The Association between Cyclin D1 (CCND1) rs9344 AA Genotype and Increased Risk of Colorectal Cancer in An Iranian Population

Abstract

Background: Colorectal cancer (CRC) is a globally growing disease with a steady decrease in the age of incidence. Pathogenesis of this cancer stems from a complex interaction between environmental factors and genetic predisposition. Among genetic factors, high activity of cyclin D1 gene is prominent. A polymorphism (G870A) in exon 4 of cyclin D1 is responsible for a variant transcript with longer half-life and may culminate in uncontrollable cellular growth, thereby contributing to cancer development. Method: This case-control study evaluated the frequency of CCND1 G870A polymorphism and risk of sporadic CRC in an Iranian population. The study population comprised 50 CRC patients and 50 CRC-free controls selected on the basis of colonoscopy examination. For genotyping, we performed polymerase chain reaction - restriction fragment length polymorphism analysis (PCR-RFLP). Result: AA genotype frequencies compared to GA+GG genotype frequencies between cases and controls showed that AA genotype frequency in the case group was significantly higher than the control group (AA vs. GG + GA: OR - 2.25, 95 CI: 1.13-5.54, P=0.04). Allele A frequency was 57 in patients and 46 in healthy subjects. Statistical analysis showed that the odds ratio of carriers with allele A for risk of CRC was 1.55 more than G allele carriers (OR=1.55, 95 CI: 0.856-2.828). Moreover, physical activity in cases was significantly less than controls (P 0.001). We further observed that the subjects in the case group used fewer non-steroidal anti-inflammatory drugs compared to healthy controls (P=0.02). Analysis of body mass index (BMI) between cases and controls revealed that the average of BMI in cases was higher than the controls (P =0.04). Conclusion: Our results showed that individuals carrying the AA genotype ran a higher risk of developing CRC compared to GG genotype.