Identification of polymorphisms in the Caspase-3 gene and their association with lung cancer risk

✍ Scribed by Jin Sung Jang; Kyung Mee Kim; Jin Eun Choi; Sung Ick Cha; Chang Ho Kim; Won Kee Lee; Sin Kam; Tae Hoon Jung; Jae Yong Park

• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: English
• Weight: 99 KB
• Volume: 47
• Category: Article
• ISSN: 0899-1987
• DOI: 10.1002/mc.20397

✦ Synopsis

Abstract

Caspase‐3 (CASP‐3) is a primary effector CASP that executes programmed cell death, and it plays an important role in the development and progression of cancer. Polymorphisms in the CASP‐3 gene may influence CASP‐3 production and/or activity, thereby modulating the susceptibility to lung cancer. To test this hypothesis, we first screened for polymorphisms in the CASP‐3 gene by direct sequencing of genomic DNA samples from 27 healthy Koreans, and then evaluated their associations with lung cancer in a case–control study that consisted of 582 lung cancer patients and 582 healthy controls. Individuals with at least one variant allele of the −928A > G, 77G > A, and 17532A > C polymorphisms were at a significantly decreased risk for lung cancer in comparison to the carriers with each homozygous wild‐type allele [adjusted odds ratio (OR) = 0.79, 95% confidence interval (CI) = 0.62–1.00, P = 0.05; adjusted OR = 0.78, 95% CI = 0.61–0.99, P = 0.04; and adjusted OR = 0.74, 95% CI = 0.58–0.95, P = 0.02, respectively]. Consistent with the results of genotyping analysis, the GAGC haplotype carrying the variant allele at all of the −928A > G, 77G > A, and 17532A > C loci was associated with a significantly decreased risk of lung cancer compared to the AGGA haplotype carrying no variant alleles at the three loci (adjusted OR = 0.66, 95% CI = 0.51–0.86, P = 0.002 and Bonferroni corrected P = 0.008). These results suggest that the CASP‐3 polymorphisms and their haplotypes contribute to the genetic susceptibility to lung cancer. © 2007 Wiley‐Liss, Inc.