Abstract 7368: Serum concentrations of per- and polyfluoroalkyl substances and mosaic loss of chromosome Y among men in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial
Authors: Jongeun Rhee, Vicky C. Chang, Weiyin Zhou, Mitchell J. Machiela, Jonathan N. Hofmann, Mark P. Purdue, Sonja I. Berndt
Journal: Cancer Research (2025)

Abstract Per- and polyfluoroalkyl substances (PFAS) are persistent organic pollutants detectable in the serum of most U.S. adults. Some PFAS are established or possible human carcinogens. Mechanistic studies in human cells and animals suggest PFAS may have genotoxic effects through indirect DNA damage caused by induction of oxidative stress or other mechanisms; however, evidence from human populations is limited. We investigated the relationship between serum PFAS concentrations and mosaic loss of chromosome Y (mLOY) as a biomarker of genotoxicity and genomic instability among men. We analyzed blood-derived DNA from 2, 377 men (aged 55-76 at blood collection) in three nested case-control studies within the PLCO Cancer Screening Trial. mLOY was detected using high-density genotyping array intensity data for chromosome Y. Pre-diagnostic serum concentrations of four PFAS [perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), perfluorononanoate (PFNA)] were measured. Using study-specific multivariable logistic regression, we estimated odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between serum PFAS and any detectable mLOY (overall mLOY) or mLOY affecting ≥10% of cells (expanded mLOY) among cases and cancer-free controls, separately. Results stratified by study and case-control status were summarized using a random-effects meta-analysis. Overall mLOY was detected in 22% of all men and 8.3% of all men had expanded mLOY. We found a suggestive positive association between serum PFHxS concentrations and mLOY (doubling in serum concentration, summary ORcontinuous=1.14, 95%CI=0.93-1.40; summary OR highest vs. lowest quartile=1.22, 95% CI=0.55, 2.69, P-trend=0.09). The magnitude of the association was stronger for those with a higher proportion of affected cells (expanded mLOY; doubling in serum concentration, ORcontinuous=1.19, 95% CI=0.89-1.59). No associations were observed with other PFAS. In conclusion, in this large population-based study, we observed suggestive evidence of a positive association between elevated serum PFHxS concentrations and mLOY. As the first study to evaluate PFAS in relation to mLOY, our findings, if confirmed, may provide new insight into PFHxS effects affecting genome maintenance, relevant for cancer development. Citation Format: Jongeun Rhee, Vicky C. Chang, Weiyin Zhou, Mitchell J. Machiela, Jonathan N. Hofmann, Mark P. Purdue, Sonja I. Berndt. Serum concentrations of per- and polyfluoroalkyl substances and mosaic loss of chromosome Y among men in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 7368.