Colorectal Cancer Risk and Ancestry in Colombian admixed Populations

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. 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. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was funded by European Union's Seventh Framework Programme under grant Agreement number 223678. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was approved by the committee of Bioethics of the University of Tolima and as well as the collaborating institutions: Hospital Federico Lleras Acosta, Hospital Pablo Tobon,Hospital San Vicente de Paul, Hospital Hernando Moncaleano Perdomo and Instituto Nacional de Cancerologia. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present work are contained in the manuscript