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

Abstract

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.

Figure 1

Distribution of average residential trihalomethane (THM) exposure among subjects with THM estimates for ≥ 70% of the exposure window (age 18 to 2 years before the interview) from reliable interviews. (A) Average concentrations at the tap (micrograms/liter), n = 5,291. (B) Average ingested levels (micrograms/day), n = 5,731. All areas correspond to Spain except Milano and Pordenone/Udine (Italy). Boxes are delimited by the 25th (left hinge) and 75th (right hinge) percentiles, the central vertical line represents the median value, the whiskers represent ± 1.5 times the interquartile range, and the points outside the whiskers represent outliers.

Figure 2

Exposure–response relationship between residential trihalomethane (THM) concentrations (x-axis, in micrograms/liter) and colorectal cancer (y-axis, expressed as odds ratios, ORs) among 1,837 cases and 3,454 controls. (A) Men. (B) Women. Smoothed spline with 3 degrees of freedom from general additive models adjusted for sex, age, area, education, smoking, physical activity, nonsteroidal antiinflammatory drug use, and family history of cancer. Subjects with unsatisfactory questionnaires and subjects with THMs estimated for < 70% of the exposure window were excluded. p-Value gain compared with linearity is < 0.001 for all models, except for chloroform in women (p-value = 0.38). Tick marks above the x-axes represent observations, and the dashed lines represent the 95% confidence intervals (CIs).