Abstract
Background: Chronic inflammation is a vital component of colorectal cancer pathogenesis. Interleukin-1 beta (IL-1 beta) is one of the key regulators of GIT inflammatory homeostasis and plays a vital role in several pathophysiological processes in the GIT including inflammatory bowel diseases (IBDs) (Crohn's disease and ulcerative colitis) that are associated with an increased risk of CRC. Several studies have reported the association of IL1 beta-31C/T and IL1 beta-511T/C single nucleotide polymorphisms (SNPs) in human IL-1 beta gene with various cancers including colorectal cancer but the association of these SNPs with CRC risk in Kashmiri population is yet to be studied.
Materials and methods: The aim of this study was to analyze the association of IL1 beta-31C/T and IL1 beta-511T/C promoter SNPs with colorectal cancer (CRC) risk in ethnic Kashmiri population through a case-control study. The genotype frequencies of IL1 beta-31C/T and IL1 beta-511T/C promoter SNPs were analyzed in 142 CRC patients and 184 individually matched healthy controls by using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method. The conditional logistic regressionmodels adjusted for multiple possible confounding (third) variableswere used to study the association between the IL1 beta-31C/T and IL1 beta-511T/C SNPs and CRC risk. The effect modification of the association between the relevant SNP genotypes and CRC risk by various CRC risk factors including age, gender and smoking status was also evaluated. Further, the associations between various clinico-pathological parameters, demographic variables and environmental factors within the case group subjects and the SNPs under study in relation to CRC risk were also analyzed.
Results: The overall association between the IL1 beta-31C/T and IL1 beta-511T/C SNPs and the modulation of CRC risk was not found to be significant (p value = 0.839 and p value = 0.054 respectively). Further, we found no significant effect modification of CRC risk by relevant IL1 beta-31C/T and IL1 beta-511T/C SNP genotypes in presence of different possible risk factors (p > 0.05). We found no significant association between the IL1 beta-31C/T promoter SNP with the subsets of various characteristics of the case group subjects (p > 0.05) but IL1 beta-511 T/C SNP was significantly associated with dwelling (p = 0.0419), tumor grade (p = 0.028) and lymph node status (p = 0.049).
Conclusion: This study has demonstrated that the association between the IL1 beta-31C/T and IL1 beta-511T/C promoter SNPs and risk of CRC in ethnic Kashmiri population is not significant. However, replicating this study with larger sample size and with other ethnically defined populations with comparable CRC incidence may substantiate and elaborate our findings in a more comprehensive manner. (c) 2017 Elsevier B.V. All rights reserved.