Gene-environment interactions of novel variants associated with head and neck cancer

Background A genome-wide association study for upper aerodigestive tract cancers identified 19 candidate single-nucleotide polymorphisms (SNPs). We used these SNPs to investigate the potential genegene and geneenvironment interactions in head and neck squamous cell carcinoma (HNSCC) risk. Methods The 19 variants were genotyped using Taqman assays among 575 cases and 676 controls in our population-based casecontrol study. Results A restricted cubic spline model suggested both ADH1B and HEL308 modified the association between smoking pack-years and HNSCC. Classification and regression tree analysis demonstrated a higher-order interaction between smoking status, ADH1B, FLJ13089, and FLJ35784 in HNSCC risk. Compared with ever smokers carrying ADH1B T/C+T/T genotypes, smokers carrying ADH1B C/C genotype and FLJ13089 A/G+A/A genotypes had the highest risk of HNSCC (odds ratio = 1.84). Conclusions Our results suggest that the risk associated with these variants may be specifically important among specific exposure groups. (c) 2011 Wiley Periodicals, Inc. Head Neck, 2012