Government laboratory worker with lung cancer: comparing risks from beryllium, asbestos, and tobacco smoke.

Occupational medicine physicians are frequently asked to establish cancer causation in patients with both workplace and non-workplace exposures. This is especially difficult in cases involving beryllium for which the data on human carcinogenicity are limited and controversial. In this report we present the case of a 73-year-old former technician at a government research facility who was recently diagnosed with lung cancer. The patient is a former smoker who has worked with both beryllium and asbestos. He was referred to the University of California, San Francisco, Occupational and Environmental Medicine Clinic at San Francisco General Hospital for an evaluation of whether past workplace exposures may have contributed to his current disease. The goal of this paper is to provide an example of the use of data-based risk estimates to determine causation in patients with multiple exposures. To do this, we review the current knowledge of lung cancer risks in former smokers and asbestos workers, and evaluate the controversies surrounding the epidemiologic data linking beryllium and cancer. Based on this information, we estimated that the patient's risk of lung cancer from asbestos was less than his risk from tobacco smoke, whereas his risk from beryllium was approximately equal to his risk from smoking. Based on these estimates, the patient's workplace was considered a probable contributing factor to his development of lung cancer

Case-control study of arsenic in drinking water and lung cancer in California and Nevada.

Millions of people are exposed to arsenic in drinking water, which at high concentrations is known to cause lung cancer in humans. At lower concentrations, the risks are unknown. We enrolled 196 lung cancer cases and 359 controls matched on age and gender from western Nevada and Kings County, California in 2002-2005. After adjusting for age, sex, education, smoking and occupational exposures, odds ratios for arsenic concentrations ≥85 µg/L (median = 110 µg/L, mean = 173 µg/L, maximum = 1,460 µg/L) more than 40 years before enrollment were 1.39 (95% CI = 0.55-3.53) in all subjects and 1.61 (95% CI = 0.59-4.38) in smokers. Although odds ratios were greater than 1.0, these increases may have been due to chance given the small number of subjects exposed more than 40 years before enrollment. This study, designed before research in Chile suggested arsenic-related cancer latencies of 40 years or more, illustrates the enormous sample sizes needed to identify arsenic-related health effects in low-exposure countries with mobile populations like the U.S. Nonetheless, our findings suggest that concentrations near 100 µg/L are not associated with markedly high relative risks

Associations between arsenic (+3 oxidation state) methyltransferase (AS3MT) and N-6 adenine-specific DNA methyltransferase 1 (N6AMT1) polymorphisms, arsenic metabolism, and cancer risk in a chilean population

nter‐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

Arsenic in drinking water and cerebrovascular disease, diabetes mellitus, and kidney disease in Michigan: a standardized mortality ratio analysis

BACKGROUND: Exposure to arsenic concentrations in drinking water in excess of 300 μg/L is associated with diseases of the circulatory and respiratory system, several types of cancer, and diabetes; however, little is known about the health consequences of exposure to low-to-moderate levels of arsenic (10–100 μg/L). METHODS: A standardized mortality ratio (SMR) analysis was conducted in a contiguous six county study area of southeastern Michigan to investigate the relationship between moderate arsenic levels and twenty-three selected disease outcomes. Disease outcomes included several types of cancer, diseases of the circulatory and respiratory system, diabetes mellitus, and kidney and liver diseases. Arsenic data were compiled from 9251 well water samples tested by the Michigan Department of Environmental Quality from 1983 through 2002. Michigan Resident Death Files data were amassed for 1979 through 1997 and sex-specific SMR analyses were conducted with indirect adjustment for age and race; 99% confidence intervals (CI) were reported. RESULTS: The six county study area had a population-weighted mean arsenic concentration of 11.00 μg/L and a population-weighted median of 7.58 μg/L. SMR analyses were conducted for the entire six county study area, for only Genesee County (the most populous and urban county), and for the five counties besides Genesee. Concordance of results across analyses is used to interpret the findings. Elevated mortality rates were observed for both males (M) and females (F) for all diseases of the circulatory system (M SMR, 1.11; CI, 1.09–1.13; F SMR, 1.15; CI, 1.13,-1.17), cerebrovascular diseases (M SMR, 1.19; CI, 1.14–1.25; F SMR, 1.19; CI, 1.15–1.23), diabetes mellitus (M SMR, 1.28; CI, 1.18–1.37; F SMR, 1.27; CI, 1.19–1.35), and kidney diseases (M SMR, 1.28; CI, 1.15–1.42; F SMR, 1.38; CI, 1.25–1.52). CONCLUSION: This is some of the first evidence to suggest that exposure to low-to-moderate levels of arsenic in drinking water may be associated with several of the leading causes of mortality, although further epidemiologic studies are required to confirm the results suggested by this ecologic SMR analysis

Water quality monitoring records for estimating tap water arsenic and nitrate: a validation study

<p>Abstract</p> <p>Background</p> <p>Tap water may be an important source of exposure to arsenic and nitrate. Obtaining and analyzing samples in the context of large studies of health effects can be expensive. As an alternative, studies might estimate contaminant levels in individual homes by using publicly available water quality monitoring records, either alone or in combination with geographic information systems (GIS).</p> <p>Methods</p> <p>We examined the validity of records-based methods in Washington State, where arsenic and nitrate contamination is prevalent but generally observed at modest levels. Laboratory analysis of samples from 107 homes (median 0.6 μg/L arsenic, median 0.4 mg/L nitrate as nitrogen) served as our "gold standard." Using Spearman's rho we compared these measures to estimates obtained using only the homes' street addresses and recent and/or historical measures from publicly monitored water sources within specified distances (radii) ranging from one half mile to 10 miles.</p> <p>Results</p> <p>Agreement improved as distance decreased, but the proportion of homes for which we could estimate summary measures also decreased. When including all homes, agreement was 0.05-0.24 for arsenic (8 miles), and 0.31-0.33 for nitrate (6 miles). Focusing on the closest source yielded little improvement. Agreement was greatest among homes with private wells. For homes on a water system, agreement improved considerably if we included only sources serving the relevant system (ρ = 0.29 for arsenic, ρ = 0.60 for nitrate).</p> <p>Conclusions</p> <p>Historical water quality databases show some promise for categorizing epidemiologic study participants in terms of relative tap water nitrate levels. Nonetheless, such records-based methods must be used with caution, and their use for arsenic may be limited.</p

Intakes of fruits and vegetables, carotenoids and vitamins A, E, C in relation to the risk of bladder cancer in the ATBC cohort study

We examined the relation between dietary fruit and vegetables, carotenoids and vitamin intakes and the risk of bladder cancer among male smokers in a prospective cohort study. Over a median of 11 years, we followed 27 111 male smokers aged 50–69 years who were initially enrolled in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study. During this period, 344 men developed bladder cancer. All of these men had completed a 276-food item dietary questionnaire at baseline. Cox proportional hazards models were used to estimate the relative risks and 95% confidence intervals and to simultaneously adjust for age, smoking history, energy intake and intervention group. Consumption of fruits and vegetables was not associated with the risk of bladder cancer (relative risk=1.28; 95% confidence intervals CI: 0.89–1.84, for highest vs lowest quintile). Similarly, no associations were observed for groups of fruits or vegetables (berries and cruciferous vegetables), or for specific fruits and vegetables. Dietary intakes of alpha-carotene, beta-carotene, lycopene, lutein/zeaxanthin, beta-cryptoxanthin, vitamins A, E, and C, and folate were not related to the risk of bladder cancer. These findings suggest that fruit and vegetable intakes are not likely to be associated with bladder cancer risk. However, these results may not be generalisable to non-smokers

Dietary intake of micronutrients and the risk of developing bladder cancer: results from the Belgian case–control study on bladder cancer risk

OBJECTIVE: We aimed to investigate the effect of dietary intake of micronutrients that are metabolized and excreted via the urinary tract on bladder cancer risk. METHODS: A semi-quantitative 322 item food frequency questionnaire (FFQ) was used to collect dietary data from 200 bladder cancer cases and 386 control subjects participating in the Belgian case-control study on bladder cancer risk. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression adjusting for age, sex, smoking characteristics, occupational exposures, and energy intake. RESULTS: We observed a positive association between calcium intake and bladder cancer (OR: 1.77; 95% CI: 1.00-3.15; p-trend = 0.049) and increased odds, although not statistically significant, for highest tertile of phosphorus intake (OR: 1.82; 95% CI: 0.95-3.49; p-trend = 0.06). We identified possible modification of the effects of both calcium and phosphorus by level of magnesium intake. Increased odds of bladder cancer were also observed for participants with highest intake of phosphorus and lowest intake of vitamin D (OR: 4.25; 95% CI: 1.44-12.55) and among older participants with the highest intakes of calcium (OR: 1.90; 95% CI: 1.08-3.36) and phosphorus (OR: 2.02; 95% CI: 1.05-3.92). CONCLUSION: The positive associations we observed between bladder cancer and intake of calcium and phosphorus require confirmation by other studies. The balances between inter-related micronutrients also warrant further examination