The nucleotide-binding oligomerization domain containing 2 (NOD2) gene is located on chromosome 16q21. It is expressed in monocytes, macrophages, epithelium of the digestive tract, breast, lung and in the kidney and is associated with the chronic inflammatory process and regulating apoptosis. A crucial role has been described in the maintenance of immune homeostasis and in the relationship with the microbiota. This gene has been linked to diseases such as Crohn's disease but also to gastric cancer, colon, endometrium, breast, ovary, bladder, lung or larynx. Our aim has been to estimate the association between polymorphism rs2066844 of the NOD2 gene on colon cancer by gender in a Mediterranean population.
We have carried out an observational study at baseline and longitudinally in the PREDIMED-Valencia study including 1094 participants (696 women) at high cardiovascular risk aged 67±6 years. We prospectively analyzed cancer incidence as a secondary outcome in this study. Lifestyle, clinical and biochemical variables were assessed by standardized methods. DNA was isolated from blood and the selected polymorphisms were determined.
We detected 21 new cases of colon cancer from 2003 to 2014, representing 1.9% of all cancers and 10% of all cancer cases in men and 11% in women respectively. In our study it was observed that the variant rs2066844 was related to the new cases of colon cancer in women but not in men. The allelic frequency of the T allele was 0.054, for which the carriers of the T allele were grouped in front of the CC carriers. When assessing the risk of having suffered colon cancer according to the genotype of this variant, it was observed that the individuals carrying the T allele presented a higher risk OR = 8.7: CI 95% (2.2-23.4); P = 0.002 after adjustment for sex, age, intervention group, tobacco smoking, alcohol drinking and intake of omega-3 fatty acids.
rs2066844 of the NOD2 gene could be associated with colon cancer in women in a high cardiovascular risk population.
Clinical trial identification
Legal entity responsible for the study
University of Valencia.
Instituto de Salud Carlos III.
All authors have declared no conflicts of interest.