Polymorphisms of XPG/ERCC5 and risk of squamous cell carcinoma of the head and neck

Xeroderma pigmentosum group G (XPG) protein is essential for the nucleotide excision repair system, and genetic variations in XPG/ERCC5 that affect DNA repair capacity may contribute to the risk of tobacco-induced cancers, including squamous cell carcinoma of the head and neck (SCCHN). We investigated the association between XPG/ERCC5 polymorphisms and risk of SCCHN.

We genotyped 12 tagging and potentially functional single nucleotide polymorphisms (SNPs) of XPG/ERCC5 in a case-control study of 1059 non-Hispanic white patients with SCCHN and 1066 cancer-free age- and sex-matched controls, and evaluated their associations with the risk of SCCHN.

Multivariate logistic regression showed that only an intronic tagging SNP (rs4150351A/C) of XPG/ERCC5 was associated with a decreased risk of SCCHN (adjusted odds ratio=0.76, 95% confidence interval=0.62-0.92 for AC vs. AA; adjusted odds ratio=0.81, 95% confidence interval=0.67-0.98 for AC/CC vs. AA), but this association was nonsignificant after corrections by the permutation test (empirical P=0.105). In the genotype-phenotype correlation analysis using peripheral lymphocytes from 44 patients with SCCHN, we found that rs4150351 AC/CC was associated with a statistically significant increase in the XPG/ERCC5 mRNA expression.

These findings suggest that genetic variation in XPG/ERCC5 may not affect the risk of SCCHN, although rs4150351 C variant genotypes were associated with an increased expression of XPG/ERCC5 mRNA and nonsignificantly decreased risk of SCCHN. Larger population-based and additional functional studies are warranted to validate our findings.