BACKGROUND:Epidemiologic evidence demonstrates increased lung, bladder, and skin cancer risk among individuals exposed to arsenic in drinking water. Some studies report associations with prostate cancer, but data are limited. This study aimed to examine the association between arsenic in drinking water and prostate cancer in Northern Chile. With its wide range of exposure (<10-860 µg/L), large population, and accurate information on historic exposures, Northern Chile is the best place to investigate the human carcinogenic effects of arsenic. METHODS:A case-control study conducted from 2015 to 2019 enrolled 343 prostate cancer cases and 337 age-matched controls among men ages ≥40 years. Cases were ascertained from cancer committees, hospitals, and medical facilities in the area. Controls were ascertained from the Chile Voter Registry, including >90% of adults ages >50 years. Information on lifetime arsenic exposure and potential confounders such as smoking, family history, and prostate cancer screening were collected. RESULTS:Twenty-three percent of participants were exposed to arsenic concentrations >800 µg/L in their lifetime (80× recommended thresholds). Cases and controls were demographically similar. After adjustment for age and smoking status, participants with the highest quartile of lifetime cumulative and average arsenic concentrations in drinking water each had 1.14 (95% confidence interval, 0.71-1.84) and 1.17 (95% confidence interval, 0.73-1.89) times the odds of prostate cancer compared with participants with the lowest quartile of exposure, respectively. CONCLUSIONS:Arsenic exposure in drinking water, even at high levels, was not associated with increased risk of prostate cancer. IMPACT:Our findings suggest that arsenic is not a risk factor for prostate cancer.

PDF - 115K, Table S1. Comparison of subjects included in this analysis to subjects excluded because they had high exposures both in early life and adulthood. Table S2. Comparison of residences of the Chile case control study controls at the time of ascertainment to the 2002 Chile census. Table S3. Cancer odds ratios in subjects exposed in utero and childhood using different age categories to define early-life exposure.

Background: We previously reported chronic respiratory effects in children who were then 7–17 years of age in Matlab, Bangladesh. One group of children had been exposed to high concentrations of arsenic in drinking water in utero and early childhood (average 436 µg/L), and the other group of children were never known to have been exposed to >10 µg/L. The exposed children, both males and females, had marked increases in chronic respiratory symptoms. Methods: The current study involves a further follow-up of these children now 14–26 years of age with 463 located and agreeing to participate. They were interviewed for respiratory symptoms and lung function was measured. Data were collected on smoking, body mass index (BMI), and number of rooms in the house as a measure of socioeconomic status. Results: Respiratory effects were still present in males but not females. In the high exposure group (>400 µg/L in early life) the odds ratio (OR) among male participants for dry cough in the last 12 months was 2.36 (95% confidence interval [CI] = 1.21, 4.63, P = 0.006) and for asthma OR = 2.51 (95% CI = 1.19, 5.29, P = 0.008). Forced vital capacity (FVC) was reduced in males in the early life high-exposure group compared with those never exposed (−95ml, P = 0.04), but not in female participants. Conclusions: By the age range 14–26, there was little remaining evidence of chronic respiratory effects in females but pronounced effects persisted in males. Mechanisms for the marked male female differences warrant further investigation along with further follow-up to see if respiratory effects continue in males.

OBJECTIVE:Evaluate whether arsenic-related diabetes risks differ between people of low and high socioeconomic status (SES). METHODS:We used data collected between October 2007-December 2010 from a population-based cancer case-control study (N = 1301) in Northern Chile, an area with high arsenic water concentrations (>800 µg/L) and comprehensive records of past exposure. Information on lifetime exposure and potential confounders were obtained using structured interviews, questionnaires, and residential histories. Type 2 diabetes was defined as physician-diagnosed diabetes or oral hypoglycemic medication use. SES was measured using a 14-point scale based on ownership of household appliances, cars, internet access, or use of domestic help. Logistic regression was used to assess the relationship between arsenic and diabetes within strata of SES. RESULTS:Among those with low SES, the odds ratio (OR) for diabetes comparing individuals in the highest to lowest tertile of lifetime average arsenic exposure was 2.12 (95% confidence interval (CI) 1.29-3.49, p = 0.004). However, those in the high SES group were not at increased risk (OR = 1.12 [95% CI = 0.72-1.73]). CONCLUSIONS:Our findings provide evidence that risks of arsenic-related diabetes may be higher in Chile in people with low versus high SES.

Background/Aim: Evidence suggests that exposure to arsenic through drinking water increases the risk of non-malignant respiratory illnesses including impairment of lung function in adults. However, early life arsenic exposure and subsequent respiratory system effects in adolescents have not been reported so far. Methods: The study was conducted in rural Bangladesh, Matlab. A cohort of 200 children now aged 11-22 years were enrolled of which 107 had in utero and early childhood (first five years) exposure to drinking water arsenic concentration over 400µg/L (exposed group) and 93 had less than 10 µg/L (unexposed group). Histories of respiratory symptoms were collected through a validated structured questionnaire (ISAAC). Lung function (FEV1, FVC) was tested by EasyOne spirometry following the standard American Thoracic Society criteria. Water arsenic concentrations were measured by hydride generation atomic absorption spectrophotometry. Results: The mean age was 15 years. Chronic respiratory symptoms were evident in male participants in the exposed group. In an adjusted model, boys with in early life arsenic exposure (>400 µg/L) were more likely to report wheezing attacks 1-3 times/week (Prevalence Odds Ratio (POR): 4.99, 95% Confidence Interval (CI): 1.00-24.9), wheezing after exercise (POR: 4.14, 95% CI: 1.05-16.4) and waking up with chest tightness (POR: 5.01, 95% CI: 1.00-25.0). Decrease in FEV1 (-117.3 ml, CI: -246.5, 11.8) and FVC (-135.2 ml, CI: -269.9, -0.37) were observed in male respondents in the exposed group compared to the unexposed. No respiratory impairment was observed among exposed girls. Conclusions: High exposure to arsenic in utero and early childhood may result in increased risk of chronic respiratory symptoms and decrements in lung function in adolescent males. We plan to follow this unique cohort further to see if early life arsenic exposure respiratory effects persist in males as they grow older, and remain absent in females.

Arsenic in drinking water is known to cause cancer and noncancer diseases, but little is known about its association with age at exposure. Here, we investigated age at arsenic exposure and mortality in Antofagasta, Chile, 30-40 years after a distinct period of very high water arsenic concentrations (1958-1970). We calculated standardized mortality ratios (SMRs) comparing Antofagasta with the rest of Chile for 2001-2010 by sex and age at potential first exposure. A remarkable relationship with age at first exposure was found for bronchiectasis, with increased risk in adults 30-40 years after exposure being confined to those who were in utero (SMR = 11.7, 95% confidence interval (CI): 4.3, 25.4) or aged 1-10 years (SMR = 5.4, 95% CI: 1.1, 15.8) during the high-exposure period. Increased SMRs for lung, bladder, and laryngeal cancer were evident for exposures starting at all ages, but the highest SMRs were for exposures beginning at birth (for bladder cancer, SMR = 16.0 (95% CI: 10.3, 23.8); for laryngeal cancer, SMR = 6.8 (95% CI: 2.2, 15.8); for lung cancer, SMR = 3.8 (95% CI: 2.9, 4.9)). These findings suggest that interventions targeting early-life arsenic exposure could have major impacts in reducing long-term mortality due to arsenic 30-40 years after exposure ends.

Background: Evidence suggests that prolonged exposure to arsenic through drinking water increases the risk of hypertension in adults. However, few studies have evaluated the impact of early life arsenic exposure on blood pressure in adolescents and young adults. This study aimed to assess the association between in-utero-and-childhood arsenic exposure and prehypertension among the participants aged 11 to 22 years.Methods: The study was conducted in rural Bangladesh, Matlab. A cohort of 200 adolescents and young adults were enrolled of which 107 had in utero and first five years exposure to water arsenic concentration over 400µg/L (exposed group) and 93 had less than 10 µg/L(unexposed group). Blood pressure was measured using a standard mercury sphygmomanometer with an appropriately sized cuff. Prehypertension in adolescents was defined as systolic blood pressure (SBP) and/or diastolic blood pressure (DBP) between the 90th and 95th percentile for age, sex and height. For the subjects 18 years and above, prehypertension was defined as SBP ranging from 120-139 mmHg and/or DBP 80-89 mmHg.Results: The overall prevalence of prehypertension was 16.5%. The high exposure group had a higher prevalence of prehypertension compared to the low exposure group (20.6% vs. 11.8%, 1-tailed p = 0.049). After adjustment for potential confounders, the prevalence odds ratio (POR) for prehypertension was 2.3 [95% Confidence Interval (CI): 0.78-7.1, 1-tailed p=0.066] in the participants exposed to arsenic >400 µg/L in their early life. The increased prevalence of prehypertension was only evident in females (POR=8.8, 95% CI: 1.05-74.1, 1-tailed p=0.023), and not in males (POR= 1.1, 95% CI: 0.26-5.1, 1-tailed p=0.433).Conclusions: Our result suggests a possible effect of early life arsenic exposure on increased risk of prehypertension in females. We plan to follow this unique cohort to see if the effect on blood pressure persists in females as they grow older.

Background: The prevalence of type 2 diabetes (T2D) has nearly doubled since 1980. Elevated body mass index (BMI) is the leading risk factor for T2D, mediated by inflammation and oxidative stress. Arsenic shares similar pathogenic processes, and may contribute to hyperglycemia and beta-cell dysfunction. Objectives: We assessed a unique situation of individuals living in Northern Chile with data on lifetime arsenic exposure to evaluate the relationship between arsenic and T2D, and investigate possible interactions with BMI. Methods: We analyzed data collected from October 2007-December 2010 from an arsenic-cancer case-control study. Information on self-reported weight, height, smoking, diet, and other factors were obtained. Diabetes was defined by self-reported physician-diagnoses or use of hypoglycemic medication. A total of 1053 individuals, 234 diabetics and 819 without known diabetes were included. Results: The T2D odds ratio (OR) for cumulative arsenic exposures of 610-5279 and >= 5280 mu g/L-years occurring 40 years or more before interview were 0.97 (95% CI: 0.66-1.43) and 1.53 (95% CI: 1.05-2.23), respectively. Arsenic-associated T2D ORs were greater in subjects with increased BMIs. For example, the ORs for past cumulative exposures >= 5280 mu g/L-years was 1.45 (95% CI: 0.74-2.84) in participants with BMIs < 25 kg/m(2) but 2.64 (95% CI: 1.14-6.11) in those with BMIs >= 30 kg/m(2) (synergy index = 2.49, 95% CI: 0.87-7.09). Results were similar when people with cancer were excluded. Conclusions: These findings identify increased odds of T2D with arsenic exposure, which are significantly increased in individuals with excess BMI.

Background/Aim: The city of Antofagasta, the major city in northern Chile, had a specific period (1958-1970) with very high arsenic water concentrations of around 870 ug/L. We previously reported increased mortality associated with this arsenic exposure for 1981-2000, and separately for 2001-2010. In this paper, we compare bladder cancer mortality in Antofagasta with the that of the rest of Chile between these two periods.Methods: The age and gender specific numbers of bladder cancer deaths in Antofagasta were compared with expected numbers based on the rest of Chile for the two periods 1989-2000 and 2001-2010, and Standardized Mortality Ratios (SMRs) and attributable risks were estimated. We also made comparisons between different birth cohorts.Results: The overall SMRs for bladder cancer for Antofagasta were 8.8 (95% CI, 7.9-9.8) in 1989-2000, and 6.2 (95% CI, 5.6-6.9) in 2001-2010. The attributable risks among the exposed were 89% and 84%, with 296 bladder cancer deaths attributable to arsenic in the period 1989-2000, and 280 in the period 2001-2010. For those in the 1958-1970 birth cohort, who if born in Antofagasta would have experienced very high early life exposure, the SMRs were 38.3 (17.5-72.7) in 1989-2000 and 16.0 (10.1, 25.4) in 2001-2010.Conclusions: The relationship between arsenic in drinking water and subsequent bladder cancer mortality is quite extraordinary and without precedent in environmental epidemiology, including major impact among those who probably experienced early life exposure.

Background Region II in northern Chile (population 442 570) experienced a sudden major increase in arsenic water concentrations in 1958 in the main city of Antofagasta, followed by a major reduction in exposure when an arsenic removal plant was installed in 1970. It provides a unique opportunity to study latency effects of exposure to arsenic, and this is the first study with mortality data up to 40 years after exposure reduction. Methods We previously identified high mortality rates in Region II up to the year 2000. Here we present rate ratios (RRs) for Region II compared with all the rest of Chile from 2001 to 2010, and with unexposed Region V (population 1 539 852) for all years from 1950 to 2010. All statistical tests were one-sided. Results From 2001 to 2010, comparing Region II with the rest of Chile, lung and bladder mortality were still greatly elevated (RR = 3.38, 95% confidence interval [CI] = 3.19 to 3.58, P < .001 for lung cancer in men; RR = 2.41, 95% CI = 2.20 to 2.64, P < .001 for lung cancer in women; RR = 4.79, 95% CI = 4.20 to 5.46, P < .001 for bladder cancer in men; RR = 6.43, 95% CI = 5.49 to 7.54, P < .001 for bladder cancer in women). Kidney cancer mortality was also elevated (RR = 1.75, 95% CI = 1.49 to 2.05, P < .001 for men; RR = 2.09, 95% CI = 1.69 to 2.57, P < .001 for women). Earlier short latency acute myocardial infarction mortality increases had subsided. Conclusions Lung, bladder, and kidney cancer mortality due to arsenic exposure have very long latencies, with increased risks manifesting 40 years after exposure reduction. Our findings suggest that arsenic in drinking water may involve one of the longest cancer latencies for a human carcinogen.

Inter‐individual differences in arsenic metabolism have been linked to arsenic‐related disease risks. Arsenic (+3) methyltransferase (AS3MT) is the primary enzyme involved in arsenic metabolism, and we previously demonstrated in vitro that N‐6 adenine‐specific DNA methyltransferase 1 (N6AMT1) also methylates the toxic inorganic arsenic (iAs) metabolite, monomethylarsonous acid (MMA), to the less toxic dimethylarsonic acid (DMA). Here, we evaluated whether AS3MT and N6AMT1 gene polymorphisms alter arsenic methylation and impact iAs‐related cancer risks. We assessed AS3MT and N6AMT1 polymorphisms and urinary arsenic metabolites (%iAs, %MMA, %DMA) in 722 subjects from an arsenic‐cancer case‐control study in a uniquely exposed area in northern Chile. Polymorphisms were genotyped using a custom designed multiplex, ligation‐dependent probe amplification (MLPA) assay for 6 AS3MT SNPs and 14 tag SNPs in the N6AMT1 gene. We found several AS3MT polymorphisms associated with both urinary arsenic metabolite profiles and cancer risk. For example, compared to wildtypes, individuals carrying minor alleles in AS3MT rs3740393 had lower %MMA (mean difference = −1.9%, 95% CI: −3.3, −0.4), higher %DMA (mean difference = 4.0%, 95% CI: 1.5, 6.5), and lower odds ratios for bladder (OR = 0.3; 95% CI: 0.1–0.6) and lung cancer (OR = 0.6; 95% CI: 0.2–1.1). Evidence of interaction was also observed for both lung and bladder cancer between these polymorphisms and elevated historical arsenic exposures. Clear associations were not seen for N6AMT1. These results are the first to demonstrate a direct association between AS3MT polymorphisms and arsenic‐related internal cancer risk. This research could help identify subpopulations that are particularly vulnerable to arsenic‐related disease. Environ. Mol. Mutagen. 58:411–422, 2017. © 2017 Wiley Periodicals, Inc.

BACKGROUND:Elevated body mass index (BMI) and arsenic are both associated with cancer and with non-malignant lung disease. Using a unique exposure situation in Northern Chile with data on lifetime arsenic exposure, we previously identified the first evidence of an interaction between arsenic and BMI for the development of lung cancer. OBJECTIVES:We examined whether there was an interaction between arsenic and BMI for the development of non-malignant lung disease. METHODS:Data on lifetime arsenic exposure, respiratory symptoms, spirometry, BMI, and smoking were collected from 751 participants from cities in Northern Chile with varying levels of arsenic water concentrations. Spirometry values and respiratory symptoms were compared across subjects in different categories of arsenic exposure and BMI. RESULTS:Adults with both a BMI above the 90th percentile (>33.9kg/m2) and arsenic water concentrations ≥11µg/L exhibited high odds ratios (ORs) for cough (OR = 10.7, 95% confidence interval (CI): 3.03, 50.1), shortness of breath (OR = 14.2, 95% CI: 4.79, 52.4), wheeze (OR = 14.4, 95% CI: 4.80, 53.7), and the combined presence of any respiratory symptom (OR = 9.82, 95% CI: 4.22, 24.5). In subjects with lower BMIs, respiratory symptom ORs for arsenic water concentrations ≥11µg/L were markedly lower. In never-smokers, reductions in forced vital capacity associated with arsenic increased as BMI increased. Analysis of the FEV1/FVC ratio in never-smokers significantly increased as BMI and arsenic concentrations increased. Similar trends were not observed for FEV1 alone or in ever-smokers. CONCLUSIONS:This study provides preliminary evidence that BMI may increase the risk for arsenic-related non-malignant respiratory disease.

Background: Arsenic in drinking water has been associated with increases in lung disease, but information on the long-term impacts of early-life exposure or moderate exposure levels are limited.Methods: We investigated pulmonary disease and lung function in 795 subjects from three socio-demographically similar areas in northern Chile: Antofagasta, which had a well-described period of high arsenic water concentrations (860 mu g/L) from 1958 to 1970; Iquique, which had long-term arsenic water concentrations near 60 mu g/L; and Arica, with long-term water concentrations <= 10 mu g/L.Results: Compared to adults never exposed >10 mu g/L, adults born in Antofagasta during the high exposure period had elevated odds ratios (OR) of respiratory symptoms (e.g., OR for shortness of breath = 5.56, 90% confidence interval (CI): 2.68-11.5), and decreases in pulmonary function (e.g., 224 mL decrease in forced vital capacity in nonsmokers, 90% CI: 97-351 mL). Subjects with long-term exposure to arsenic water concentrations near 60 mu g/L also had increases in some pulmonary symptoms and reduced lung function.Conclusions: Overall, these findings provide new evidence that in utero or childhood arsenic exposure is associated with non-malignant pulmonary disease in adults. They also provide preliminary new evidence that longterm exposures to moderate levels of arsenic may be associated with lung toxicity, although the magnitude of these latter findings were greater than expected and should be confirmed. (C) 2016 Elsevier Inc. All rights reserved.

Background: A growing number of studies have identified an association between exposure to inorganic arsenic and hypertension. However, results have not been consistent across studies. Additional studies are warranted, given the global prevalence of both arsenic exposure and morbidity attributable to hypertension.Methods: We analyzed data collected from October 2007-December 2010 for a population-based cancer case control study in northern Chile. Data included lifetime individual arsenic exposure estimates and information on potential confounders for a total of 1266 subjects. Those self-reporting either a physician diagnosis of hypertension or use of an anti-hypertensive medication were classified as having hypertension (n=612). The association between hypertension and drinking water arsenic exposure was analyzed using logistic regression models.Results: Compared to those in the lowest category for lifetime highest 5-year average arsenic exposure (< 60 mu g/L), those in the middle (60-623 mu g/L) and upper (> 623 mu g/L) exposure categories had adjusted hypertension ORs of 1.49 (95% CI: 1.09, 2.05) and 1.65 (95% CI: 1.18, 2.32), respectively. Similar results were observed in analyses of lifetime cumulative exposures and analyses restricted to exposures from the distant past.Conclusions: We identified evidence of increased odds of hypertension with exposure to arsenic in drinking water among study participants. Our findings add to the growing body of research supporting this association, which could have important public health implications.

Introduction: Arsenic in drinking water can cause multiple health effects, including cancer, cardiovascular disease and chronic respiratory disease. The epidemiological evidence comes from populations with prolonged exposure above 100µg/L of inorganic arsenic in water. However, many recent publications claim to find health effects from drinking water containing less than 50µg/L of arsenic. This paper looks to see if they have characteristic validity-related features. Methods: We identified published studies conducted in populations where drinking water arsenic concentrations had been less than 50µg/L. We scored studies based on the following points, with 1 for good quality on each point and 0 if not. We totaled the scores for each study with a possible range of 0-7. 1. Did the authors discuss scientific plausibility of their findings at such low water concentrations? 2. Did the authors present their findings in a manner that made their implausibility apparent? 3. Was there evidence of increased risks in some simple stratified analyses? 4. Were key results from analyses confined to complex non-transparent statistical modeling? 5. Did exposure data span at least 20 years of measured drinking water concentrations? 6. Was exposure data confined to one point in time? 7. Was arsenic in water measured with sufficient latency before the outcomes? Results: 21 publications attributed chronic disease to arsenic in drinking water below 50µg/L. The average score was 1.5. Only one study scored above 3, and it had serious study design problems separate from the criteria addressed in our scoring. Conclusions: The studies claiming health effects of arsenic in populations whose drinking water contained less than 50µg/L have serious flaws. Greater rigor is needed in peer review of proposed studies and of publications involving low arsenic water concentrations. Regulatory agencies need to be very cautious about using these studies for risk assessment.

Objectives Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has inconsistently been associated with a decreased sex ratio of the offspring (number of male births divided by total births). We conducted a study among men and women who were employed in a New Zealand phenoxy herbicide production plant between 1969 and 1984, to study their offspring sex ratio in relation to their back-calculated TCDD serum concentrations determined in 2007/2008.Methods A total of 127 men and 21 women reported that 355 children were conceived after starting employment at the plant. The association between their lipid-standardised TCDD serum concentrations back-calculated to the time of their offspring's birth and the probability of a male birth was estimated through logistic regression, adjusting for the age of the exposed parent at birth, current body mass index and smoking.Results The overall sex ratio was 0.55 (197 boys, 158 girls). For fathers with serum TCDD concentrations >= 20 pg/g lipid at time of birth, the sex ratio was 0.47 (OR 0.49; 95% CI 0.30 to 0.79). The probability of a male birth decreased with higher paternal serum TCDD at time of birth (<4; 4-20; 20-100; >= 100 pg/g lipid), with ORs of 1.00 (reference); 1.00 (95% CI 0.50 to 2.02); 0.52 (95% CI 0.29 to 0.92); 0.45 (95% CI 0.23 to 0.89), p trend 0.007. For exposed mothers, the sex ratio was not reduced.Conclusions This study indicates that paternal serum TCDD concentrations in excess of an estimated 20 pg/g lipid at time of conception are associated with a reduced sex ratio.

Background: Millions of individuals worldwide, particularly those living in rural and developing areas, are exposed to harmful levels of inorganic arsenic (iAs) in their drinking water. Inorganic As exposure during key developmental periods is associated with a variety of adverse health effects, including those that are evident in adulthood. There is considerable interest in identifying the molecular mechanisms that relate early-life iAs exposure to the development of these latent diseases, particularly in relationship to cancer.Objectives: This work summarizes research on the molecular mechanisms that underlie the increased risk of cancer development in adulthood that is associated with early-life iAs exposure.Discussion: Epigenetic reprogramming that imparts functional changes in gene expression, the development of cancer stem cells, and immunomodulation are plausible underlying mechanisms by which early-life iAs exposure elicits latent carcinogenic effects.Conclusions: Evidence is mounting that relates early-life iAs exposure and cancer development later in life. Future research should include animal studies that address mechanistic hypotheses and studies of human populations that integrate early-life exposure, molecular alterations, and latent disease outcomes.

Background: Elevated body mass index (BMI) is a risk factor for cardiovascular disease, diabetes, cancer, and other diseases. Inflammation or oxidative stress induced by high BMI may explain some of these effects. Millions of people drink arsenic-contaminated water worldwide, and ingested arsenic has also been associated with inflammation, oxidative stress, and cancer.Objectives: To assess the unique situation of people living in northern Chile exposed to high arsenic concentrations in drinking water and investigate interactions between arsenic and BMI, and associations with lung and bladder cancer risks.Methods: Information on self-reported body mass index (BMI) at various life stages, smoking, diet, and lifetime arsenic exposure was collected from 532 cancer cases and 634 population-based controls.Results: In subjects with BMIs < 90th percentile in early adulthood (27.7 and 28.6 kg/m(2) in males and females, respectively), odds ratios (OR) for lung and bladder cancer combined for arsenic concentrations of < 100, 100-800 and > 800 mu g/L were 1.00, 1.64 (95% CI, 1.19-227), and 3.12 (2.30-4.22). In subjects with BMIs >= 90th percentile in early adulthood, the corresponding ORs were higher: 1.00, 1.84 (0.75-4.52), and 9.37 (2.88-30.53), respectively (synergy index=4.05, 95% Cl, 1.27-12.88). Arsenic-related cancer ORs > 20 were seen in those with elevated BMIs in both early adulthood and in later life. Adjustments for smoking, diet, and other factors had little impact.Conclusion: These findings provide novel preliminary evidence supporting the notion that environmentally-related cancer risks may be markedly increased in people with elevated BMIs, especially in those with an elevated BMI in early-life. (C) 2015 Elsevier Inc. All rights reserved.