Common genetic variants in metabolism and detoxification pathways and the risk of papillary thyroid cancer

Briseis Aschebrook-Kilfoy, Gila Neta, Alina V. Brenner, Amy Hutchinson, Ruth M. Pfeiffer, Erich M. Sturgis, Li Xu, William Wheeler, Michele M. Doody, Stephen J. Chanock, Alice J. Sigurdson

Research output: Contribution to journalArticle

Abstract

Relationships are unclear between polymorphisms in genes involved in metabolism and detoxification of various chemicals and papillary thyroid cancer (PTC) risk as well as their potential modification by alcohol or tobacco intake. We evaluated associations between 1647 tagging single nucleotide polymorphisms (SNPs) in 132 candidate genes/regions involved in metabolism of exogenous and endogenous compounds (Phase I/II, oxidative stress, and metal binding pathways) and PTC risk in 344 PTC cases and 452 controls. For 15 selected regions and their respective SNPs, we also assessed interaction with alcohol and tobacco use. Logistic regression models were used to evaluate the main effect of SNPs (P trend) and interaction with alcohol/tobacco intake. Gene- and pathway-level associations and interactions (P gene interaction) were evaluated by combining Ptrend values using the adaptive rank-truncated product method. While we found associations between PTC risk and nine SNPs (P trend≤0.01) and seven genes/regions (P region<0.05), none remained significant after correction for the false discovery rate. We found a significant interaction between UGT2B7 and NAT1 genes and alcohol intake (P gene interaction=0.01 and 0.02 respectively) and between the CYP26B1 gene and tobacco intake (P gene interaction=0.02). Our results are suggestive of interaction between the genetic polymorphisms in several detoxification genes and alcohol or tobacco intake on risk of PTC. Larger studies with improved exposure assessment should address potential modification of PTC risk by alcohol and tobacco intake to confirm or refute our findings.

Original languageEnglish (US)
Pages (from-to)333-344
Number of pages12
JournalEndocrine-related cancer
Volume19
Issue number3
DOIs
StatePublished - Jun 2012

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Oncology
  • Endocrinology
  • Cancer Research

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    Aschebrook-Kilfoy, B., Neta, G., Brenner, A. V., Hutchinson, A., Pfeiffer, R. M., Sturgis, E. M., Xu, L., Wheeler, W., Doody, M. M., Chanock, S. J., & Sigurdson, A. J. (2012). Common genetic variants in metabolism and detoxification pathways and the risk of papillary thyroid cancer. Endocrine-related cancer, 19(3), 333-344. https://doi.org/10.1530/ERC-11-0372