Background: Colorectal cancer mortality rates are heterogeneous across Colombian territory and this variation could be explained by regional differences in Colombian ethnicity due to our high population admixture. Different frequencies of the interleukin 1 beta (IL1B) genetic variations have been described among diverse ethnical groups, but there are no reports on the possible association of these variants with colorectal cancer (CRC) risk as an effect of the genetic population dynamics in Colombia.

Methods: To evaluate the association of IL1B haplotypes with colorectal carcinogenesis, we genotyped 317 CRC cases, 199 adenomatous polyps (AP) and 511 age-sex matched controls recruited from six Colombian cities located either on the coastal or the inner zone of the country. Five IL1B SNPs (-3737, -1464, -511, -31 and +3954) were genotyped and all were in HWE (p>0.05). We used data from previous analysis to estimate individual ancestral genetic fractions using STRUCTURE software based on allele frequencies of 678 autosomal SNPs cross-matched with the HapMap dataset, not in LD, and assuming three distinct population origins (CEU, LWJ and CHB populations) from HapMap project as references.

Results: We found a 4-SNPs haplotype block (-3737C/-1464G/-511T/-31C) with high LD associated with CRC risk. Additional analysis revealed that this association persisted after adjusting by confounding variables including ancestry information (OR 1.95; CI 1.12 - 3.38; p =0.02). Interestingly, this association was evident among individuals from the coastal zone of the country and it was related with their higher African ancestry fraction (OR 2.26; 95%CI 1.22-4.18; p =0.01). Our results are in agreement with previous reports showing that this haplotype increase the IL1B promoter activity and that is highly prevalent in African-Americans.

Conclusions: To the best of our knowledge, this is the first study seeking for the association between CRC risk and IL1B gene in a haplotype context in a population-based association study in Colombia, an admixed population. Our results represent consistent evidence on how the identification of genetic biomarkers of susceptibility could be used to discriminate populations at increased risk of CRC development.

Citation Format: Maria Carolina Sanabria-Salas, Gustavo Hernandez-Suarez, Adriana Umaña-Perez, Martha Lucia Serrano-Lopez, Myriam Sanchez-Gomez, Martha Patricia Rojas, Jovanny Zabaleta. Colombians with high percentage of African ancestry, carrying a specific IL1B haplotype, have increased risk of colorectal cancer. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr B23. doi:10.1158/1538-7755.DISP13-B23

©2014 American Association for Cancer Research.
2014