Sylvaine Cordier

Disinfection byproducts and bladder cancer: a pooled analysis.

Background: Exposure to disinfection byproducts in drinking water has been associated with an increased risk of bladder cancer. We pooled the primary data from 6 case-control studies of bladder cancer that used trihalomethanes as a marker of disinfection byproducts. Methods: Two studies were included from the United States and one each from Canada, France, Italy, and Finland. Inclusion criteria were availability of detailed data on trihalomethane exposure and individual water consumption. The analysis included 2806 cases and 5254 controls, all of whom had measures of known exposure for at least 70% of the exposure window of 40 years before the interview. Cumulative exposure to trihalomethanes was estimated by combining individual year-by-year average trihalomethane level and daily tap water consumption. Results: There was an adjusted odds ratio (OR) of 1.24 in men exposed to an average of more than 1 μg/L (ppb) trihalomethanes compared with those who had lower or no exposure (95% confidence interval [CI] = 1.09–1.41). Estimated relative risks increased with increasing exposure, with an OR of 1.44 (1.20–1.73) for exposure higher than 50 μg/L (ppb). Similar results were found with other indices of trihalomethane exposure. Among women, trihalomethane exposure was not associated with bladder cancer risk (0.95; 0.76–1.20). Conclusions: These findings strengthen the hypothesis that the risk of bladder cancer is increased with long-term exposure to disinfection byproducts at levels currently observed in many industrialized countries.

Cigarette smoking and bladder cancer in men : A pooled analysis of 11 case-control studies

The primary risk factor for bladder cancer is cigarette smoking. Using a combined analysis of 11 case‐control studies, we have accurately measured the relationship between cigarette smoking and bladder cancer in men. Available smoking information on 2,600 male bladder cancer cases and 5,524 male controls included duration of smoking habit, number of cigarettes smoked per day and time since cessation of smoking habit for ex‐smokers. There was a linear increasing risk of bladder cancer with increasing duration of smoking, ranging from an odds ratio (OR) of 1.96 after 20 years of smoking (95% confidence interval [CI] 1.48–2.61) to 5.57 after 60 years (CI 4.18–7.44). A dose relationship was observed between number of cigarettes smoked per day and bladder cancer up to a threshold limit of 15–20 cigarettes per day, OR = 4.50 (CI 3.81–5.33), after which no increased risk was observed. An immediate decrease in risk of bladder cancer was observed for those who gave up smoking. This decrease was over 30% after 1–4 years, OR = 0.65 (0.53–0.79), and was over 60% after 25 years of cessation, OR = 0.37 (0.30–0.45). However, even after 25 years, the decrease in risk did not reach the level of the never‐smokers, OR = 0.20. (0.17–0.24). The proportion of bladder cancer cases attributable to ever‐smoking was 0.66 (0.61–0.70) for all men and 0.73 (0.66–0.79) for men younger than 60. These estimates are higher than previously calculated. Int. J. Cancer 86:289–294, 2000.

Exposure to Phthalates and Phenols during Pregnancy and Offspring Size at Birth

Background: Data concerning the effects of prenatal exposures to phthalates and phenols on fetal growth are limited in humans. Previous findings suggest possible effects of some phenols on male birth weight. Objective: Our aim was to assess the relationships between prenatal exposures to phthalates and phenols and fetal growth among male newborns. Methods: We conducted a case–control study on male malformations of the genitalia nested in two French mother–child cohorts with recruitment between 2002 and 2006. We measured, in maternal urinary samples collected between 6 and 30 gestational weeks, the concentrations (micrograms per liter) of 9 phenol (n = 191 pregnant women) and 11 phthalate metabolites (n = 287). Weight, length, and head circumference at birth were collected from maternity records. Statistical analyses were corrected for the oversampling of malformation cases. Results: Adjusted birth weight decreased by 77 g [95% confidence interval (CI): –129, –25] and by 49 g (95% CI: –86, –13) in association with a 1-unit increase in ln-transformed 2,4-dichlorophenol (DCP) and 2,5-DCP urinary concentrations, respectively. Benzophenone-3 (BP3) ln-transformed concentrations were positively associated with weight (26 g; 95% CI: –2, 54) and head circumference at birth (0.1 cm; 95% CI: 0.0, 0.2). Head circumference increased by 0.3 cm (95% CI: 0.0, 0.7) in association with a 1-unit increase in ln-transformed BPA concentration. For phthalate metabolites there was no evidence of monotonic associations with birth weight. Conclusions: Consistent with findings of a previous study, we observed evidence of an inverse association of 2,5-DCP and a positive association of BP3 with male birth weight.

Occupation and bladder cancer among men in Western Europe

Objectives: We examined which occupations and industries are currently at high risk for bladder cancer in men. Methods: We combined data from 11 case–control studies conducted between 1976–1996 in six European countries. The study comprised 3346 incident cases and 6840 controls, aged 30–79 years. Lifetime occupational and smoking histories were examined using common coding. Results: Odds ratios for eight a priori defined high-risk occupations were low, and with the exception of metal workers and machinists (OR = 1.16, 95% CI = 1.02–1.32), were not statistically significant. Higher risks were observed for specific categories of painters, metal, textile and electrical workers, for miners, transport operators, excavating-machine operators, and also for non-industrial workers such as concierges and janitors. Industries entailing a high risk included salt mining, manufacture of carpets, paints, plastics and industrial chemicals. An increased risk was found for exposure to PAHs (OR for highest exposure tertile = 1.23, 95% CI = 1.07–1.4). The risk attributable to occupation ranged from 4.2 to 7.4%, with an estimated 4.3% for exposure to PAHs. Conclusions: Metal workers, machinists, transport equipment operators and miners are among the major occupations contributing to occupational bladder cancer in men in Western Europe. In this population one in 10 to one in 20 cancers of the bladder can be attributed to occupation.

The Faroes statement: Human Health effects of developmental exposure to chemicals in our environment

The periods of embryonic, foetal and infant developmentare remarkably susceptible to environmental hazards. Toxicexposures to chemical pollutants during these windows ofincreased susceptibility can cause disease and disability ininfants, children and across the entire span of human life.Among the effects of toxic exposures recognized in the pasthave been spontaneous abortion, congenital malformations,lowered birthweight and other adverse effects. These outcomesmay be readily apparent. However, even subtle changes causedby chemical exposures during early development may leadto important functional deficits and increased risks ofdisease later in life. The timing of exposure during early lifehas therefore become a crucial factor to be considered intoxicological assessments.During 20–24 May 2007, researchers in the fields of environmentalhealth, environmental chemistry, developmentalbiology, toxicology, epidemiology, nutrition and paediatricsgathered at the International Conference on Fetal Programmingand Developmental Toxicity, in Torshavn, FaroeIslands. The conference goal was to highlight new insightsinto the effects of prenatal and early postnatal exposure tochemical agents, and their sustained effects on the individualthroughout the lifespan. The conference brought togetherresearchers to focus on human data and the translationof laboratory results to elucidate the environmental risks tohuman health.

Chlordecone Exposure and Risk of Prostate Cancer

PURPOSE Determining whether environmental estrogens are associated with the risk of prostate cancer may have important implications for our general understanding of this disease. The estrogenic insecticide chlordecone was used extensively in the French West Indies, contaminating the population for more than 30 years. We analyzed the relationship between exposure to chlordecone and the risk of prostate cancer. PATIENTS AND METHODS We investigated 623 men with prostate cancer and 671 controls. Exposure was analyzed according to case-control status, using either current plasma concentration or a cumulative exposure index based on years of exposure. We genotyped two single-nucleotide polymorphisms (rs3829125 and rs17134592) in the gene encoding chlordecone reductase. RESULTS We found a significant increase in the risk of prostate cancer with increasing plasma chlordecone concentration (odds ratio [OR], 1.77; 95% CI, 1.21 to 2.58 for the highest tertile of values above the limit of detection [LD]; P trend = .002) and for cumulative exposure index (OR, 1.73; 95% CI, 1.04 to 2.88 for the highest quartile; P trend = .004). Stronger associations were observed among those with a positive family history of prostate cancer and among those who had lived in a Western country. The rs3829125 and rs17134592 allele variants were in complete linkage disequilibrium and were found at low frequency (0.04). Among subjects with plasma chlordecone concentrations above the LD, carriers of the allele variants had a higher risk of prostate cancer (OR, 5.23; 95% CI, 0.82 to 33.32). CONCLUSION These findings support the hypothesis that exposure to environmental estrogens increases the risk of prostate cancer.

Tobacco and Alcohol Use During Pregnancy and Risk of Oral Clefts

OBJECTIVES This study examined the relationship between maternal tobacco and alcohol consumption during the first trimester of pregnancy and oral clefts. METHODS Data were derived from a European multicenter case-control study including 161 infants with oral clefts and 1134 control infants. RESULTS Multivariate analyses showed an increased risk of cleft lip with or without cleft palate associated with smoking (odds ratio [OR] = 1.79, 95% confidence interval [CI] = 1.07, 3.04) and an increased risk of cleft palate associated with alcohol consumption (OR = 2.28, 95% CI = 1.02, 5.09). The former risk increased with the number of cigarettes smoked. CONCLUSIONS This study provides further evidence of the possible role of prevalent environmental exposures such as tobacco and alcohol in the etiology of oral clefts.

The contribution of cigarette smoking to bladder cancer in women (pooled European data).

AbstractBackground: Using a combined analysis of 11 case–control studies from Europe, we have investigated the relationship between cigarette smoking and bladder cancer in women. Methods: Available smoking information on 685 female bladder cancer cases and 2416 female controls included duration of smoking habit, number of cigarettes smoked per day, and time since cessation of smoking habit for ex-smokers. Results: There was an increasing risk of bladder cancer with increasing duration of smoking, ranging from approximately a two-fold increased risk for a duration of less than 10 years (odds ratio (OR) = 1.9, 95% confidence interval (CI) 1.1–3.1) to over a four-fold increased risk for a duration of greater than 40 years (OR = 4.1, 95% CI 3.0–5.5). A dose–response relationship was observed between number of cigarettes smoked per day and bladder cancer up to a threshold limit of 15–20 cigarettes per day, OR = 3.8 (95% CI 2.7–5.4), after which no increased risk was observed. An immediate decrease in risk of bladder cancer was observed for those who gave up smoking. This decrease was over 30% in the immediate 1–4 years after cessation, OR = 0.68 (95% CI 0.38–1.2). However, even after 25 years the decrease in risk did not reach the level of the never-smokers, OR = 0.27 (95% CI 0.21–0.35). Conclusion: The proportion of bladder cancer cases among women attributable to ever smoking was 0.30, (0.25–0.35) and to current smoking was 0.18 (0.14–0.22). These attributable proportions are less than those observed among men, although they are likely to increase in the future as the smoking-related disease epidemic among women matures.

Total and specific fluid consumption as determinants of bladder cancer risk

We pooled the data from 6 case‐control studies of bladder cancer with detailed information on fluid intake and water pollutants, particularly trihalomethanes (THM), and evaluated the bladder cancer risk associated with total and specific fluid consumption. The analysis included 2,729 cases and 5,150 controls. Odds ratios (OR) and 95% confidence intervals (CI) for fluid consumption were adjusted for age, gender, study, smoking status, occupation and education. Total fluid intake was associated with an increased risk of bladder cancer in men. The adjusted OR for 1 l/day increase in intake was 1.08, (95% CI 1.03–1.14, p‐value for linear trend <0.001), while no trend was observed in women (OR = 1.04, 0.94–1.15; p‐value = 0.7). OR was 1.33 (1.12–1.58) for men in the highest category of intake (>3.5 l/day) as compared to those in the lowest (≤2 l/day). An increased risk was associated with intake of tap water. OR for >2 l/day vs. ≤0.5 l/day was 1.46 (1.20–1.78), with a higher risk among men (OR = 1.50, 1.21–1.88). No increased risk was observed for the same intake groups of nontap water in men (OR = 0.97, 0.77–1.22) or in women (OR = 0.85, 0.50–1.42). Increased bladder cancer risks were observed for an intake of >5 cups of coffee daily vs. <5 and for THM exposure, but neither exposure confounded or modified the OR for tap water intake. The association of bladder cancer with tap water consumption, but not with nontap water fluids, suggests that carcinogenic chemicals in tap water may explain the increased risk.

Assessing exposure and health consequences of chemicals in drinking water : Current state of knowledge and research needs

Background: Safe drinking water is essential for well-being. Although microbiological contamination remains the largest cause of water-related morbidity and mortality globally, chemicals in water supplies may also cause disease, and evidence of the human health consequences is limited or lacking for many of them. Objectives: We aimed to summarize the state of knowledge, identify gaps in understanding, and provide recommendations for epidemiological research relating to chemicals occurring in drinking water. Discussion: Assessing exposure and the health consequences of chemicals in drinking water is challenging. Exposures are typically at low concentrations, measurements in water are frequently insufficient, chemicals are present in mixtures, exposure periods are usually long, multiple exposure routes may be involved, and valid biomarkers reflecting the relevant exposure period are scarce. In addition, the magnitude of the relative risks tends to be small. Conclusions: Research should include well-designed epidemiological studies covering regions with contrasting contaminant levels and sufficient sample size; comprehensive evaluation of contaminant occurrence in combination with bioassays integrating the effect of complex mixtures; sufficient numbers of measurements in water to evaluate geographical and temporal variability; detailed information on personal habits resulting in exposure (e.g., ingestion, showering, swimming, diet); collection of biological samples to measure relevant biomarkers; and advanced statistical models to estimate exposure and relative risks, considering methods to address measurement error. Last, the incorporation of molecular markers of early biological effects and genetic susceptibility is essential to understand the mechanisms of action. There is a particular knowledge gap and need to evaluate human exposure and the risks of a wide range of emerging contaminants. Citation: Villanueva CM, Kogevinas M, Cordier S, Templeton MR, Vermeulen R, Nuckols JR, Nieuwenhuijsen MJ, Levallois P. 2014. Assessing exposure and health consequences of chemicals in drinking water: current state of knowledge and research needs. Environ Health Perspect 122:213–221; http://dx.doi.org/10.1289/ehp.1206229