Polymorphisms of Death Pathway Genes FAS and FASL and Risk of Nasopharyngeal Carcinoma
Polymorphisms of Death Pathway Genes FAS and FASL and Risk of Nasopharyngeal Carcinoma
复制标题
DOI：
10.1002/mc.20676
复制
发表时间：
2010-11-01
影响因子：
4.6
通讯作者：
Shao, Jian-Yong
中科院分区：
文献类型：
--
作者：
Cao, Yun;Miao, Xiao-Ping;Shao, Jian-Yong
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. (C) 2010 Wiley-Liss, Inc.
