title: Joint effects of alcohol consumption and polymorphisms in alcohol and oxidative stress metabolism genes on risk of head and neck cancer.
abstract: BACKGROUND
  Single-nucleotide polymorphisms (SNP) in alcohol metabolism genes are associated with squamous cell carcinoma of the head and neck (SCCHN) and may influence cancer risk in conjunction with alcohol. Genetic variation in the oxidative stress pathway may impact the carcinogenic effect of reactive oxygen species produced by ethanol metabolism. We hypothesized that alcohol interacts with these pathways to affect SCCHN incidence.
  
  
  METHODS
  Interview and genotyping data for 64 SNPs were obtained from 2,552 European- and African-American subjects (1,227 cases and 1,325 controls) from the Carolina Head and Neck Cancer Epidemiology Study, a population-based case-control study of SCCHN conducted in North Carolina from 2002 to 2006. We estimated ORs and 95% confidence intervals (CI) for SNPs and haplotypes, adjusting for age, sex, race, and duration of cigarette smoking. P values were adjusted for multiple testing using Bonferroni correction.
  
  
  RESULTS
  Two SNPs were associated with SCCHN risk: ADH1B rs1229984 A allele (OR = 0.7; 95% CI, 0.6-0.9) and ALDH2 rs2238151 C allele (OR = 1.2; 95% CI, 1.1-1.4). Three were associated with subsite tumors: ADH1B rs17028834 C allele (larynx, OR = 1.5; 95% CI, 1.1-2.0), SOD2 rs4342445 A allele (oral cavity, OR = 1.3; 95% CI, 1.1-1.6), and SOD2 rs5746134 T allele (hypopharynx, OR = 2.1; 95% CI, 1.2-3.7). Four SNPs in alcohol metabolism genes interacted additively with alcohol consumption: ALDH2 rs2238151, ADH1B rs1159918, ADH7 rs1154460, and CYP2E1 rs2249695. No alcohol interactions were found for oxidative stress SNPs.
  
  
  CONCLUSIONS
  Previously unreported associations of SNPs in ALDH2, CYP2E1, GPX2, SOD1, and SOD2 with SCCHN and subsite tumors provide evidence that alterations in alcohol and oxidative stress pathways influence SCCHN carcinogenesis and warrant further investigation.
authors.affiliation: Department of Epidemiology, University of North Carolina at Chapel Hill, 100 Market Street, Chapel Hill, NC 27516, USA. ahakenewerth@gmail.com
authors.forename: Anne M
authors.initials: AM
authors.lastname: Hakenewerth
authors.forename: Robert C
authors.initials: RC
authors.lastname: Millikan
authors.forename: Ivan
authors.initials: I
authors.lastname: Rusyn
authors.forename: Amy H
authors.initials: AH
authors.lastname: Herring
authors.forename: Kari E
authors.initials: KE
authors.lastname: North
authors.forename: Jill S
authors.initials: JS
authors.lastname: Barnholtz-Sloan
authors.forename: William F
authors.initials: WF
authors.lastname: Funkhouser
authors.forename: Mark C
authors.initials: MC
authors.lastname: Weissler
authors.forename: Andrew F
authors.initials: AF
authors.lastname: Olshan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000428:Alcohol Drinking / Q000453:epidemiology* / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology* / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006258:Head and Neck Neoplasms / Q000453:epidemiology* / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009657:North Carolina / Q000453:epidemiology; D018384:Oxidative Stress / Q000235:genetics*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D000077195:Squamous Cell Carcinoma of Head and Neck; D055815:Young Adult