Caspase 9 promoter polymorphisms and risk of primary lung cancer

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

Research output: Contribution to journalArticle

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Abstract

Caspase-9 (CASP-9) is an initiator CASP in the apoptosome-driven apoptosis pathway and plays an important role in the development and progression of cancer. Polymorphisms in the promoter region of the CASP-9 gene may influence the promoter activity of this gene, thereby modulating susceptibility to lung cancer. To test this hypothesis, we examined the association of four polymorphisms [-1263A>G, -905T>G, -712C>T and -293-275delCGTGAGGTCAGTGCGGGGA (-293del)] in the CASP-9 promoter with the risk of lung cancer in a Korean population. The CASP-9 genotypes were determined in 432 lung cancer patients and 432 healthy controls that were frequency-matched for age and gender. The -1263 GG genotype was associated with a significantly decreased risk of lung cancer compared with the -1263 AA genotype or combined -1263 AA + AG genotype [adjusted odds ratio (OR) = 0.64, 95% confidence interval (95% CI) = 0.42-0.98, P = 0.04 and adjusted OR = 0.67, 95% CI = 0.46-0.97, P = 0.01, respectively]. For the -712C>T polymorphism, individuals with at least one -712T allele were at a significantly increased risk of lung cancer compared with those harboring the -712 CC genotype (adjusted OR = 1.42, 95% CI = 1.06-1.89, P = 0.02). Consistent with the results of genotype analyses, the -1263G/-712C (G-C) haplotype was associated with a significantly decreased risk of lung cancer [adjusted OR = 0.59, 95% CI = 0.47-0.75, P and Bonferroni corrected P (Pc) < 0.001]. Moreover, the risk of lung cancer decreased in a dose-dependent manner as the number of the G-C haplotypes increased (adjusted OR = 0.60, 95% CI = 0.45-0.81, P = 0.0007 and Pc = 0.0014 for the G-C heterozygotes and adjusted OR = 0.34, 95% CI = 0.17-0.68, P = 0.0023 and Pc = 0.0046 for the G-C homozygotes; Ptrend < 0.001). The promoter assay revealed the G-C haplotype to have a significantly higher promoter activity than the -1263G/-712T and -1263A/ -712C haplotypes. These results suggest that CASP-9 promoter polymorphisms affect CASP-9 expression and contribute to genetic susceptibility to lung cancer.

Original languageEnglish
Pages (from-to)1963-1971
Number of pages9
JournalHuman Molecular Genetics
Volume15
Issue number12
DOIs
Publication statusPublished - 2006 Jun 15
Externally publishedYes

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Caspase 9
Lung Neoplasms
Odds Ratio
Genotype
Confidence Intervals
Haplotypes
Apoptosomes
Homozygote
Genetic Predisposition to Disease
Heterozygote
Genetic Promoter Regions
Genes
Alleles
Apoptosis

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Park, J. Y., Park, J. M., Jang, J. S., Choi, J. E., Kim, K. M., Cha, S. I., ... Jung, T. H. (2006). Caspase 9 promoter polymorphisms and risk of primary lung cancer. Human Molecular Genetics, 15(12), 1963-1971. https://doi.org/10.1093/hmg/ddl119

Caspase 9 promoter polymorphisms and risk of primary lung cancer. / Park, Jae Yong; Park, Jung Min; Jang, Jin Sung; Choi, Jin Eun; Kim, Kyung Mee; Cha, Sung Ick; Kim, Chang Ho; Kang, Young Mo; Lee, Won Kee; Kam, Sin; Park, Rang Woon; Kim, In-San; Lee, Jae Tae; Jung, Tae Hoon.

In: Human Molecular Genetics, Vol. 15, No. 12, 15.06.2006, p. 1963-1971.

Research output: Contribution to journalArticle

Park, JY, Park, JM, Jang, JS, Choi, JE, Kim, KM, Cha, SI, Kim, CH, Kang, YM, Lee, WK, Kam, S, Park, RW, Kim, I-S, Lee, JT & Jung, TH 2006, 'Caspase 9 promoter polymorphisms and risk of primary lung cancer', Human Molecular Genetics, vol. 15, no. 12, pp. 1963-1971. https://doi.org/10.1093/hmg/ddl119
Park JY, Park JM, Jang JS, Choi JE, Kim KM, Cha SI et al. Caspase 9 promoter polymorphisms and risk of primary lung cancer. Human Molecular Genetics. 2006 Jun 15;15(12):1963-1971. https://doi.org/10.1093/hmg/ddl119
Park, Jae Yong ; Park, Jung Min ; Jang, Jin Sung ; Choi, Jin Eun ; Kim, Kyung Mee ; Cha, Sung Ick ; Kim, Chang Ho ; Kang, Young Mo ; Lee, Won Kee ; Kam, Sin ; Park, Rang Woon ; Kim, In-San ; Lee, Jae Tae ; Jung, Tae Hoon. / Caspase 9 promoter polymorphisms and risk of primary lung cancer. In: Human Molecular Genetics. 2006 ; Vol. 15, No. 12. pp. 1963-1971.
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AU - Park, Jung Min

AU - Jang, Jin Sung

AU - Choi, Jin Eun

AU - Kim, Kyung Mee

AU - Cha, Sung Ick

AU - Kim, Chang Ho

AU - Kang, Young Mo

AU - Lee, Won Kee

AU - Kam, Sin

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N2 - Caspase-9 (CASP-9) is an initiator CASP in the apoptosome-driven apoptosis pathway and plays an important role in the development and progression of cancer. Polymorphisms in the promoter region of the CASP-9 gene may influence the promoter activity of this gene, thereby modulating susceptibility to lung cancer. To test this hypothesis, we examined the association of four polymorphisms [-1263A>G, -905T>G, -712C>T and -293-275delCGTGAGGTCAGTGCGGGGA (-293del)] in the CASP-9 promoter with the risk of lung cancer in a Korean population. The CASP-9 genotypes were determined in 432 lung cancer patients and 432 healthy controls that were frequency-matched for age and gender. The -1263 GG genotype was associated with a significantly decreased risk of lung cancer compared with the -1263 AA genotype or combined -1263 AA + AG genotype [adjusted odds ratio (OR) = 0.64, 95% confidence interval (95% CI) = 0.42-0.98, P = 0.04 and adjusted OR = 0.67, 95% CI = 0.46-0.97, P = 0.01, respectively]. For the -712C>T polymorphism, individuals with at least one -712T allele were at a significantly increased risk of lung cancer compared with those harboring the -712 CC genotype (adjusted OR = 1.42, 95% CI = 1.06-1.89, P = 0.02). Consistent with the results of genotype analyses, the -1263G/-712C (G-C) haplotype was associated with a significantly decreased risk of lung cancer [adjusted OR = 0.59, 95% CI = 0.47-0.75, P and Bonferroni corrected P (Pc) < 0.001]. Moreover, the risk of lung cancer decreased in a dose-dependent manner as the number of the G-C haplotypes increased (adjusted OR = 0.60, 95% CI = 0.45-0.81, P = 0.0007 and Pc = 0.0014 for the G-C heterozygotes and adjusted OR = 0.34, 95% CI = 0.17-0.68, P = 0.0023 and Pc = 0.0046 for the G-C homozygotes; Ptrend < 0.001). The promoter assay revealed the G-C haplotype to have a significantly higher promoter activity than the -1263G/-712T and -1263A/ -712C haplotypes. These results suggest that CASP-9 promoter polymorphisms affect CASP-9 expression and contribute to genetic susceptibility to lung cancer.

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