Involvement of CASP3 promoter polymorphism (−1337 C > G) in the development and progression of non-small cell lung cancer

Abstract

Downregulation of CASP3 gene expression has been observed to be associated with various malignancies, and promoter polymorphisms in the CASP3 gene may have a great impact on the CASP3 transcriptional activity. The present study aimed to analyze the possible impact of the CASP3 (−1337 C > G, rs1405937) polymorphism on the expression profile of CASP3 gene and ultimately its association in the development of non-small cell lung cancer. A case–control study of 100 non-small cell lung cancer patients and 100 cancer free healthy controls was conducted, wherein genotype and expression profile of CASP3 gene were evaluated using serum DNA and serum RNA, respectively, by primer-introduced restriction fragment analysis and real-time PCR techniques. Compared to the CASP3 CC genotype, odds ratio of 11.1 was found to be associated to the homozygous GG genotype with more than sixfold decrease of CASP3 gene expression in non-small cell lung cancer patients. Significant trend of decrease in caspase 3 expression was observed with the increase in severity of the disease. Patients with CASP3 (−1337GG) genotype had significantly shorter overall survival compared to CASP3 (−1337CC) genotype carriers. In addition, significantly poor overall survival was also reflected by patients with higher fold decrease in CASP3 gene expression. CASP3 (−1337 GG) genotype was found to be associated with significantly lower CASP3 gene expression especially among patients with advanced status of the disease, suggesting that CASP3 (−1337C > G) polymorphism may be involved in the development and progression of non-small cell lung cancer.

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