title: Common genetic variants in metabolism and detoxification pathways and the risk of papillary thyroid cancer.
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 P(trend) 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.
authors.affiliation: Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. brisa@uchicago.edu
authors.forename: Briseis
authors.initials: B
authors.lastname: Aschebrook-Kilfoy
authors.forename: Gila
authors.initials: G
authors.lastname: Neta
authors.forename: Alina V
authors.initials: AV
authors.lastname: Brenner
authors.forename: Amy
authors.initials: A
authors.lastname: Hutchinson
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Pfeiffer
authors.forename: Erich M
authors.initials: EM
authors.lastname: Sturgis
authors.forename: Li
authors.initials: L
authors.lastname: Xu
authors.forename: William
authors.initials: W
authors.lastname: Wheeler
authors.forename: Michele M
authors.initials: MM
authors.lastname: Doody
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Chanock
authors.forename: Alice J
authors.initials: AJ
authors.lastname: Sigurdson
mesh_terms: D000328:Adult; D000368:Aged; D000428:Alcohol Drinking / Q000235:genetics*; D002277:Carcinoma; D002291:Carcinoma, Papillary; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012907:Smoking / Q000235:genetics*; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism