Integrin alpha-2 and beta-3 gene polymorphisms and colorectal cancer risk

Background and aims  Integrins such as α₂β₁, α_IIbβ₃, and α_vβ₃ have been suggested as key players for cancer development and progression. Several polymorphisms affecting these molecules, two in integrin α₂ (ITGA2 807C>T and 1648G>A) and one in β₃ (ITGB3 176T>C), influence their levels, structure, and possibly their function. To analyze the role of ITGA2 and ITGB3 polymorphisms for colorectal cancer risk and clinical presentation, we performed a case–control study. Materials and methods  Four hundred thirty-three colorectal cancer patients and 433 healthy sex- and age-matched control subjects were investigated. ITGA2 and ITGB3 polymorphisms were determined by 5′-nuclease assays. Results/findings  The ITGA2 807C>T polymorphism was associated with reduced colorectal cancer risk. In a codominant model, the odds ratio for each additional 807-T allele for colorectal cancer was 0.77 (95% confidence interval 0.64–0.94; p = 0.011). The ITGA2 1648G> and the ITGB3 176T>C polymorphism were not associated with colorectal cancer. None of the three polymorphisms investigated was associated with tumor size, histological grade, presence of primary lymph node metastases, tumor stage, or age at diagnosis. Interpretation/conclusion  We conclude that the ITGA2 807C>T polymorphism may be associated with reduced colorectal cancer risk. Armin Gerger and Günter Hofmann contributed equally to this work.