Jang Jin Sung, Kim Kyung Mee, Choi Jin Eun, Cha Sung Ick, Kim Chang Ho, Lee Won Kee, Kam Sin, Jung Tae Hoon, Park Jae Yong
Department of Biochemistry, School of Medicine, Kyungpook National University, Daegu, Korea.
Mol Carcinog. 2008 May;47(5):383-90. doi: 10.1002/mc.20397.
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.
半胱天冬酶-3（CASP-3）是执行程序性细胞死亡的主要效应半胱天冬酶，它在癌症的发生和发展中起着重要作用。CASP-3基因的多态性可能会影响CASP-3的产生和/或活性，从而调节肺癌的易感性。为了验证这一假设，我们首先通过对27名健康韩国人的基因组DNA样本进行直接测序，筛查了CASP-3基因中的多态性，然后在一项病例对照研究中评估了它们与肺癌的关联，该研究包括582名肺癌患者和582名健康对照。与每个纯合野生型等位基因的携带者相比，具有-928A>G、77G>A和17532A>C多态性中至少一个变异等位基因的个体患肺癌的风险显著降低[调整后的优势比（OR）=0.79，95%置信区间（CI）=0.62-1.00，P=0.05；调整后的OR=0.78，95%CI=0.61-0.99，P=0.04；调整后的OR=0.74，95%CI=0.58-0.95，P=0.02]。与基因分型分析结果一致，在-928A>G、77G>A和17532A>C位点均携带变异等位基因的GAGC单倍型与在这三个位点均不携带变异等位基因的AGGA单倍型相比，患肺癌的风险显著降低（调整后的OR=0.66，95%CI=0.51-0.86，P=0.002，经Bonferroni校正后P=0.008）。这些结果表明，CASP-3多态性及其单倍型有助于肺癌的遗传易感性。
