Xu Ping, Liu Li, Wang Jianzhong, Zhang Kai, Hong Xiaohua, Deng Qifei, Xiang Jingjun, Zhang Xiaomin, He Meian, Wu Tangchun, Guo Huan
Department of Occupational and Environmental Health and Ministry of Education Key Lab for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
PLoS One. 2013 Aug 16;8(8):e72197. doi: 10.1371/journal.pone.0072197. eCollection 2013.
Bcl-2 is a critical apoptosis inhibitor with established carcinogenic potential, and can confer cancer cell resistance to therapeutic treatments by activating anti-apoptotic cellular defense. We hypothesized that genetic variants of BCL2 gene may be associated with lung cancer susceptibility and prognosis.
Three selected tagSNPs of BCL2 (rs2279115, rs1801018, and rs1564483) were genotyped in 1017 paired male Chinese lung cancer cases and controls by TaqMan assay. The associations of these variants with risk of lung cancer and overall survival of 242 male advanced non-small-cell lung cancer (NSCLC) patients were separately investigated.
Compared with the BCL2 3'UTR rs1564483GG genotype, the rs1564483GA, AA, and GA+AA genotypes were associated with significantly decreased susceptibilities of lung cancer in male Chinese (adjusted OR = 0.78, 0.73, and 0.76, P = 0.016, 0.038, and 0.007, respectively), while rs1564483A allele has a inverse dose-response relationship with lung cancer risk (P trend = 0.010). These effects were more evident in the elders, smokers, and subjects without family history of cancer (P trend = 0.017, 0.043 and 0.005, respectively). Furthermore, advanced NSCLC males carrying BCL2 rs1564483 GA+AA genotypes had significantly longer median survival time (Long-rank P = 0.036) and decreased death risk (adjusted HR = 0.69, P = 0.027) than patients with rs1564483GG genotype. These effects were more obvious in patients with smoking, stage IIIA, and in patients without surgery but underwent chemotherapy or radiotherapy (adjusted HR = 0.68, 0.49, 0.67, 0.69, 0.50, respectively, all P<0.05).
The BCL2 3'UTR rs1564483A allele was associated with a decreased lung cancer risk and better survival for advanced NSCLC in male Chinese, which may offer a novel biomarker for identifying high-risk population and predicting clinical outcomes.
Bcl-2是一种关键的凋亡抑制因子，具有明确的致癌潜能，可通过激活抗凋亡细胞防御机制使癌细胞对治疗产生抗性。我们推测BCL2基因的遗传变异可能与肺癌易感性和预后相关。
采用TaqMan分析法对1017对中国男性肺癌病例及对照中的3个选定的BCL2标签单核苷酸多态性（tagSNPs，rs2279115、rs1801018和rs1564483）进行基因分型。分别研究这些变异与肺癌风险以及242例男性晚期非小细胞肺癌（NSCLC）患者总生存期的关联。
与BCL2 3'UTR rs1564483GG基因型相比，rs1564483GA、AA以及GA + AA基因型与中国男性肺癌易感性显著降低相关（校正OR分别为0.78、0.73和0.76，P分别为0.016、0.038和0.007），而rs1564483A等位基因与肺癌风险呈反向剂量反应关系（P趋势 = 0.010）。这些效应在老年人、吸烟者以及无癌症家族史的受试者中更为明显（P趋势分别为0.017、0.043和0.005）。此外，携带BCL2 rs1564483 GA + AA基因型的晚期NSCLC男性患者的中位生存时间显著更长（对数秩检验P = 0.036），死亡风险降低（校正HR = 0.69，P = 0.027），优于rs1564483GG基因型患者。这些效应在吸烟患者、IIIA期患者以及未接受手术但接受化疗或放疗的患者中更为明显（校正HR分别为0.68、0.49、0.67、0.69、0.50，均P<0.05）。
BCL2 3'UTR rs1564483A等位基因与中国男性肺癌风险降低及晚期NSCLC更好的生存相关，这可能为识别高危人群和预测临床结局提供一种新的生物标志物。
