Colorectal Cancer Risk and Ancestry in Colombian admixed Populations

Abstract

ABSTRACTSeveral colorectal cancer susceptibility disease loci have been discovered through Genome-wide association studies. However most of the variants were originally identified in Caucasian populations. Demographic history and admixture background may impact the association of known CRC variants due to the differences in linkage disequilibrium across different populations. We performed a genomic study in a sample of 955 cases and 968 controls from admixed populations in Colombia by genotyping ∼1 million SNPs aimed to detect the impact of genetic structure in the association of 20 known SNPs risk for colorectal cancer. The replication was reached for eleven out of 20 nominally associated SNPs; with allelic odds ratios (OR) between 1.14 and 1.41, indicating a minimal individual risk increment; on the other hand, the overall OR for co-inherited SNPs was 5.4 (95% CI: 3.052-9.731,P=1.16E-08). Most of the variants followed a recessive model with significant homozygous ORs distributed between 1.3 and 1.65. The major associated markers were: rs4939827 (18q21.1,P=7.35E-6), rs10411210 (19q13.11,P=0.001) rs10795668 (10p14,P=0.0024), rs4444235 (14q.2.2,P=0.005), rs961253 (20p12.3,P=0.006), rs16892766 (8q23.3,P=0.011) and rs1050547 (8q24.21,P=0.017). Additionally, European ancestral component was associated with colorectal cancer risk (p=6.48E-04, OR = 4.244 95% IC: 1.701-10.68). Our findings in Colombia indicates a significant contribution of the known CRC risk SNPs to the disease in the Colombian population, which in turns can be explained by the genetic European component influx during the admixture process. The unassociated SNPs indicates frequency and genetic structure differences between European and Colombian populations or due to the sample process.