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. Mol. Carcinog. © 2010 Wiley‐Liss, Inc.