Abstract
Death receptor 4 (DR4) is a tumor suppressor gene and plays an important mediator of apoptosis. Polymorphism in DR4 gene may reduce apoptotic capacity and provoke proliferation of cell and cancer. We evaluated genetic polymorphisms of DR4 gene in association with risk of prostate cancer (PCa) in Northern Indian population. We have recruited 192 PCa patients and 225 cancer-free ages matched unrelated healthy control of similar ethnicity. They were genotyped for DR4, 141 (G>A), 209 (C>G), and 228 (A>C) polymorphisms using amplification refractory mutation system (ARMS) method. Variant genotype AA (OR=2.54; p=0.007) and A allele (OR=1.51; p=0.015) of DR4 141 demonstrated significant increased risk for PCa. Similarly, variant genotype GG (OR=2.58; p=0.003) and G allele carrier (CG+GG) (OR=1.50; p=0.043) of DR4 209 conferred increased risk. G allele (OR=1.50, p=0.005) was also statistically associated with PCa risk. High risk for PCa was also observed with respect to haplotypes A-G-A (OR=2.86; Bonferroni correction Pc=0.008) and A-G-C (OR=3.18, Pc=0.008). We observed significantly enhanced risk for PCa due to interaction between DR4 209 and 228 gene polymorphisms. Furthermore, a significantly increased risk of high Gleason grade tumor was found in the combined variant allele carrier (GA+AA) of DR4 141 compared with the GG genotype (OR=2.27, Pc=0.052). Interaction of smoking and genotypes did not further modulate the risk of PCa. Our observations suggested that genetic variants of the DR4 gene significantly influence the risk of PCa in North Indian population and might be involved in the etiology of PCa.