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Two Studies on Disinfection Byproducts in Drinking Water and Cancer Risk

, by Elise Tookmanian, Ph.D.

Water fills a clear cup from a faucet.

Disinfectants, like chlorine, are often used during the normal course of public water treatment. These chemicals can react with organic matter in wastewater to create byproducts, such as trihalomethanes (THMs). Some of these compounds have been classified as probable human carcinogens by the International Agency for Research on Cancer. Several epidemiologic studies have linked THMs to bladder cancer risk, but the evidence is limited for endometrial cancer. DCEG researchers in the Occupational and Environmental Epidemiology branch (OEEB) investigated the interaction between disinfection byproducts and genetic variation in bladder cancer and described a new association between disinfection byproducts and endometrial cancer. These studies were published in Environmental Health Perspectives in May 2022.  

Laura Beane Freeman, Ph.D., senior investigator in OEEB, and colleagues, investigated gene-environment interactions using data from two large case-control studies: the population-based New England Bladder Cancer Study and the hospital-based Spanish Bladder Cancer Study. Out of 16 bladder cancer susceptibility genetic variants discovered through genome-wide association studies, Dr. Beane Freeman identified a single nucleotide polymorphism (SNP) at locus rs907611 at 11p15.5 in the LSP1 region that was most strongly associated with risk of bladder cancer with higher exposure to THMs in drinking water in both studies.  Specifically, the risk was highest in those with the GG genotype.  

LSP1 is responsible for recruiting leukocytes to inflamed sites, leading the researchers to hypothesize that exposure to THMs for people with the GG genotype may exacerbate bladder inflammation, which may in turn increase risk of bladder cancer. More mechanistic research into these interactions is needed.  

Rena Jones, Ph.D., M.S., investigator in OEEB, led the study on disinfectant byproducts in drinking water and endometrial cancer risk in postmenopausal women in the Iowa Women’s Health Study cohort. The previous epidemiological evidence for this association is limited, but experimental evidence points to hormone disruption, which is known to be associated with endometrial cancer risk.   

Compared to previous work, this study was aided by an improved drinking water exposure assessment and included over 20 years of follow-up of study participants. In addition to THMs, they evaluated another group of disinfection byproducts that have been less frequently studied in relation to cancer—haloacetic acids. 

The investigators discovered a novel association between consumption of drinking water with higher concentrations of these disinfection byproducts and endometrial cancer risk. Additionally, participants who reported ever use of hormone replacement therapy (HRT) and were exposed to THMs had a higher risk of endometrial cancer compared to non-HRT users. This finding fits with prior observations of an association between hormone disruption and endometrial cancer risk, specifically increased estrogen levels.  

The study also quantified nitrate and nitrite exposure from both drinking water and diet but did not observe associations with endometrial cancer risk.  

The Environmental Protection Agency regulates public water systems and provides information on drinking water to the public.  


1. Beane Freeman L, et al. Disinfection By-Products in Drinking Water and Bladder Cancer: Evaluation of Risk Modification by Common Genetic Polymorphisms in Two Case–Control Studies. Environ Health Perspect. 2022.

2. Medgyesi DN, et al. Drinking Water Disinfection Byproducts, Ingested Nitrate, and Risk of Endometrial Cancer in Postmenopausal WomenEnviron Health Perspect. 2022.