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||COMMON GENETIC VARIANTS IN METABOLISM AND DETOXIFICATION PATHWAY GENES AND RISK OF PAPILLARY THYROID CANCER
||Schebrook-Kilfoy BA, Neta G, Brenner AV, Pfeiffer RM, Hutchinson AA, Sturgis EM, Xu L, Wheeler W, Ron E, Tucker MA, Chanock SJ, Sigurdson AJ
||AM J EPIDEMIOL
||2011 Jun 1
||BB, CGR, HGP, LTG, REB, OEEB
||Several enzymes are involved in the metabolism or detoxification of exogenous and endogenous agents and hormones, but few studies have addressed these processes in thyroid cancer risk. Genetic variation in these enzymes could affect the ability to mitigate effects of various environmental exposures or impact the rate of thyroid hormone conjugation. We evaluated the association between papillary thyroid cancer (PTC) and 1,750 single nucleotide polymorphisms (SNPs) in 128 candidate gene regions involved in exogenous xenobiotic and endogenous hormone metabolism, including phase I and II, oxidative stress, and metal binding pathways. In a case-control study of 344 PTC cases and 452 controls frequency matched on age and gender, we used unconditional logistic regression models to calculate odds ratios and p-values for log-additive trends with genotype. Gene region- and pathway-level associations were evaluated using combinations of SNP trend p-values with the adaptive rank truncated product method. We found evidence of an altered risk for PTC for 40 SNPs with p-values 0.05. Seven gene regions had p-values of < 0.05 (SOD1, CYP8B1, UGT2B7, MTF2, GSTT1, DHRS9, and FMO3). No significant associations at the pathway level were found. No SNPs or gene regions remained significant after correction for the false discovery rate. Our results suggest a role of some genetic variants in detoxification and hormone metabolizing enzymes in the etiology of PTC. Future studies should be conducted with greater power and by environmental exposure status to evaluate this hypothesis further.