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 gene-gene and gene-environment 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 case-control 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.