection by-products and increased risk of bladder and possibly colon cancer. However, toxicological studies do not support the magnitude of risk observed in the epidemiological studies. A recent summation of the toxicological and epidemiological evidence can be accessed via the Web site of the WHO International Programme on Chemical Safety (IPCS).17 IARC rates chlorinated drinking water as not classifiable as to its carcinogenicity to humans because the evidence for carcinogenicity in both humans and experimental animals is considered inadequate.18
The pulp and paper industry
Although several chlorinated organic compounds found in bleached pulp mill effluent are mutagenic and proven carcinogens in mammals, epidemiological studies of pulp and paper mill workers and nearby communities have failed to produce conclusive results. IARC rates exposures from pulp and paper manufacture as not classifiable as to their carcinogenicity to humans.19
Gold and copper mining
Conclusions linking cancer to exposures generated by gold and copper mining and processing are not yet possible.
No single epidemiological study should be expected to provide the definitive answer regarding the carcinogenic potential of an environmental exposure. Thus, despite the often large number of studies reviewed, the need for further research is a recurring theme for most of the topics examined here. However, the types of research required differ across exposures. For ultraviolet radiation and environmental tobacco smoke, risk-reduction research as well as etiological research into other cancer sites is called for. For the three exposures that result in small increases in risk at typical exposure levels for Canadians (organochlorine insecticides, air pollution and nickel mining and processing), ongoing monitoring of exposure levels is important. For those exposures where the potential to cause cancer in humans is still in question, etiological research is a priority. For many of these exposures, further etiological research awaits methods-development research, particularly in relation to exposure assessment.
- ^ Health Canada and Atomic Energy Control Board. Assessment and management of cancer risks from radiological and chemical hazards. Ottawa: Minister of Public Works and Government Services Canada; 1998.
- ^ Health Canada. Health and environment. Ottawa: Minister of Public Works and Government Services Canada; 1997.
- ^ Health and Welfare Canada. Risk Management in the Health Protection Branch. Ottawa: Minister of Supply and Services; 1990.
- a,b,c Preamble to the IARC monograph programme on the evaluation of carcinogenic risks to humans. Lyon : Centre international de recherche sur le cancer; 1999. URL : http://monographs.iarc.fr/monoeval/eval.html
- a,b,c,d National Cancer Institute of Canada. Canadian cancer statistics 2007. Toronto: NCIC; 2007. Available at: http://www.cancer.ca
- ^ Armstrong BK, Kricker A, How much melanoma is caused by sunlight exposure? Melanoma Res 1993:3:395–401.
- ^ Pogoda JM, Preston-Martin S. Solar radiation, lip protection, and lip cancer in Los Angeles County women. Cancer Causes Control 1996;7:458–63.
- ^ Baliunas D, Patra J, Rehm J, Popova S, Kaiserman M, Taylor B. Smoking-attributable mortality and expected years of life lost in Canada 2002: Conclusions for prevention and policy. Chronic Dis Can 2007;27(4):154-62.
- ^ Atomic Energy Control Board. Canada: living with radiation. Ottawa: Minister of Supply and Services Canada; 1995.
- ^ Chen J, Tracy BL. Canadian Population Risks of Radon Induced Lung Cancer. Rev can thérapie respir; Automne 2005 : [19-27].
- ^ Health Canada. It’s your health. A fact sheet series produced by Health Canada’s Environmental Health Program: Smog and your health. Available at:
- ^ IARC monograph programme on the evaluation of carcinogenic risks to humans: nickel and nickel compounds. Lyon: International Agency for Research on Cancer; 1997. Available at: http://monographs.iarc.fr/ENG/Monographs/vol49/volume49.pdf
- ^ IARC monograph programme on the evaluation of carcinogenic risks to humans: polychlorinated dibenzo-para-dioxins. Lyon:International Agency for Research on Cancer; 1997. Available at: http://monographs.iarc.fr/ENG/Monographs/vol69/volume69.pdf
- ^ IARC monograph programme on the evaluation of carcinogenic risks to humans: chlorphenoxy herbicides. Lyon: International Agency for Research on Cancer; 1998. Available at: http://monographs.iarc.fr/ENG/Monographs/suppl7/suppl7.pdf
- ^ U.S.Environmental Protection Agency. Reregistration Eligibility Decision for 2,4-D. EPA 738-R-05-002. June 2005. Available at: http://www.epa.gov/REDs/24d_red.pdf
- ^ IARC monograph programme on the evaluation of carcinogenic risks to humans: static and extremely low-frequency (ELF) electric and magnetic fields. Lyon: International Agency for Research on Cancer; 2002. Available at: http://monographs.iarc.fr/ENG/Monographs/vol80/index.php
- ^ WHO International Programme on Chemical Safety. Available at: www.who.int/pcs/ehc/summaries/ehc_216.html
- ^ IARC monograph programme on the evaluation of carcinogenic risks to humans: chlorinated drinking water. Lyon: International Agency for Research on Cancer; 1997. Available at: http://monographs.iarc.fr/ENG/Monographs/vol52/volume52.pdf
- ^ IARC monograph programme on the evaluation of carcinogenic risks to humans: pulp and paper manufacture. Lyon: International Agency for Research on Cancer; 1998. Available at: http://monographs.iarc.fr/ENG/Monographs/suppl7/suppl7.pdf
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