Research Article
Jamsheed Javid, Rashid Mir,
Abstract
Purpose: The study was conducted to determine the impact of promoter polymorphism in CASP9 gene on susceptibility and prognosis of Non Small Cell Lung Cancer patients of Indian origin. Patients and methods: Present case control study includes newly diagnosed 160 NSCLC patients and 160 healthy controls. Promoter polymorphism (-712C>T, rs4645981) in CASP9 gene was investigated using PCR-RFLP technique. Results: Our findings reveal that a statistically significant increased risk of about 2.6 fold was associated with homozygous TT genotype of CASP9 (-712C>T) promoter polymorphism (OR 4.3, 95%CI 2.2-8.3, p=0.0000) in Indian population .In addition smokers were at high risk for NSCLC which was more predominant in heavy smokers with pack-year >40 and in cigarette or beedi smokers. Compared to males, females were at high risk; about 2.3 fold more in association with homozygous TT genotype [OR, 3.9(1.9-8.2) in males vs. 6.2(1.4-27.1) in females]. Significant association was observed between advanced TNM stage (p<0.0001) and distant metastasis status (p<0.0001) of NSCLC patients with the polymorphism. Patients homozygous for T allele exhibited a significant poor overall survival compared with patients displaying CT+TT or CT or CC genotype (Median survival 6.0 vs. 9.0, 11.0, and 30.0, months respectively, p<0.0001). Also advanced stage patients with TT genotype showed lower median survival time than early stage NSCLC patients (Median 5.0 vs. 9.0 months respectively). Conclusion: The functional polymorphism (-712C>T) in the promoter region of CASP9 gene is associated with risk and susceptibility to NSCLC in north Indian population, and also is an important factor for poor prognosis in patients with NSCLC.