Abstract B8: Sex-specific association between IL-1B-511 polymorphism and colorectal cancer in Colombian populations

Abstract

Abstract Background: In Colombia, colorectal cancer (CRC) has the fastest raising mortality rates. Carcinogenesis is related to chronic inflammation and single nucleotide polymorphisms (SNPs) in cytokines can affect gene expression, causing an effect in the degree of inflammation and carcinogenesis. IL-1 cytokine have a proinflammatory and carcinogenic effect. IL-1 B511C/TSNP has been related with gastric, breast, lung, cervical and colorectal cancer; however, results are not consistent among populations. Research supports the importance of inflammation in CRC, but few publications have explored its association with IL-1B polymorphisms. Aim: To evaluate the association of CRC and adenomatous polyps (AP) with IL-1 B-511 polymorphism in Colombian populations. Methods: We genotyped 324 invasive CRC cases and 206 low grade AP and 397 age-sex matched controls from a multicenter hospital-based case-control study, aimed to identify environmental and genetic risk factors for CRC in Colombian populations. All cases had incident diagnosis of CRC or AP, confirmed by histopathology. Controls that expressed no gastrointestinal symptoms were recruited at outpatient services from primary care units. Age ranged from 30 to 75 years old, subjects were unrelated and neither cases nor controls had personal history of other cancers. All the subjects gave informed consent to participate in this study, which includes answering guided-questionnaires (demographic, environmental and dietary factors) and blood collection. The study was approved by the ethical committee of the Instituto Nacional de Cancerologia. All the patients were genotyped for the IL-1B-517C/TSNP by TaqMan. Controls of known genotype for this SNP and negative controls were used. TaqMan analyses were repeated for 26% of the samples with 100% correlation. Hardy-Weinberg equilibrium was assessed in the control group for male and female separately. Statistical analysis was done by means of conditional logistic regression adjusting for potential confounding variables (familiar history of cancer, concomitant chronic diseases, smoking, NSAID and aspirin consumption, and place of origin). Recessive and codominant models were explored for genotype analysis. All analyses were run in STATA v11.0 Results: Control group was in Hardy-Weinberg equilibrium; allele frequencies in control men and women were the same (C, 0.45; T, 0.55) and were not significantly different from invasive cancer subjects (C, 0.45; T, 0.55) or adenomatous polyps subjects (C, 0.50; T, 0.50). After controlling for confounding factors, no association was observed between IL-1 B-511 polymorphism genotypes neither with polyps nor with invasive CRC. When analyzing separately by sex and specific site (right/left sided colon and rectum), higher risk of right-sided colon cancer was found only in male carriers with −511 C/T or T/T genotypes (OR 2.34; 95% Cl 1.42–3.87; p<0.005). No association was observed in cancer or polyps from the left sided colon or rectum in males and females. Conclusions: IL-1B-511 is associated with right-sided colon cancer in males supporting the general notion of different carcinogenic pathways involved in the origin of left and right-sided CRC in humans. Our results warrant further analyses to help understand the role of these and other related genetic variants in CRC or AP risk in Colombian population. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr B8.