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The NOD2 3020insC Mutation and the Risk of Colorectal Cancer

Grzegorz Kurzawski¹, Janina Suchy¹, Józef Kadny², Ewa Grabowska³, Marek Mierzejewski¹, Anna Jakubowska¹, Tadeusz Dbniak¹, Cezary Cybulski¹, Elsbieta Kowalska¹, Zbigniew Szych⁴, Wenancjusz Domagaa⁵, Rodney J. Scott⁶ and Jan Lubiski¹

¹ International Hereditary Cancer Center, Department of Genetics and Pathology, Szczecin, Poland; Departments of ² General and Vascular Surgery, ⁴ Hygiene and Epidemiology, and ⁵ Pathology, Pomeranian Medical University, Szczecin, Poland; ³ Inter-University Unit of Molecular Biology, University of Szczecin and Pomeranian Academy of Medicine, Szczecin, Poland; and ⁶ Discipline of Medical Genetics, Faculty of Health, University of Newcastle, New South Wales, Australia

Several predispositions to colorectal cancer have been identified, but little is known about genetic susceptibilities to disease in older persons. Colorectal cancer is a risk in Crohn’s disease and is believed to be associated with an inappropriate inflammatory response. Recently, the NOD2 gene has been associated with Crohn’s disease, which further strengthens the notion that the inflammatory response plays a crucial role in this disease. Several mutations have been identified in the NOD2 gene, which appear with significantly higher frequency in patients with the disease. One such mutation (3020insC) is believed to be clearly causative because it results in a prematurely truncated protein with a predicted reduction in functional efficiency. In this report, we have examined the frequency of the 3020insC mutation in a series of 856 individuals including 556 patients with colorectal cancer. The frequency of the 3020insC mutation in a consecutive series of 250 non-hereditary nonpolyposis colorectal cancer patients >50 years of age was significantly elevated compared with the control population (odds ratio, 2.23; P = 0.0046). The results indicate that NOD2 may be a predisposing factor to colorectal cancer characterized by an older average age of disease onset in persons who do not harbor any other genetic predisposition to disease.

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