BACKGROUND: Caspase7 (CASP7) is an executioner CASP that conducted a coordinated program of proteolysis that results in the destruction of critical cell structures, and it plays an important role in the development and progression of cancer. The purpose of this study is to comprehensively evaluate potential functional polymorphisms in the CASP7 gene in relation to the risk of lung cancer. METHODS: We first captured seven single nucleotide polymorphisms (SNPs) in the regulating region, exons and exon-intron boundaries of the CASP7 gene using public database and then determined their frequencies in 27 healthy Korean individuals. Next, we examined four SNPs (rs12415607g.C>A; rs11593766g.T>G; rs2227310g.C>G; and rs10787498g.T>C) in a case-control study that consisted of 720 lung cancer patients and 720 healthy controls. RESULTS: Of the four SNPs studied in the case-control study, only the distribution of the rs2227310g.C>G genotypes differed significantly between the cases and controls (P=0.03). The rs2227310 GG genotype was associated with a significantly increased risk of lung cancer when compared with the rs2227310 CC genotype [adjusted odds ratio (OR)=1.42, 95% confidence interval (CI)=1.05-1.93, P=0.02] and with the combined rs2227310 CC and CG genotype (adjusted OR=1.38, 95% CI=1.05-1.81, P=0.02). Consistent with the results of genotyping analysis, the ATGT haplotype (rs12415607A/rs11593766T/rs2227310G/rs10787498T) was associated with a significantly increased risk of lung cancer when compared to other haplotypes (adjusted OR=1.21, 95% CI=1.04-1.42, P=0.02). CONCLUSION: These results suggest that the CASP7 polymorphisms contribute to the genetic susceptibility to lung cancer.
BACKGROUND:Caspase7 (CASP7) is an executioner CASP that conducted a coordinated program of proteolysis that results in the destruction of critical cell structures, and it plays an important role in the development and progression of cancer. The purpose of this study is to comprehensively evaluate potential functional polymorphisms in the CASP7 gene in relation to the risk of lung cancer. METHODS: We first captured seven single nucleotide polymorphisms (SNPs) in the regulating region, exons and exon-intron boundaries of the CASP7 gene using public database and then determined their frequencies in 27 healthy Korean individuals. Next, we examined four SNPs (rs12415607g.C>A; rs11593766g.T>G; rs2227310g.C>G; and rs10787498g.T>C) in a case-control study that consisted of 720 lung cancerpatients and 720 healthy controls. RESULTS: Of the four SNPs studied in the case-control study, only the distribution of the rs2227310g.C>G genotypes differed significantly between the cases and controls (P=0.03). The rs2227310 GG genotype was associated with a significantly increased risk of lung cancer when compared with the rs2227310 CC genotype [adjusted odds ratio (OR)=1.42, 95% confidence interval (CI)=1.05-1.93, P=0.02] and with the combined rs2227310 CC and CG genotype (adjusted OR=1.38, 95% CI=1.05-1.81, P=0.02). Consistent with the results of genotyping analysis, the ATGT haplotype (rs12415607A/rs11593766T/rs2227310G/rs10787498T) was associated with a significantly increased risk of lung cancer when compared to other haplotypes (adjusted OR=1.21, 95% CI=1.04-1.42, P=0.02). CONCLUSION: These results suggest that the CASP7 polymorphisms contribute to the genetic susceptibility to lung cancer.
Authors: Chen-Yu Liu; Michael C Wu; Feng Chen; Monica Ter-Minassian; Kofi Asomaning; Rihong Zhai; Zhaoxi Wang; Li Su; Rebecca S Heist; Matthew H Kulke; Xihong Lin; Geoffrey Liu; David C Christiani Journal: Carcinogenesis Date: 2010-05-07 Impact factor: 4.944