Polymorphisms in the survivin gene and the risk of lung cancer

Jin Sung Jang, Kyung Mee Kim, Kyung Hee Kang, Jin Eun Choi, Won Kee Lee, Chang Ho Kim, Young Mo Kang, Sin Kam, In-San Kim, Jae Eun Jun, Tae Hoon Jung, Jae Yong Park

Research output: Contribution to journalArticle

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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. Conclusion: These results suggest that the survivin -31C > G polymorphism influences survivin expression, thus contributing to the genetic susceptibility to lung cancer.

Original languageEnglish
Pages (from-to)31-39
Number of pages9
JournalLung Cancer
Volume60
Issue number1
DOIs
Publication statusPublished - 2008 Apr 1
Externally publishedYes

Fingerprint

Single Nucleotide Polymorphism
Lung Neoplasms
Alleles
Genes
Odds Ratio
Confidence Intervals
Haplotypes
Adenocarcinoma
Genotype
Linkage Disequilibrium
Genetic Predisposition to Disease
DNA Sequence Analysis
Neoplasms
Histology
Apoptosis
Population

Keywords

  • Lung cancer
  • Polymorphism
  • Survivin
  • Susceptibility

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

Cite this

Jang, J. S., Kim, K. M., Kang, K. H., Choi, J. E., Lee, W. K., Kim, C. H., ... Park, J. Y. (2008). Polymorphisms in the survivin gene and the risk of lung cancer. Lung Cancer, 60(1), 31-39. https://doi.org/10.1016/j.lungcan.2007.09.008

Polymorphisms in the survivin gene and the risk of lung cancer. / Jang, Jin Sung; Kim, Kyung Mee; Kang, Kyung Hee; Choi, Jin Eun; Lee, Won Kee; Kim, Chang Ho; Kang, Young Mo; Kam, Sin; Kim, In-San; Jun, Jae Eun; Jung, Tae Hoon; Park, Jae Yong.

In: Lung Cancer, Vol. 60, No. 1, 01.04.2008, p. 31-39.

Research output: Contribution to journalArticle

Jang, JS, Kim, KM, Kang, KH, Choi, JE, Lee, WK, Kim, CH, Kang, YM, Kam, S, Kim, I-S, Jun, JE, Jung, TH & Park, JY 2008, 'Polymorphisms in the survivin gene and the risk of lung cancer', Lung Cancer, vol. 60, no. 1, pp. 31-39. https://doi.org/10.1016/j.lungcan.2007.09.008
Jang JS, Kim KM, Kang KH, Choi JE, Lee WK, Kim CH et al. Polymorphisms in the survivin gene and the risk of lung cancer. Lung Cancer. 2008 Apr 1;60(1):31-39. https://doi.org/10.1016/j.lungcan.2007.09.008
Jang, Jin Sung ; Kim, Kyung Mee ; Kang, Kyung Hee ; Choi, Jin Eun ; Lee, Won Kee ; Kim, Chang Ho ; Kang, Young Mo ; Kam, Sin ; Kim, In-San ; Jun, Jae Eun ; Jung, Tae Hoon ; Park, Jae Yong. / Polymorphisms in the survivin gene and the risk of lung cancer. In: Lung Cancer. 2008 ; Vol. 60, No. 1. pp. 31-39.
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AU - Jang, Jin Sung

AU - Kim, Kyung Mee

AU - Kang, Kyung Hee

AU - Choi, Jin Eun

AU - Lee, Won Kee

AU - Kim, Chang Ho

AU - Kang, Young Mo

AU - Kam, Sin

AU - Kim, In-San

AU - Jun, Jae Eun

AU - Jung, Tae Hoon

AU - Park, Jae Yong

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N2 - 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. Conclusion: These results suggest that the survivin -31C > G polymorphism influences survivin expression, thus contributing to the genetic susceptibility to lung cancer.

AB - 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. Conclusion: These results suggest that the survivin -31C > G polymorphism influences survivin expression, thus contributing to the genetic susceptibility to lung cancer.

KW - Lung cancer

KW - Polymorphism

KW - Survivin

KW - Susceptibility

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