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Introduction: Colorectal cancer (CRC) heritability is determined by the composite relations between inherited variants and environmental factors. In developing countries like India, the incidence rates of CRC are especially increasing. In this study, we have focused on the distribution of the FOXO3 gene polymorphisms among the patients with colorectal cancer in North India. Methods: A case–control study was conducted on 487 colorectal cancer patients and 487 age-matched controls. We genotyped SNPs rs2253310 and rs4946936 through PCR-Restriction fragment length polymorphism (RFLP) analysis and PCR-single stranded conformation polymorphism (SSCP) procedure followed by sequence detection. Results: A significantly increased risk of CRC was observed for the CC genotype of the rs4946936 polymorphism compared to the TT genotype (p= 0.02; OR= 1.40 CI=1.05-1.87). GT haplotype appeared to be a “risk” haplotype (OR- 1.71, 95%CI= 0.82~2.19), while as other haplotypes CC (OR- 0.83, 95% CI=0.32~1.54]), CT (OR- 0.75, 95%CI= 0.25~1.01) and GC (OR- 0.98, 95%CI= 0.88~1.14) were found to be “protective” for developing colorectal cancer. Conclusion: This study suggests an association of increased risk of CRC with the rs4946936 polymorphism, but not with the rs2253310 polymorphism.

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