부산대학교 도서관

Background: Several colorectal cancer susceptibility disease loci have been discovered through genome-wide association studies. However most of the variants were originally identified in Caucasian populations. Aim: To analyze the role of 20 known risk SNPs for colorectal cancer. Methods: Given that linkage disequilibrium is highly dependent on population demographic history and admixture background, we studied 20 risk SNPs in a pooled sample of 955 cases and 968 controls from admixed populations in Colombia. Results: The replication was reached for 11 out of 20 nominally associated SNPs; with allelic odds ratios (OR) ranging from 1.14 to 1.41, indicating a minimal increase in risk individually, however coinheritance of those SNPs resulted in an overall OR = 5.4 (95% CI: 3.052-9.731, P = 1.16E−08). Most of the variants followed a recessive model consistent with significant homozygous ORs distributed between 1.3 and 1.65. Among the most associated markers we found: 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). Conclusion: Our findings in Colombia have addressed the admixture and how this has influenced the risk associated with the known/unknown colorectal cancer regions, providing a comprehensive vision about several CRC-susceptibility SNPs identified in European populations, which also resulted, associated with an increased risk to CRC in the Colombian population, even though frequency and genetic structure differences accounted for those nonreplicated SNPs. [ABSTRACT FROM AUTHOR]