Clotting Factor Gene Polymorphisms and Colorectal Cancer Risk

Abstract

PurposeIncreased coagulation has been associated with cancer onset and progression. Mainly small studies have addressed the association between clotting factor gene polymorphisms and the onset of colorectal cancer. We examined the association between six well-known clotting factor gene polymorphisms and colorectal cancer risk in a large case-control study.Patients and MethodsFactor V Leiden (rs6025), prothrombin G20210A (rs1799963), PAI-1 4G/5G (rs1799889), MTHFR 677C>T (rs1801133), fibrinogen gamma 10034C>T (rs2066865), and factor XIII Val34Leu (rs5985) were genotyped in 1,801 patients with colorectal cancer and 1,853 healthy controls from a large German population-based study. The risk of colorectal cancer associated with gene variants was determined by calculating odds ratios (ORs) and their 95% CIs using logistic regression.ResultsHomozygous carriers of the prothrombotic factor V Leiden polymorphism showed a 5.8-fold increased risk (95% CI, 1.69 to 19.72) for colorectal cancer compared with noncarriers. A 30% reduced risk was found for heterozygous carriers of factor V Leiden (OR = 0.68; 95% CI, 0.52 to 0.90) and prothrombin G20210A (OR = 0.69; 95% CI, 0.49 to 0.96), implying an advantage for slightly increased thrombin generation. Carriers of the antithrombotic factor XIII Val34Leu polymorphism showed a 15% reduced risk of developing colorectal cancer (OR = 0.85; 95% CI, 0.74 to 0.97) compared with noncarriers. Our results did not support an effect of PAI-1 4G/5G, MTHFR 677C>T, and fibrinogen gamma 10034C>T on colorectal cancer risk.ConclusionOur results support a role of clotting factor polymorphisms and thereby the coagulation system in the risk of colorectal cancer.