Objective: To determine whether exposures in the workplace to organic solvents and to other agents, such as polycyclic aromatic hydrocarbons, are associated with increased risks of developing postmenopausal breast cancer.Methods: Between 1996 and 1997 a case–control study was conducted in Montreal, Quebec. Cases comprised 556 women, aged 50–75 years, with incident malignant breast cancer, and their controls were 613 women with other cancers, frequency matched for age, date of diagnosis and hospital. An expert team of chemists and industrial hygienists translated their job histories into exposure to about 300 agents.Results: Odds ratios (ORs) were increased for the usual risk factors for breast cancer and, adjusting for these, risks increased with occupational exposure to several agents, and were highest for exposures occurring before age 36 years. Increased ORs were found for each 10-year increment in duration of exposure, before age 36 years (OR_<36), to acrylic fibres (OR_<36=7.69) and to nylon fibres (OR_<36=1.99). For oestrogen-positive and progesterone-negative tumours, the OR doubled or more for each 10-year increase in exposure to monoaromatic hydrocarbons, and to acrylic and rayon fibres. The OR_<36also doubled for exposure to organic solvents that metabolise into reactive oxygen species, and to acrylic fibres. A threefold increase was found for oestrogen- and progesterone-positive tumours, with exposure to polycyclic aromatic hydrocarbons from petroleum sources.Conclusion: Certain occupational exposures appear to increase the risk of developing postmenopausal breast cancer, although some findings might be due to chance or to undetected bias. Our findings are consistent with the hypothesis that breast tissue is more sensitive to adverse effects if exposure occurs when breast cells are still proliferating. More refined analyses, adjusting for hormonal receptor subtypes and studies focusing on certain chemical exposures are required to further our understanding of the role of chemicals in the development of breast cancer.

Public concern about the impact of endocrine disrupting chemicals (EDCs) on both humans and the environment is growing steadily. Epidemiologic research provides key information towards our understanding of the relationship between environmental exposures like EDCs and human health outcomes. Intended for researchers in disciplines complementary to epidemiology, this paper highlights the importance and challenges of epidemiologic research in order to present the key elements pertaining to the design and interpretation of an epidemiologic study on EDCs. The conduct of observational studies on EDCs derives from a thoughtful research question, which will help determine the subsequent methodological choices surrounding the careful selection of the study population (including the comparison group), the adequate ascertainment of exposure(s) and outcome(s) of interest, and the application of methodological and statistical concepts more specific to epidemiology. The interpretation of epidemiologic results may be arduous due to the latency occurring between EDC exposure and certain outcome(s), the complexity in capturing EDC exposure(s), and traditional methodological and statistical issues that also deserve consideration (e.g., confounding, effect modification, non-monotonic responses). Moving forward, we strongly advocate for an integrative approach of expertise in the fields of epidemiology, exposure science, risk assessment and toxicology to adequately study the health risks associated with EDCs while tackling their challenges.

This review examines epidemiological evidence relating to cancers in the primary aluminum industry where most of what is known relates to Söderberg operations or to mixed Söderberg/prebake operations. Increased lung and bladder cancer risks have been reported in Söderberg workers from several countries, but not in all. After adjustment for smoking, these cancer risks still increase with cumulative exposure to benzo(a)pyrene, used as an index of coal tar pitch volatiles exposure. Limited evidence has been gathered in several cohorts for an increased risk of tumors at other sites, including stomach, pancreas, rectum/rectosigmoid junction, larynx, buccal cavity/pharynx, kidney, brain/nervous system, prostate, and lymphatic/hematopoietic tissues (in particular non-Hodgkin lymphoma, Hodgkin disease, and leukemia). Nevertheless, for most of these tumor sites, the relationship with specific exposures has not been demonstrated clearly and further follow-up of workers is warranted.

Introduction: We have previously shown that a tag single nucleotide polymorphism (rs10235235), which maps to the CYP3A locus (7q22.1), was associated with a reduction in premenopausal urinary estrone glucuronide levels and a modest reduction in risk of breast cancer in women age ≤50 years. Methods: We further investigated the association of rs10235235 with breast cancer risk in a large case control study of 47,346 cases and 47,570 controls from 52 studies participating in the Breast Cancer Association Consortium. Genotyping of rs10235235 was conducted using a custom Illumina Infinium array. Stratified analyses were conducted to determine whether this association was modified by age at diagnosis, ethnicity, age at menarche or tumor characteristics. Results: We confirmed the association of rs10235235 with breast cancer risk for women of European ancestry but found no evidence that this association differed with age at diagnosis. Heterozygote and homozygote odds ratios (ORs) were OR = 0.98 (95% CI 0.94, 1.01; P = 0.2) and OR = 0.80 (95% CI 0.69, 0.93; P = 0.004), respectively (P_trend = 0.02). There was no evidence of effect modification by tumor characteristics. rs10235235 was, however, associated with age at menarche in controls (P_trend = 0.005) but not cases (P_trend = 0.97). Consequently the association between rs10235235 and breast cancer risk differed according to age at menarche (P_het = 0.02); the rare allele of rs10235235 was associated with a reduction in breast cancer risk for women who had their menarche age ≥15 years (OR_het = 0.84, 95% CI 0.75, 0.94; OR_hom = 0.81, 95% CI 0.51, 1.30; P_trend = 0.002) but not for those who had their menarche age ≤11 years (OR_het = 1.06, 95% CI 0.95, 1.19, OR_hom = 1.07, 95% CI 0.67, 1.72; P_trend = 0.29). Conclusions: To our knowledge rs10235235 is the first single nucleotide polymorphism to be associated with both breast cancer risk and age at menarche consistent with the well-documented association between later age at menarche and a reduction in breast cancer risk. These associations are likely mediated via an effect on circulating hormone levels.