Polymorphisms of death pathway genes FAS and FASL and risk of nasopharyngeal carcinoma.

The FAS receptor/ligand system is a key regulator of apoptotic cell death and corruption of this signaling pathway has been shown to participate in carcinogenesis. Functional polymorphisms in the FAS (FAS -1377G/A) and FASL (FASL -844T/C) genes alter their transcriptional activity. Therefore, we examined the association between these polymorphisms and the risk of developing nasopharyngeal carcinoma (NPC). FAS -1377G/A and FASL -844T/C genotypes were determined by PCR-based RFLP analysis in 582 patients with NPC and 613 frequency-matched controls. We observed a significantly increased risk of NPC associated with the FAS -1377AA genotype [odds ratio (OR) = 1.69, 95% confidence interval (CI) = 1.21-2.35] compared with the FAS -1377 GG genotype. In addition, elevated NPC risk was also found among subjects carrying both FAS -1377AA and FASL -844CC genotypes compared with both FAS -1377GG and FASL -844CT or -844TT, the OR was 2.39 (95% CI = 1.50-3.79). After stratification by smoking status, heavy smokers (≥15 pack-years) carrying FAS -1377AA genotype had an increased risk of NPC compared with FAS -1377GG genotype (OR = 3.48, 95% CI = 1.66-7.30). Furthermore, we observed a statistically significant interaction between the two polymorphisms and heavy smoking status (OR = 5.92, 95% CI = 1.91-18.3). Our study provides the first evidence that functional FAS -1377 G/A and FASL -844 T/C polymorphisms are associated with the risk of NPC, and this association is especially noteworthy in tobacco smokers.