Abstract 839: Interaction between solvent exposure and genetic susceptibility and risk for bladder cancer

Abstract Introduction: Recent studies have reported an increased bladder cancer risk with occupational exposure to organic solvents, including exposure to benzene, toluene, and xylene (BTX). The metabolism of solvents is known to be influenced by genetic susceptibility. Here, we evaluated the association between BTX and bladder cancer, stratified by genotype in known bladder cancer susceptibility loci and in variants shown to impact the metabolism of solvents. Methods: We evaluated if single-nucleotide polymorphisms (SNPs) modified the association between BTX exposure and bladder cancer risk in 1182 cases and 1408 controls from a population-based case-control study in New England. Ever and cumulative lifetime exposure to BTX was assessed using occupational histories obtained by personal interviews and exposure-oriented modules in conjunction with a job-exposure matrix. Genotyping was conducted using Illumina arrays and GSTM1 and GSTT1 deletion were determined using melt curve/copy number assays. We used multivariate logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between BTX exposure and bladder cancer, stratified by genotype and to calculate p-values for multiplicative interaction. Results: Ever exposure to BTX was more strongly associated with bladder cancer risk among individuals with the GSTT1 null (deletion) genotype (OR 3.53, 95% CI 1.26-9.89), while exposed individuals with the GSTT1 active genotype had a diminished risk (OR 1.40, 95% CI 0.93-2.10, P-interaction = 0.06). The association between benzene exposure and bladder cancer was similarly modified by GSTT1 genotype (carriers of the deletion: OR 5.19, 95% CI 1.91, 14.13; carriers of one or two copies: OR 1.22, 95% CI 0.79, 1.89, p-interaction=0.008). Conclusion: GSTT1 genotype has been shown to impair the metabolism of solvents, particularly for benzene. Here we show that bladder cancer risk is higher among those exposed to solvents who also harbor a common deletion in GSTT1, adding to the evidence of a plausible link between BTX exposures and bladder cancer risk. Citation Format: Deborah Tadesse, Nathaniel Rothman, Shuai Xie, Lauren Hurwitz, Melissa C. Friesen, Dalsu Baris, Molly Schwenn, Alison Johnson, Margaret Karagas, Debra T. Silverman, Stella Koutros. Interaction between solvent exposure and genetic susceptibility and risk for bladder cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 839.