FAS and FASLG genetic variants and risk for second primary malignancy in patients with squamous cell carcinoma of the head and neck

Background: Single-nucleotide polymorphisms in the promoter region of the FAS and FASLG may alter the transcriptional activity of these genes. We therefore investigated the association between the FAS and FASLG polymorphisms and risk for second primary malignancy (SPM) after index squamous cell carcinoma of the head and neck (SCCHN). Methods: We used log-rank test and Cox proportional hazard models to assess the association of the four single-nucleotide polymorphisms (FAS -1377 G > A, FAS -670 A > G, FASLG -844 C > T, and FASLG -124 A > G) with the SPM-free survival and SPM risk among 1,286 incident SCCHN patients. Results: Compared with patients having the FAS -670 AA or the FASLG -844 CC genotypes, the patients having variant genotypes of FAS -670 AG/GG or FASLG -844 CT/TT genotypes had significantly increased risk for SPM, respectively. A trend for significantly increased SPM risk with increasing number of risk genotypes of the four polymorphisms was observed in a dose-response manner. Moreover, the patients with three or four combined risk genotypes had an ∼1.8- or 2.5-fold increased risk for developing SPM compared with patients with zero or one risk genotypes, respectively. Conclusions: Our results suggest a modestly increased risk for SPM after index SCCHN with FAS -670 A > G and FASLG -844 C > T polymorphisms and an even greater risk for SPM with multiple combined FAS and FASLG risk genotypes. Impact: The FAS and FASLG polymorphisms may serve as a susceptible marker for SCCHN patients at high SPM risk.