title: Polymorphisms in the survivin gene and the risk of lung cancer.
abstract: BACKGROUND
  Survivin is an apoptosis inhibitor and plays an important role in the development and progression of cancer. Polymorphisms in the survivin gene may influence survivin production or activity, thereby modulating susceptibility to lung cancer. To test this hypothesis, we investigated the association between survivin polymorphisms and the risk of lung cancer in a Korean population.
  
  
  METHODS
  We first screened for polymorphisms in the survivin gene by direct sequencing of genomic DNA samples from 27 healthy Koreans. We selected identified SNPs based on their frequency, linkage disequilibrium status and haplotype tagging status, and then genotyped the selected SNPs in 582 lung cancer patients and 582 healthy controls who were frequency matched for age and gender.
  
  
  RESULTS
  We identified 8 single nucleotide polymorphisms (SNPs): 6 known SNPs [-644T>C, -625G>C, -31C>G, 9194A>G (K129E), 9386T>C and 9809T>C] and 2 novel SNPs (9974C>T and 10347G>A). Among the SNPs studied, only the -31C>G genotype distribution was significantly different between the cases and controls (P=0.04). Individuals with at least one -31G allele were at a significantly decreased risk of lung cancer compared to those individuals with the -31CC genotype [adjusted odds ratio (OR)=0.74, 95% confidence interval (CI)=0.57-0.96, P=0.02]. When the lung cancer cases were categorized by tumor histology, the -31G allele was associated with a significantly decreased risk of adenocarcinoma (adjusted OR=0.59, 95% CI=0.41-0.84, P=0.003). Consistent with the results of the genotyping analysis, the -625G/-31G/9194A/9809T haplotype carrying the -31G allele was associated with a significantly decreased risk of adenocarcinoma (adjusted OR=0.56, 95% CI=0.40-0.77, P=0.0004). The promoter assay revealed the -31G allele to have a significantly lower promoter activity than the -31C allele.
  
  
  CONCLUSIONS
  These results suggest that the survivin -31C>G polymorphism influences survivin expression, thus contributing to the genetic susceptibility to lung cancer.
authors.affiliation: Cancer Research Institute, Kyungpook National University School of Medicine, Daegu 700-422, Republic of Korea.
authors.forename: Jin Sung
authors.initials: JS
authors.lastname: Jang
authors.affiliation: Cancer Research Institute, Kyungpook National University School of Medicine, Daegu 700-422, Republic of Korea.
authors.forename: Kyung Mee
authors.initials: KM
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Kyungpook National University Hospital, Daegu 700-412, Republic of Korea.
authors.forename: Kyung Hee
authors.initials: KH
authors.lastname: Kang
authors.affiliation: Department of Biochemistry, Kyungpook National University School of Medicine, Daegu 700-422, Republic of Korea.
authors.forename: Jin Eun
authors.initials: JE
authors.lastname: Choi
authors.affiliation: Department of Preventive Medicine, Kyungpook National University School of Medicine, Daegu 700-422, Republic of Korea.
authors.forename: Won Kee
authors.initials: WK
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Kyungpook National University Hospital, Daegu 700-412, Republic of Korea.
authors.forename: Chang Ho
authors.initials: CH
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Kyungpook National University Hospital, Daegu 700-412, Republic of Korea.
authors.forename: Young Mo
authors.initials: YM
authors.lastname: Kang
authors.affiliation: Department of Preventive Medicine, Kyungpook National University School of Medicine, Daegu 700-422, Republic of Korea.
authors.forename: Sin
authors.initials: S
authors.lastname: Kam
authors.affiliation: Department of Biochemistry, Kyungpook National University School of Medicine, Daegu 700-422, Republic of Korea.
authors.forename: In-San
authors.initials: IS
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Kyungpook National University Hospital, Daegu 700-412, Republic of Korea.
authors.forename: Jae Eun
authors.initials: JE
authors.lastname: Jun
authors.affiliation: Department of Internal Medicine, Kyungpook National University Hospital, Daegu 700-412, Republic of Korea.
authors.forename: Tae Hoon
authors.initials: TH
authors.lastname: Jung
authors.affiliation: Department of Internal Medicine, Kyungpook National University Hospital, Daegu 700-412, Republic of Korea; Department of Biochemistry, Kyungpook National University School of Medicine, Daegu 700-422, Republic of Korea. Electronic address: jaeyong@kyungpook.ac.kr.
authors.forename: Jae Yong
authors.initials: JY
authors.lastname: Park
mesh_terms: D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008175:Lung Neoplasms / Q000209:etiology / Q000235:genetics*; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D000077022:Survivin
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin