Fas/FasL genetic variants and risk for second primary maliganancy in patients with index oropharyngeal cancers versus index nonoropharyngeal head and neck cancers: A retrospective cohort study
Gene variants in the promoter region of the Fas/Fas ligand (FasLG) were considered in altering the transcriptional activity of those genes and consequently alter the regulation of cell death. However, the associations between the Fas/FasLG polymorphisms and risk for second primary malignancy (SPM) after index oropharyngeal cancer and index other non-oropharyngeal head and neck cancers were unknown. In this study Fas 670 A>G, Fas 1377 G>A, FasLG124 A>G, and FasLG 844C>T polymorphisms were genotyped in 752 patients with index SCCOP and 777 patients with index non-oropharyngeal SCCHN. Log-rank tests and cox proportional hazard models were used to assess the association with those four gene polymorphisms with SPM-free survival and SPM risk. Patients with index SCCOP and -844 CT/TT genotype had significantly less SPM-free estimate (log-rank P = 0.0448) and higher risk of SPM (HR, 2.74; 95% CI, 1.24-6.03) compared with -844 CC genotype. Patients with index non-oropharyngeal SCCHN and -670 AG/GGor -844 CT/TT genotypes had higher risks of SPM (HR, 2.39 and 1.73; 95% CI, 1.11-5.14 and 0.99-3.04, respectively). Carrying more Fas/FasL variant genes will significantly increase the risk of SPM among patients with index non-oropharyngeal SCCHN (P-trend = 0.0113). When stratified by different risk factors, only smoking status was found to modify the associations between Fas/FasL polymorphisms and risks for SPM among index oropharyngeal cancer patients. Age, ethnicity, smoking and drinking status, and index tumor stage were found to be potential effect modifier for the associations between Fas/FasL polymorphisms and risks for SPM. The results suggested Fas 670 A.G and FasLG 844C>T polymorphisms have significant effects on SPM-free survival among patients with index SCCOP and non-oropharyngeal SCCHN, respectively. Smoking along with the selected gene variants have modified the effects on the risk of SPM among both groups of patients, and other risk factors were found to have more effects among index non-oropharyngeal SCCHN patients. Further studies on specific index head and neck cancers can look closer on the associations between the Fas/FasLG gene variants and other non-oropharyngeal SCCHN.^
Biology, Biostatistics|Biology, Genetics|Health Sciences, Epidemiology
Jin, Anqi, "Fas/FasL genetic variants and risk for second primary maliganancy in patients with index oropharyngeal cancers versus index nonoropharyngeal head and neck cancers: A retrospective cohort study" (2014). Texas Medical Center Dissertations (via ProQuest). AAI3689772.