CASP3 polymorphisms and risk of squamous cell carcinoma of the head and neck

Purpose: Caspase-3 plays a central role in executing cell apoptosis and thus in carcinogenesis, but little is known about the role of CASP3 variants in susceptibility to SCCHN. Experimental Design: Genotype and haplotypes of the first intron (rs4647601:G>T and rs4647602:C>A) and 5′-untranslated region (UTR; rs4647603:G>A) of CASP3 (NT-022792.17) were determined for 930 SCCHN patients and 993 cancer-free controls in a U.S. non-Hispanic white population. Odds ratio (OR) and 95% confidence interval (95% CI) were calculated in multivariate logistic regression analysis. Results: We found that the CASP3 rs4647601:TT variant genotype was associated with an increased risk of SCCHN (adjusted OR, 1.32; 95% CI, 1.00-1.73) compared with the GG genotype. This risk was more evident in the subgroups of younger (≤56 years) subjects, males, and never smokers with a significant trend for increased risk with increased number of variant T allele (P < 0.05 for all). However, these risks were not found for other two SNPs. Furthermore, individuals with two copies of haplotypes TCG or GCA were found to have a significant increased risk of SCCHN (OR, 1.31; 95% CI, 1.07-1.61) compared with the other haplotypes, and this risk was more evident in less advanced diseases (OR, 1.45; 95% CI, 1.11-1.89) than in the advanced diseases (OR, 1.22; 95% CI, 0.96-1.54). Conclusions: These results suggested that genetic variation in CASP3 may contribute to SCCHN risk. Larger studies are needed to confirm our findings.