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- Title
Caspase 9 promoter polymorphisms and risk of primary lung cancer.
- Authors
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
- 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.
- Publication
Human Molecular Genetics, 2006, Vol 15, Issue 12, p1963
- ISSN
0964-6906
- Publication type
Article
- DOI
10.1093/hmg/ddl119