Jamsheed Javid, Rashid Mir, Masroor M, Shazia Farooq, Imtiyaz Ahamad, Mariyam Zuberi, Prasant Yadav, AA Bhat, Ishfaq Ah Sheikh, Tanveer Ah Khatlani, Julka PK, Anant Mohan, Maqbool Lone, Ray PC and Alpana Saxena
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.
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