Polymorphisms of FAS and FAS Ligand Genes Involved in the Death Pathway and Risk and Progression of Squamous Cell Carcinoma of the Head and Neck

Purpose: Alteration of the FAS/FAS ligand (FASLG) pathway regulating cell death may lead to cancer development, but the effects of functional promoter polymorphisms of the FAS and FASLG genes on risk of squamous cell carcinoma of the head and neck (SCCHN) are unknown. Design: We genotyped the FAS −1377 G>A, FAS −670 A>G, FASLG −844 C>T, and FASLG IVS2nt −124 A>G polymorphisms in 721 case patients with SCCHN and 1,234 cancer-free non–Hispanic White control subjects frequency-matched by age and sex. Multivariate logistic regression was used to assess the adjusted odds ratios (OR) and 95% confidence intervals (CI). Results: Compared with the FAS −1377 GG and −670 AA genotypes, the FAS −1377 AA and −670 (GG + AG) genotypes were associated with an increased risk of SCCHN (OR, 2.23; 95% CI, 1.07-4.64 and OR, 1.24; 95% CI, 1.01-1.52, respectively), whereas no risk of SCCHN was associated with any of the FASLG genotypes. When we used the combined FAS −1377 (GG + AG)/−670 AA genotypes as the reference, we found that the individuals carrying the FAS −1377 AA/−670 (GG + AG) had the highest risk (OR, 2.69; 95% CI, 1.24-5.83), whereas individuals carrying genotypes other than FAS −1377 (GG + AG)/−670 AA had a higher risk of SCCHN (OR, 1.24; 95% CI, 1.01-1.52). Furthermore, the elevated risk was particularly evident for pharyngeal cancer with the larger tumors without regional lymph metastasis (OR, 1.77; 95% CI, 1.07-2.94). Conclusions: The FAS (but not FASLG ) polymorphisms seem to contribute to risk of developing SCCHN, particularly the pharyngeal cancer in non–Hispanic Whites. However, potential selection bias warrants future population-based studies to verify the findings.