Disinfection By-Products in Drinking Water and Bladder Cancer: Evaluation of Risk Modification by Common Genetic...

Area of Science:

• Environmental health
• Epidemiology
• Genetics

Background:

• Disinfection by-products (DBPs), particularly trihalomethanes (THMs), form when disinfectants interact with organic matter in water.
• THMs are linked to increased bladder cancer risk, with established exposure-response associations.
• Limited research has explored gene-environment interactions for THMs and bladder cancer susceptibility variants.

Purpose of the Study:

• To investigate the combined effects of total THMs (TTHMs), known bladder cancer susceptibility variants, and candidate gene variants on bladder cancer risk.
• To identify specific genetic factors that may modify the relationship between TTHM exposure and bladder cancer.

Main Methods:

• Analysis of data from two large case-control studies: the New England Bladder Cancer Study and the Spanish Bladder Cancer Study.
• Logistic regression models were used to estimate odds ratios (ORs) and confidence intervals (CIs) for TTHMs and genetic variants, including interaction terms.
• Meta-analysis was employed to combine results from both studies.

Main Results:

• A significant multiplicative interaction was observed between TTHMs and the rs907611 genotype (located in the LSP1 region) in both studies and meta-analysis.
• Individuals with the rs907611-GG genotype exposed to the highest TTHM levels showed a significantly increased bladder cancer risk.
• No consistent evidence of interaction was found for other tested genetic variants.

Conclusions:

• Novel suggestive evidence indicates a multiplicative interaction between TTHMs and rs907611 genotypes, suggesting a gene-environment interaction in bladder cancer development.
• Ubiquitous exposure to THMs highlights the importance of this finding.
• Further research is warranted to replicate these findings and elucidate the underlying molecular mechanisms.