Functional Role of CyclinD1 Polymorphism (G870A) in Modifying Susceptibility and Overall Survival of North Indian Lung Cancer Patients.

Abstract

Purpose The purpose of this study was to investigate the potential role of the cyclin D1 gene G870A polymorphism in the likelihood of the development of lung cancer and the overall survival of lung cancer patients in the North Indian population. Methods The study consisted of 353 lung cancer cases and 351 age- and gender-matched healthy controls. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLPP) was done for the CCND1 gene. The association analysis was done using the multiple linear regression, and the survival analysis was done using the Kaplan-Meier and the Cox regression models. Results The GA genotype was associated with an increased risk for overall lung cancer (odds ratio [OR] = 1.63; p = 0.01). Combined variant genotype showed a significant association for overall lung cancer (OR 1.50; p = 0.03). In addition, smokers with the carrier genotype of CCND1 were found to have a significantly higher risk for lung cancer (OR 1.57; p = 0.04). No significant correlation was observed between the overall survival of lung cancer patients and CCND1 polymorphism. However, on stratifying the subjects on the basis of histology, it was evident that small-cell lung cancer (SCLC) patients carrying the mutant (AA) genotype showed nearly a fivefold increased mortality rate compared to the wild (GG) genotype (p = 0.03). Conclusions Our results suggest that polymorphic CCND1 may increase the risk of lung cancer in smokers from North India, and it may be associated with the overall survival of SCLC patients.