Colorectal Cancer and Long-Term Exposure to Trihalomethanes in Drinking Water: A Multicenter Case-Control Study in Spain and Italy.

BACKGROUND: Evidence on the association between colorectal cancer and exposure to disinfection by-products in drinking water is inconsistent. OBJECTIVES: We assessed long-term exposure to trihalomethanes (THMs), the most prevalent group of chlorination by-products, to evaluate the association with colorectal cancer. METHODS: A multicenter case-control study was conducted in Spain and Italy in 2008-2013. Hospital-based incident cases and population-based (Spain) and hospital-based (Italy) controls were interviewed to ascertain residential histories, type of water consumed in each residence, frequency and duration of showering/bathing, and major recognized risk factors for colorectal cancer. We estimated adjusted odds ratios (OR) for colorectal cancer in association with quartiles of estimated average lifetime THM concentrations in each participant's residential tap water (micrograms/liter; from age 18 to 2 years before the interview) and estimated average lifetime THM ingestion from drinking residential tap water (micrograms/day). RESULTS: We analyzed 2,047 cases and 3,718 controls. Median values (ranges) for average lifetime residential tap water concentrations of total THMs, chloroform, and brominated THMs were 30 (0-174), 17 (0-63), and 9 (0-145) µg/L, respectively. Total THM concentration in residential tap water was not associated with colorectal cancer (OR = 0.92, 95% CI: 0.66, 1.28 for highest vs. lowest quartile), but chloroform concentrations were inversely associated (OR = 0.31, 95% CI: 0.24, 0.41 for highest vs. lowest quartile). Brominated THM concentrations showed a positive association among men in the highest versus the lowest quartile (OR = 1.43, 95% CI: 0.83, 2.46). Patterns of association were similar for estimated average THM ingestion through residential water consumption. CONCLUSIONS: We did not find clear evidence of an association between detailed estimates of lifetime total THM exposure and colorectal cancer in our large case-control study population. Negative associations with chloroform concentrations and ingestion suggest differences among specific THMs, but these findings should be confirmed in other study populations. Citation: Villanueva CM, Gracia-Lavedan E, Bosetti C, Righi E, Molina AJ, Martín V, Boldo E, Aragonés N, Perez-Gomez B, Pollan M, Gomez Acebo I, Altzibar JM, Jiménez Zabala A, Ardanaz E, Peiró R, Tardón A, Chirlaque MD, Tavani A, Polesel J, Serraino D, Pisa F, Castaño-Vinyals G, Espinosa A, Espejo-Herrera N, Palau M, Moreno V, La Vecchia C, Aggazzotti G, Nieuwenhuijsen MJ, Kogevinas M. 2017. Colorectal cancer and long-term exposure to trihalomethanes in drinking water: a multicenter case---control study in Spain and Italy. Environ Health Perspect 125:56-65; http://dx.doi.org/10.1289/EHP155.

Ingested Nitrate and Breast Cancer in the Spanish Multicase-Control Study on Cancer (MCC-Spain).

BACKGROUND: Ingested nitrate leads to endogenous formation of N-nitroso compounds that are breast carcinogens in animals, but human evidence is limited. OBJECTIVE: We evaluated ingested nitrate as a risk factor for breast cancer (BC) in a multicase-control study. METHODS: Hospital-based incident BC cases and population-based controls were recruited in eight Spanish regions in 2008-2013; participants provided residential and water consumption from 18 years of age and information on known BC risk factors. Long-term nitrate levels (1940-2010) were estimated and linked with residential histories and water consumption to calculate waterborne ingested nitrate (milligrams/day). Dietary ingested nitrate (milligrams/day) was calculated using food frequency questionnaires and published dietary nitrate contents. Interactions with endogenous nitrosation factors and other variables were evaluated. A total of 1,245 cases and 1,520 controls were included in the statistical analysis. RESULTS: Among the study regions, average ± SD waterborne ingested nitrate ranged from 2.9 ± 1.9 to 13.5 ± 7.5 mg/day, and dietary ingested nitrate ranged from 88.5 ± 48.7 to 154 ± 87.8 mg/day. Waterborne ingested nitrate was not associated with BC overall, but among postmenopausal women, those with both high nitrate (> 6 vs. < 2.6 mg/day) and high red meat intake (≥ 20 vs. < 20 g/day) were more likely to be cases than women with low nitrate and low red meat intake (adjusted odds ratio = 1.64; 95% confidence interval: 1.08, 2.49; overall interaction p-value = 0.17). No association was found with dietary nitrate. CONCLUSIONS: Waterborne ingested nitrate was associated with BC only among postmenopausal women with high red meat consumption. Dietary nitrate was not associated with BC regardless of the animal or vegetable source or of menopausal status. CITATION: Espejo-Herrera N, Gracia-Lavedan E, Pollan M, Aragonés N, Boldo E, Perez-Gomez B, Altzibar JM, Amiano P, Zabala AJ, Ardanaz E, Guevara M, Molina AJ, Barrio JP, Gómez-Acebo I, Tardón A, Peiró R, Chirlaque MD, Palau M, Muñoz M, Font-Ribera L, Castaño-Vinyals G, Kogevinas M, Villanueva CM. 2016. Ingested nitrate and breast cancer in the Spanish Multicase-Control Study on Cancer (MCC-Spain). Environ Health Perspect 124:1042-1049; http://dx.doi.org/10.1289/ehp.1510334.