Association of Reduced Folate Carrier (RFC) Gene Polymorphism with Colorectal Cancer Susceptibility In Kashmir.

Folate, important cofactorin one carbon moiety transfer, has been a factor that may modulate the development of colorectal cancer through aberrant DNA methylation and altered nucleotide synthesis and repair. Major folate transport across cell membrane is mediated by reduced folate carrier-1 (RFC1) that also preferably transports chemotherapeutic agents. Variants within the RFC 1 by influencing folate uptake may lead to colorectal cancer susceptibility. Our study is the first to investigate prospectively the RFC gene polymorphism in colorectal cancer in Kashmiri population. A total of 620 subjects (300 colorectal cancer patients and 320 normal subjects) were analyzed by PCR-RFLP technique for RFC gene polymorphism in exon 2 at position 80. We observed 1.27 fold increased risk for AA homozygous variant (OR= 1.27; 95% CI, 0.8678 - 1.875) and 1.19 fold increased risk for GA heterozygous genotypes (OR= 1.19; 95% CI, 0.8080 - 1.760) respectively to CRC susceptibility. However the statistically significant results for smoking and tumor location characteristics were stratified with RFC1 polymorphism, which suggests a possible effect of smoking and cancer location in the etiology of CRC in Kashmir