Zhao Hongguang, Chen Wenhu, Du Peng, Sun Aihua, Zhuang Chenyu, Tong Jiali, Wang Lifang
Department of Thoracic Surgery, Zhejiang Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology (Lung and Esophagus), Zhejiang Cancer Hospital, Hangzhou, 310022, People's Republic of China.
Tumour Biol. 2015 Jun;36(6):4319-26. doi: 10.1007/s13277-015-3071-5. Epub 2015 Jan 18.
Apoptosis is an important mechanism of malignant tumor formation and progression. Single nucleotide polymorphisms (SNPs) located within cell death genes may influence cancer risk. We explored the relationship between FasL -844T/C and/or Fas -1377G/A SNPs and pulmonary adenocarcinoma (AD). Two hundred seventy-five patients with pulmonary AD of South China admitted into Zhejiang Cancer Hospital from July 2007 to October 2011 were randomly selected, and their clinicopathological data were collected at the same time. Two hundred ninety-seven cases of healthy individuals were selected as control. FasL -844T/C and Fas -1377G/A SNPs were detected by PCR-RFLP technique to evaluate the relationships between these two SNPs and pulmonary AD. Age, FasL -844 and Fas -1377 SNPs were associated with increased risk of pulmonary AD susceptibility in main effect analysis. FasL -844CC and Fas -1377 AA were associated with an increased risk for the development of pulmonary AD only in age <60 years people, but not in those ≥60 years. FasL -844CC genotype was associated with an increased risk for pulmonary AD (adjusted OR = 2.010, 95 % CI 1.196-3.379, P = 0.008) compared with TT genotype. However, Fas -1377 AA was a risk factor only when FasL -844 genotype was CC. Fas -1377 genotypes showed significant effect modification of pulmonary AD risk by FasL -844 genotype with test of the interaction term adjusting for age, gender, and FasL -844 SNP. Fas -1377G/A was not associated with the clinicopathological factors, while FasL -844C/T was associated with tumor stage and lymph node metastasis in age ≥60 years people and tumor stage in those <60 years. In conclusion, FasL -844 SNP is associated with the susceptibility of pulmonary AD in age <60 years people. Fas -1377 SNP may modify the association of FasL -844 SNP with the risk of pulmonary AD. FasL -844 genotype plays an important role in the occurrence and progression of pulmonary AD.
细胞凋亡是恶性肿瘤形成和进展的重要机制。位于细胞死亡基因内的单核苷酸多态性（SNP）可能影响癌症风险。我们探讨了FasL -844T/C和/或Fas -1377G/A单核苷酸多态性与肺腺癌（AD）之间的关系。随机选取2007年7月至2011年10月入住浙江省肿瘤医院的275例华南地区肺腺癌患者，并同时收集其临床病理资料。选取297例健康个体作为对照。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）技术检测FasL -844T/C和Fas -1377G/A单核苷酸多态性，以评估这两种单核苷酸多态性与肺腺癌的关系。在主要效应分析中，年龄、FasL -844和Fas -1377单核苷酸多态性与肺腺癌易感性风险增加相关。FasL -844CC和Fas -1377 AA仅在年龄<60岁的人群中与肺腺癌发生风险增加相关，而在≥60岁的人群中则不然。与TT基因型相比，FasL -844CC基因型与肺腺癌风险增加相关（校正比值比=2.010，95%可信区间1.196-3.379，P=0.008）。然而，仅当FasL -844基因型为CC时，Fas -1377 AA才是一个危险因素。通过对年龄、性别和FasL -844单核苷酸多态性的交互项检验，Fas -1377基因型对肺腺癌风险有显著的效应修饰作用。Fas -1377G/A与临床病理因素无关，而FasL -844C/T在年龄≥60岁的人群中与肿瘤分期和淋巴结转移相关，在<60岁的人群中与肿瘤分期相关。总之，FasL -844单核苷酸多态性与年龄<60岁人群的肺腺癌易感性相关。Fas -1377单核苷酸多态性可能改变FasL -844单核苷酸多态性与肺腺癌风险的关联。FasL -844基因型在肺腺癌的发生和进展中起重要作用。
