title: Genetic variation in BCL2 3'-UTR was associated with lung cancer risk and prognosis in male Chinese population.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors: 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.
authors: Ping
authors: P
authors: Xu
authors: Li
authors: L
authors: Liu
authors: Jianzhong
authors: J
authors: Wang
authors: Kai
authors: K
authors: Zhang
authors: Xiaohua
authors: X
authors: Hong
authors: Qifei
authors: Q
authors: Deng
authors: Jingjun
authors: J
authors: Xiang
authors: Xiaomin
authors: X
authors: Zhang
authors: Meian
authors: M
authors: He
authors: Tangchun
authors: T
authors: Wu
authors: Huan
authors: H
authors: Guo
mesh_terms: D020413:3' Untranslated Regions; D000368:Aged; D000483:Alleles; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D044466:Asian People; D002289:Carcinoma, Non-Small-Cell Lung / Q000208:ethnology / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D018628:Gene Dosage; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D012307:Risk Factors; D012907:Smoking; D016019:Survival Analysis
chemical_list: D020413:3' Untranslated Regions; D051017:Apoptosis Regulatory Proteins; D019253:Proto-Oncogene Proteins c-bcl-2
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