Jin Sung Jang1, Kyung Mee Kim1, Kyung Hee Kang2, Jin Eun Choi3, Won Kee Lee4, Chang Ho Kim2, Young Mo Kang2, Sin Kam4, In-San Kim3, Jae Eun Jun2, Tae Hoon Jung2, Jae Yong Park5. 1. Cancer Research Institute, Kyungpook National University School of Medicine, Daegu 700-422, Republic of Korea. 2. Department of Internal Medicine, Kyungpook National University Hospital, Daegu 700-412, Republic of Korea. 3. Department of Biochemistry, Kyungpook National University School of Medicine, Daegu 700-422, Republic of Korea. 4. Department of Preventive Medicine, Kyungpook National University School of Medicine, Daegu 700-422, Republic of Korea. 5. 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.
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.
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 cancerpatients 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.
Authors: Salvatore de Maria; Lorenzo Lo Muzio; Alessandra Braca; Paolo Rega; Amalia Cassano; Angela Vinella; Ruggiero Fumarulo; Rosario Serpico; Ernesto Farina; Vittoria Metafora; Giuseppe Pannone; Gian Pietro Ravagnan; Salvatore Metafora; Corrado Rubini; Maria Carteni; Maria Addolorata Mariggiò Journal: Oncol Lett Date: 2011-07-05 Impact factor: 2.967
Authors: Xiaoya Yang; Gang Xiong; Xuedan Chen; Xueqing Xu; Kai Wang; Yong Fu; Kang Yang; Yun Bai Journal: J Cancer Res Clin Oncol Date: 2009-04-08 Impact factor: 4.553