Population-Specific Genetic Variation of TRAIL in Ovarian Cancer

Objective: Genome-wide, high-throughput technologies have made major advances in understanding the molecular basis of ovarian cancer and contribution of a single genetic variant, multiple genetic variants, and the contribution of cumulative effect of a genetic variant and an environmental factor to the difference in the incidence of disease have been extensively studied. There is a progressive increase in the studies related to TRAIL mediated signaling and it has been reported that there is a highly polymorphic region in the TRAIL promoter with four SNPs located in a 111 base pair (bp) spanning sequence between nucleotides 707 and 597 upstream of the transcriptional start site. Methodology: A C/T polymorphism at 1595 position in exon 5 of the TRAIL gene was genotyped in a Pakistani Ovarian cancer case-control population including 19 cases and 24 controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Results: In the present study, we determined TRAIL 1595 C/T polymorphism in 19 ovarian cancer patients and 24 controls. The results indicated that out of 19 patients 10 (52.6%) were of CT genotype. 6 (31.5%) were homozygous for C and 3 (15.7%) were homozygous for T. Genotyping of age and sex matched controls revealed that out of 24, 9 (37.5%) were of CT genotype. 12 (50%) were CC and 3 (12.5%) were TT. Conclusion: TRAIL and Death Receptors are components of apoptotic signaling networks, and a better knowledge of how these networks operate is an important step in understanding cancer progression. Our research group is the first to report role of the TRAIL polymorphism at position 1595 in 3'UTR in ovarian cancer risk and progression.