Occupational Exposures and Laryngeal Cancer among Non-smoking and Non-drinking Men

Abstract

In a previous hospital-based case-control study, we found an association between laryngeal cancer and exposure to occupational silica, cotton dust, diesel exhaust, gasoline exhaust, and polycyclic aromatic hydrocarbons (PAH). We evaluated the data further to investigate risks from occupational exposure among non-smoking and non-alcohol drinking (NSND) men. We analyzed 189 male NSND primary laryngeal cancer cases and 536 NSND controls. Case group included 86 supraglottic (45.5%), 47 glottic (24.9%), and 56 subglottic and non-classified tumors (29.6%). Age-adjusted odds ratios (OR) and 95% confidence intervals (95%CI) were calculated for occupational exposure. The most prevalent exposures among cases were PAH (40.7%), diesel exhaust (29.1%), and solvents (24.9%). An excess of laryngeal cancer occurred with silica (OR, 1.7; 95%CI, 1.1–13.0) and PAH (OR, 1.5; 95%CI, 1.1–2.2). An observed excess risk from silica and PAH exposure among NSND laryngeal cancer cases supports the suggested link between occupational exposure and laryngeal cancer.     

A Case–Control Study of Lung Cancer Nested in a Cohort of European Asphalt Workers

Background

We conducted a nested case–control study in a cohort of European asphalt workers in which an increase in lung cancer risk has been reported among workers exposed to airborne bitumen fume, although potential bias and confounding were not fully addressed.

Objective

We investigated the contribution of exposure to bitumen, other occupational agents, and tobacco smoking to the risk of lung cancer among asphalt workers.

Methods

Cases were cohort members in Denmark, Finland, France, Germany, the Netherlands, Norway, and Israel who had died of lung cancer between 1980 and the end of follow-up (2002–2005). Controls were individually matched in a 3:1 ratio to cases on year of birth and country. We derived exposure estimates for bitumen fume and condensate, organic vapor, and polycyclic aromatic hydrocarbons, as well as for asbestos, crystalline silica, diesel motor exhaust, and coal tar. Odds ratios (ORs) were calculated for ever-exposure, duration, average exposure, and cumulative exposure after adjusting for tobacco smoking and exposure to coal tar.

Results

A total of 433 cases and 1,253 controls were included in the analysis. The OR was 1.12 [95% confidence interval (CI), 0.84–1.49] for inhalation exposure to bitumen fume and 1.17 (95% CI, 0.88–1.56) for dermal exposure to bitumen condensate. No significant trend was observed between lung cancer risk and duration, average exposure, or cumulative exposure to bitumen fume or condensate.

Conclusions

We found no consistent evidence of an association between indicators of either inhalation or dermal exposure to bitumen and lung cancer risk. A sizable proportion of the excess mortality from lung cancer relative to the general population observed in the earlier cohort phase is likely attributable to high tobacco consumption and possibly to coal tar exposure, whereas other occupational agents do not appear to play an important role.     

Application of two job indices for general occupational demands in a pooled analysis of case–control studies on lung cancer

Objectives:We investigated general job demands as a risk factor for lung cancer as well as their role in the association between occupational prestige and lung cancer.Methods:In 13 case–control studies on lung cancer, as part of the international SYNERGY project, we applied indices for physical (PHI) and psychosocial (PSI) job demands – each with four categories (high to low). We estimated odds ratios (OR) and 95% confidence intervals (CI) for lung cancer by unconditional logistic regression, separately for men and women and adjusted for study centre, age, smoking behavior, and former employment in occupations with potential exposure to carcinogens. Further, we investigated, whether higher risks among men with low occupational prestige (Treiman’s Standard International Occupational Prestige Scale) were affected by adjustment for the job indices.Results:In 30 355 men and 7371 women, we found increased risks (OR) for lung cancer with high relative to low job demands in both men [PHI 1.74 (95% CI 1.56–1.93), PSI 1.33 (95% CI 1.17–1.51)] and women [PHI 1.62 (95% CI 1.24–2.11), PSI 1.31 (95% CI 1.09–1.56)]. OR for lung cancer among men with low occupational prestige were slightly reduced when adjusting for PHI [low versus high prestige OR from 1.44 (95% CI 1.32–1.58) to 1.30 (95% CI 1.17–1.45)], but not PSI.Conclusions:Higher physical job demands were associated with increased risks of lung cancer, while associations for higher psychosocial demands were less strong. In contrast to physical demands, psychosocial demands did not contribute to clarify the association of occupational prestige and lung cancer.     

Risk of premenopausal breast cancer in association with occupational exposure to polycyclic aromatic hydrocarbons and benzene.

OBJECTIVES: This study examined the relationship between risk of premenopausal breast cancer and occupational exposure to benzene and polycyclic aromatic hydrocarbons (PAH) and whether the proposed relationship between PAH and breast cancer differed by tumor estrogen receptor (ER) status. METHODS: In a case-referent study of premenopausal breast cancer, occupational histories and other information were obtained through interviews, and job-exposure matrices were used to assess exposure to PAH and benzene. RESULTS: A dose-response relationship for the probability of exposure to benzene [low: odds ratio (OR) 1.64, 95% confidence interval (95% CI) 0.64-4.21; high: OR 1.95, 95% CI 1.14-3.33) and to PAH (low: OR 1.56, 95% CI 0.78-3.12; high: OR 2.40, 95% CI 0.96-6.01). Risk increased with duration of exposure to benzene, but not to PAH. A dose-response relationship was not evident for the intensity of exposure to benzene or to PAH. When analyses were stratified by tumor ER status, PAH exposure was related to a greater increase in the risk of ER-positive (OR 2.27, 95% CI 1.14-4.54) than ER-negative (OR 1.12, 95% CI 0.47-2.64) breast cancer. Risk of ER-positive, but not ER-negative, tumors increased with the probability of exposure to PAH. CONCLUSIONS: The findings suggest an association between risk and occupational exposure to benzene. Although it was difficult to study PAH independently of benzene, there was some suggestion of an association between PAH exposure and ER-positive tumors. These data should be interpreted with caution because of the limitations of this study, including low-response rates and small numbers of exposed persons.     

Exposure to Dichlorodiphenyltrichloroethane and the Risk of Breast Cancer: A Systematic Review and Meta-analysis

Objectives

This study extended and updated a meta-analysis of the association between exposure to dichlorodiphenyltrichloroethane (DDT) and the risk of breast cancer.

Methods

We reviewed the published literature on exposure to DDE and breast cancer risk to update a meta-analysis from 2004. The total of 35 studies included 16 hospital-based case–control studies, 11 population-based case–control studies, and 10 nested case–control studies identified through keyword searches in the PubMed and EMBASE databases.

Results

The summary odds ratio (OR) for the identified studies was 1.03 (95% confidence interval 0.95–1.12) and the overall heterogeneity in the OR was observed (I² = 40.9; p = 0.006). Subgroup meta-analyses indicated no significant association between exposure to DDE and breast cancer risk by the type of design, study years, biological specimen, and geographical region of the study, except from population-based case–control studies with estimated DDE levels in serum published in 1990s.

Conclusion

Existing studies do not support the view that DDE increases the risk of breast cancer in humans. However, further studies incorporating more detailed information on DDT exposure and other potential risk factors for breast cancer are needed.     

Occupational exposure to noise in relation to pregnancy-related hypertensive disorders and diabetes

Objectives:Exposure to environmental noise has been associated with an increased risk of cardiovascular diseases and diabetes, but evidence for occupational noise is limited and conflicting, especially related to pregnancy outcomes. This study aimed to evaluate the association of occupational noise exposure with hypertensive disorders of pregnancy (HDP) and gestational diabetes.Methods:Our population-based cohort study utilized data on 1 109 516 singletons born to working mothers in Sweden between 1994–2014 from the Medical Birth Register and the Longitudinal Integration Database for Health Insurance and Labor Market Studies. Noise exposure came from a job exposure matrix (JEM) in five categories <70, 70–74, 75–80, 80–85, >85 dB(A). Relative risks (RR), adjusted for confounders and other job exposures, were calculated by modified Poisson regressions for the full sample and a subsample of first-time mothers reporting full-time work.Results:Exposure to 80–85 dB(A) of noise was associated with an increased risk of all HDP [RR 1.12, 95% confidence interval (CI) 1.05–1.18] and preeclampsia alone (RR 1.14, 95% CI 1.07–1.22) in the full sample. Results were similar for first-pregnancy, full-time workers. Exposure to >85 dB(A) of noise was also associated with an increased risk of gestational diabetes (RR 1.57, 95% CI 1.10–2.24) in the analysis restricted to first-time mothers working full-time.Conclusion:In this study, exposure to noise was associated with an increased risk for HDP and gestational diabetes, particularly in first-time mothers who work full-time. Further research is needed to confirm findings and identify the role of hearing protection on this association so prevention policies can be implemented.     

Occupational exposures to extremely low frequency magnetic fields and postmenopausal breast cancer

BACKGROUND: The association between occupational exposure to extremely low frequency magnetic fields (ELF-MF) and risk of postmenopausal breast cancer was assessed in a case-control study. METHODS: Breast cancer cases were compared to cancer controls. Interviewers elicited information on risk factors and on lifetime work history. Industrial hygienists assigned to each job average duration of exposure to ELF-MF at four levels of intensities ("none," <0.2 microT; "low," 0.2-<0.5microT; "medium," 0.5-<1microT; "high," > or =1-10microT). Unconditional logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: A total number of 608 cases and 667 controls participated. Adjusting for accepted breast cancer risk factors, we found an OR of 1.13 for lifetime occupational exposure to ELF-MF at medium or high intensities. Risks were larger for exposures before age 35 (OR = 1.40), and statistically significant for exposures before 35 among cases with progesterone receptor positive tumors (OR = 1.56, 95% CI=1.02-2.39). CONCLUSIONS: There appears to be a small increased risk for breast cancer among postmenopausal women exposed occupationally to ELF-MF.     

Laryngeal and hypopharyngeal cancers and occupational exposure to formaldehyde and various dusts: a case-control study in France

OBJECTIVES—A case-control study was conducted in France to assess possible associations between occupational exposures and squamous cell carcinomas of the larynx and hypopharynx.
METHODS—The study was restricted to men, and included 201 hypopharyngeal cancers, 296 laryngeal cancers, and 296 controls (patients with other tumour sites). Detailed information on smoking, alcohol consumption, and lifetime occupational history was collected. Occupational exposure to seven substances (formaldehyde, leather dust, wood dust, flour dust, coal dust, silica dust, and textile dust) was assessed with a job exposure matrix. Exposure variables used in the analysis were probability, duration, and cumulative level of exposure. Odds ratios (ORs) with their 95% confidence intervals (95% CIs) were estimated by unconditional logistic regression, and were adjusted for major confounding factors (age, smoking, alcohol, and when relevant other occupational exposures).
RESULTS—Hypopharyngeal cancer was found to be associated with exposure to coal dust (OR 2.31, 95% CI 1.21 to 4.40), with a significant rise in risk with probability (p<0.005 for trend) and level (p<0.007 for trend) of exposure. Exposure to coal dust was also associated with an increased risk of laryngeal cancer (OR 1.67, 95% CI 0.92 to 3.02), but no dose-response pattern was found. A significant relation, limited to hypopharyngeal cancer, was found with the probability of exposure to formaldehyde (p<0.005 for trend), with a fourfold risk for the highest category (OR 3.78 , 95% CI 1.50 to 9.49). When subjects exposed to formaldehyde with a low probability were excluded, the risk also increased with duration (p<0.04) and cumulative level of exposure (p<0.14). No significant association was found for any other substance.
CONCLUSION—These results indicate that exposure to formaldehyde and coal dust may increase the risk of hypopharyngeal cancer.


Keywords: laryngeal cancer; hypopharyngeal cancer; occupational exposure; job exposure matrix; formaldehyde; coal dust     

Lung cancer and vehicle exhaust in trucking industry workers

Background

An elevated risk of lung cancer in truck drivers has been attributed to diesel exhaust exposure. Interpretation of these studies specifically implicating diesel exhaust as a carcinogen has been limited because of limited exposure measurements and lack of work records relating job title to exposure-related job duties.

Objectives

We established a large retrospective cohort of trucking company workers to assess the association of lung cancer mortality and measures of vehicle exhaust exposure.

Methods

Work records were obtained for 31,135 male workers employed in the unionized U.S. trucking industry in 1985. We assessed lung cancer mortality through 2000 using the National Death Index, and we used an industrial hygiene review and current exposure measurements to identify jobs associated with current and historical use of diesel-, gas-, and propane-powered vehicles. We indirectly adjusted for cigarette smoking based on an industry survey.

Results

Adjusting for age and a healthy-worker survivor effect, lung cancer hazard ratios were elevated in workers with jobs associated with regular exposure to vehicle exhaust. Mortality risk increased linearly with years of employment and was similar across job categories despite different current and historical patterns of exhaust-related particulate matter from diesel trucks, city and highway traffic, and loading dock operations. Smoking behavior did not explain variations in lung cancer risk.

Conclusions

Trucking industry workers who have had regular exposure to vehicle exhaust from diesel and other types of vehicles on highways, city streets, and loading docks have an elevated risk of lung cancer with increasing years of work.     

Night and shift work and incidence of cerebrovascular disease – a prospective cohort study of healthcare employees in Stockholm

ObjectiveThis study aimed to investigate the effects of various aspects of night and shift work regarding incident cerebrovascular disease (CeVD).MethodsThe cohort included 26 667 women and 3793 men (nurses and nursing assistants) who were employed for at least one year 2008–2016 in Region Stockholm, Sweden. Information about the cohort and working hours were obtained from a computerized employee-register and diagnoses were retrieved from national and regional registers. We used discrete time proportional hazard models to assess the risk of CeVD (2009–2017), in relation to work hour characteristics, adjusting for sex, age, country of birth, education and profession.ResultsWe observed an excess risk of CeVD (N=223) among employees who, during the preceding year, worked night shifts >30 times [hazard ratio (HR) 1.44, 95% confidence interval (CI) 1.04–1.99] or ≥3 consecutive night shifts >15 times (HR 1.69, 95% CI 1.18–2.42) or with >30 quick returns (<28 hours) from night shifts (HR 1.52, 95% CI 1.10–2.10) compared to those who did not work nights. We also observed an excess risk among employees with a long duration (>5 years) of exposure to night shift work (HR 1.87, 95% CI 1.27–2.77), all supported by a dose–response pattern.ConclusionsOur results show that the risk of CeVD among nurses and nursing assistants is associated with night shift work. The number of years with night shift work, the frequency of night shifts per year, the frequency of consecutive night shifts, and short recovery after night shifts influenced the risk. Work schedules aiming at minimizing these aspects of night shift work may reduce the risk.     

Noticing pesticide spray drift from agricultural pesticide application areas and breast cancer: a case‐control study

Objectives : To examine the relationship between self‐reported noticing of pesticide spray drift from agricultural areas and breast cancer. Methods : A case‐control study of breast cancer was conducted in Western Australia from 2009 to 2011. Awareness of pesticide spray drift from agricultural areas was assessed by a self‐report of whether the participant had noticed spray drift. To evaluate recall bias, we stratified the analysis by participants' belief about whether pesticides increase the risk of breast cancer. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). This analysis included 1,743 controls and 1,169 cases. Sensitivity analysis for potential selection and misclassification bias was also conducted. Results : Among women who reported ‘ever noticed’ pesticide spray drift from agricultural areas, an increased risk of breast cancer was also observed (OR=1.43; 95% CI 1.15, 1.78). A dose response relationship between lifetime exposure to noticing pesticide spray drift and risk of breast cancer was observed (p<0.001). An increased risk of breast cancer was observed among women who noticed pesticide spray drift: initially at the age of 20 or younger (OR=1.61; 95% CI 1.19, 2.16); at least 20 years before diagnosis (OR=1.51; 95% CI 1.19, 1.92); and for 10 years or more (OR=1.51; 95% CI 1.18, 1.94). Conclusion : These findings support the hypothesis that women who ever noticed spray drift or who first noticed spray drift at a younger age had increased risk of breast cancer.     

Case-control study on occupational exposure to diesel exhaust and lung cancer risk.

The association between lung cancer and occupations with probable exposure to diesel exhaust (DE) was studied among 2,584 cases and 5,099 hospital controls. The crude odds ratio (OR) for probable exposure was 1.31 (95% confidence interval [CI] 1.09-1.57), but adjustment for smoking and other confounders reduced the estimate to 0.95 (95% CI = 0.78-1.16). Similar results were observed for truck drivers, the only occupational category large enough for separate analysis. Data on self-reported exposure for 477 cases and 946 controls revealed a crude OR of 1.45 (95% CI = 0.93-2.27), which was reduced to 1.21 (95% CI = 0.78-2.02) after controlling for smoking and other confounders. The present results and a review of the literature do not definitively support an etiologic association between DE exposure and elevated lung cancer risk.     

A Systematic Review and Meta-analysis of Childhood Leukemia and Parental Occupational Pesticide Exposure

Objectives

We conducted a systematic review and meta-analysis of childhood leukemia and parental occupational pesticide exposure.

Data sources

Searches of MEDLINE (1950–2009) and other electronic databases yielded 31 included studies.

Data extraction

Two authors independently abstracted data and assessed the quality of each study.

Data synthesis

Random effects models were used to obtain summary odds ratios (ORs) and 95% confidence intervals (CIs). There was no overall association between childhood leukemia and any paternal occupational pesticide exposure (OR = 1.09; 95% CI, 0.88–1.34); there were slightly elevated risks in subgroups of studies with low total-quality scores (OR = 1.39; 95% CI, 0.99–1.95), ill-defined exposure time windows (OR = 1.36; 95% CI, 1.00–1.85), and exposure information collected after offspring leukemia diagnosis (OR = 1.34; 95% CI, 1.05–1.70). Childhood leukemia was associated with prenatal maternal occupational pesticide exposure (OR = 2.09; 95% CI, 1.51–2.88); this association was slightly stronger for studies with high exposure-measurement-quality scores (OR = 2.45; 95% CI, 1.68–3.58), higher confounder control scores (OR = 2.38; 95% CI, 1.56–3.62), and farm-related exposures (OR = 2.44; 95% CI, 1.53–3.89). Childhood leukemia risk was also elevated for prenatal maternal occupational exposure to insecticides (OR = 2.72; 95% CI, 1.47–5.04) and herbicides (OR = 3.62; 95% CI, 1.28–10.3).

Conclusions

Childhood leukemia was associated with prenatal maternal occupational pesticide exposure in analyses of all studies combined and in several subgroups. Associations with paternal occupational pesticide exposure were weaker and less consistent. Research needs include improved pesticide exposure indices, continued follow-up of existing cohorts, genetic susceptibility assessment, and basic research on childhood leukemia initiation and progression.     

Household and occupational exposure to pesticides and risk of breast cancer

The association between breast cancer in women and the use of household or occupational pesticides was examined in a population-based case-control study. This study was conducted in Western Australia in 2009–2011and included 1,789 controls and 1,205 cases. Information on household pesticide exposure was collected from questionnaires. For occupational pesticide exposure, job-specific modules (JSMs) were used. To evaluate potential recall bias, we stratified the analysis by belief about whether pesticides contribute to breast cancer. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Women’s exposures to pesticides in households and workplaces were not related to increased risk of breast cancer (OR?=?1.10; CI: 0.86–1.37) and (OR?=?0.77; CI: 0.45–1.32), respectively. The prevalence of occupational exposure to pesticides among women in our study was low. In the stratified analyses, the odd ratios associated with household pesticide use were similar among participants who believed pesticides increased breast cancer risk and those who did not. The results of our study did not show associations between breast cancer and household or occupational exposure to pesticides.     

Metalworking fluids and cancer mortality in a US autoworker cohort (1941–2015)

Objectives:This report describes the extended follow-up (1941–2015) of a cohort of 38 549 automobile manufacturing workers with potential exposure to metalworking fluids (MWF). The outcomes of interest were mortality from cancers of the esophagus, stomach, intestine, rectum, bladder, liver, pancreas, larynx, lung, skin, prostate, brain, and female breast, as well as leukemia. This report includes 5472 deaths from cancer, more than ten times the numbers of deaths in our last summary report published 20 years ago.Methods:Standardized mortality ratios were computed for the entire study period. Adjusted hazard ratios (HR) were estimated in Cox proportional hazard models with categorical variables for cumulative exposure to each type of MWF.Results:Exposure–response patterns are consistent with prior mortality reports from this cohort. We found increased risk of skin and female breast cancer with straight fluids. For the first time, we found elevated risk of stomach cancer mortality. Overall, many of the exposure–response results did not suggest an association with MWF.Conclusions:Mortality is a poor proxy for cancer diagnosis for treatable cancers and not the optimal outcome measure in etiological studies. Although the HR presented here handle bias from the healthy worker hire effect and left truncation, they do not handle bias from healthy worker survivor effect, which likely results in underestimates of the health impacts of MWF. Although this updated summary provides some information on the risk of cancer from MWF, targeted future analyses will help clarify associations.     

Vehicular Traffic–Related Polycyclic Aromatic Hydrocarbon Exposure and Breast Cancer Incidence: The Long Island Breast Cancer Study Project (LIBCSP)

Background

Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental pollutants, known human lung carcinogens, and potent mammary carcinogens in laboratory animals. However, the association between PAHs and breast cancer in women is unclear. Vehicular traffic is a major ambient source of PAH exposure.

Objectives

Our study aim was to evaluate the association between residential exposure to vehicular traffic and breast cancer incidence.

Methods

Residential histories of 1,508 participants with breast cancer (case participants) and 1,556 particpants with no breast cancer (control participants) were assessed in a population-based investigation conducted in 1996–1997. Traffic exposure estimates of benzo[a]pyrene (B[a]P), as a proxy for traffic-related PAHs, for the years 1960–1995 were reconstructed using a model previously shown to generate estimates consistent with measured soil PAHs, PAH–DNA adducts, and CO readings. Associations between vehicular traffic exposure estimates and breast cancer incidence were evaluated using unconditional logistic regression.

Results

The odds ratio (95% CI) was modestly elevated by 1.44 (0.78, 2.68) for the association between breast cancer and long-term 1960–1990 vehicular traffic estimates in the top 5%, compared with below the median. The association with recent 1995 traffic exposure was elevated by 1.14 (0.80, 1.64) for the top 5%, compared with below the median, which was stronger among women with low fruit/vegetable intake [1.46 (0.89, 2.40)], but not among those with high fruit/vegetable intake [0.92 (0.53, 1.60)]. Among the subset of women with information regarding traffic exposure and tumor hormone receptor subtype, the traffic–breast cancer association was higher for those with estrogen/progesterone-negative tumors [1.67 (0.91, 3.05) relative to control participants], but lower among all other tumor subtypes [0.80 (0.50, 1.27) compared with control participants].

Conclusions

In our population-based study, we observed positive associations between vehicular traffic-related B[a]P exposure and breast cancer incidence among women with comparatively high long-term traffic B[a]P exposures, although effect estimates were imprecise.

Citation

Mordukhovich I, Beyea J, Herring AH, Hatch M, Stellman SD, Teitelbaum SL, Richardson DB, Millikan RC, Engel LS, Shantakumar S, Steck SE, Neugut AI, Rossner P Jr., Santella RM, Gammon MD. 2016. Vehicular traffic–related polycyclic aromatic hydrocarbon exposure and breast cancer incidence: the Long Island Breast Cancer Study Project (LIBCSP). Environ Health Perspect 124:30–38; http://dx.doi.org/10.1289/ehp.1307736     

Diesel exhaust exposure and bladder cancer risk

A total of 136 cases of men with urinary bladder cancer and 272 matched hospital controls were examined for potential exposure to diesel exhaust. A lifetime occupational history was obtained for all subjects in the study and assessment of exposure to diesel exhaust was based on the job titles of the subject and self-reported exposure. The risk was assessed by odds ratios, with adjustment for confounding variables, in particular cigarette smoking. There was no evidence of elevated risk in occupations with possible or probable exposure (the ORs adjusted for smoking were 1.1. and 0.9 respectively). Truck driving alone was also not associated with elevated risk (adjusted OR=0.5). There was a weak positive crude association with any exposure, including self-reports (OR=1.4); however after adjustment for smoking, the estimate did not retain statistical significance (OR=1.2, 95% CI=0.8-2.0). This study provides little to support the hypothesis of an excess of bladder cancer risk from occupational exposure to diesel exhaust.Corresponding author.     

Genetic Variation Interacts with Selenium Exposure Regarding Breast Cancer Risk: Assessing Dietary Intake,Serum Levels and Genetically Elevated Selenium Levels

Selenium has been suggested to be protective regarding breast cancer risk but no overall effect has been established. Genetics may modify the effect. This study compares the effect of selenium exposure on breast cancer risk between women with different alleles in single-nucleotide polymorphisms (SNPs). The Malmö Cancer and Diet Study, a cohort including 17,035 women and >25 years of follow-up on breast cancer diagnosis, was used. Five promising SNPs regarding interaction with selenium exposure were selected from the literature: rs1050450, rs4880, rs3877899, rs7579, and rs71304. Selenium exposure was assessed in three ways: genetically elevated (n = 16,429), dietary intake (n = 15,891) and serum levels (n = 2037) at baseline. Cox regression and logistic regression analyses evaluated breast cancer risk from selenium exposure, stratified for the SNPs and adjusted for risk factors. A total of 1946 women were diagnosed with breast cancer. Women with T/T alleles in rs1050450 had lower breast cancer risk compared with C/C, HR 0.81 (0.68–0.96). Interaction by rs1050450 limited a protective effect of higher selenium intake to T/T carriers, HR 0.68 (0.43–1.08) for intermediate intake and HR 0.63 (0.40–1.00) for high intake. No interactions or risk differences were seen for other SNPs or for serum selenium or genetically elevated selenium. The results indicate that genetic variation in rs1050450 might affect breast cancer risk and that selenium exposure could be a possible modifiable risk factor for breast cancer among women with that variation.