Polymorphisms in the survivin gene and the risk of lung cancer.
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.
Jang
Jin Sung
JS
Cancer Research Institute, Kyungpook National University School of Medicine, Daegu 700-422, Republic of Korea.
Kim
Kyung Mee
KM
Cancer Research Institute, Kyungpook National University School of Medicine, Daegu 700-422, Republic of Korea.
Kang
Kyung Hee
KH
Department of Internal Medicine, Kyungpook National University Hospital, Daegu 700-412, Republic of Korea.
Choi
Jin Eun
JE
Department of Biochemistry, Kyungpook National University School of Medicine, Daegu 700-422, Republic of Korea.
Lee
Won Kee
WK
Department of Preventive Medicine, Kyungpook National University School of Medicine, Daegu 700-422, Republic of Korea.
Kim
Chang Ho
CH
Department of Internal Medicine, Kyungpook National University Hospital, Daegu 700-412, Republic of Korea.
Kang
Young Mo
YM
Department of Internal Medicine, Kyungpook National University Hospital, Daegu 700-412, Republic of Korea.
Kam
Sin
S
Department of Preventive Medicine, Kyungpook National University School of Medicine, Daegu 700-422, Republic of Korea.
Kim
In-San
IS
Department of Biochemistry, Kyungpook National University School of Medicine, Daegu 700-422, Republic of Korea.
Jun
Jae Eun
JE
Department of Internal Medicine, Kyungpook National University Hospital, Daegu 700-412, Republic of Korea.
Jung
Tae Hoon
TH
Department of Internal Medicine, Kyungpook National University Hospital, Daegu 700-412, Republic of Korea.
Park
Jae Yong
JY
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.
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
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin