In:
Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 25, No. 3_Supplement ( 2016-03-01), p. PR08-PR08
Abstract:
Background: Latin-Americans have different proportions of Amerindian, African and European genetic ancestry. Particularly, in Colombia the degree of admixture varies across the country as a result of very complex demographic events taken place since 16th century (colonization) and sex-bias gene flow effects. Colorectal cancer (CRC) mortality rates are heterogeneous across Colombian territory and this variation could be explained by regional differences in Colombian genetic background. Methods: To evaluate the association of genetic ancestry and colorectal adenomas and cancer risk, we genotyped 813 samples from Colombian coastal and andean regions, including 349 controls, 292 CRC cases and 172 adenomatous polyps (AP). Autosomal and X-chromosome individual ancestries were estimated using ADMIXTURE software with 556 AIMS (Fst & gt; 0.5 among HAPMAP reference populations; k=3) and differences in ancestry proportions were assessed using a t-test. Multinomial logit model analysis between phenotype and ancestry proportions (covariates: sex, age, NSAIDs consumption, city of provenance and educational level) were conducted in R. Results: We found statistical differences (p & lt; 0.05) between African, European and Asian (as a measure of Amerindian) ancestry means of autosomes versus X-chromosome (sex bias). As expected, ancestry means were different between the coast versus andean regions (African 0.27 vs 0.09; European 0.44 vs 0.57 and Asian/Amerindian 0.29 vs 0.35, respectively), reflecting differences among cities. For controls, AP and CRC the respective ancestry means were: African (0.17, 0.18 and 0,20), European (0.50, 0.53 and 0.48) and Asian/Ameridian (0.33, 0.29, 0.32). Univariate analysis showed that European ancestry was associated with an increased risk of AP (p & lt; 0.05) and that African ancestry was associated with an increased risk of CRC (p & lt; 0.05); no differences were found for phenotype among cities. After running full multinomial model, the association between European ancestry and the risk of AP remained (OR 8.50; 95%CI 1.65-43.78; p = 0.011); on the other hand, the association between African ancestry and CRC risk had the same direction but was not significant (OR 1.06; 95%CI 1.00-1.13, p = 0.065). On the full model, we also found that Colombians with no education have more CRC than those with at least high school degree, and this was consistent with univariate analysis. No differences were seeing between educational level and AP, neither in the univariate nor in the multivariate analysis, even though multinomial model of education by ancestry (corrected by city), showed that Colombians with high European ancestry are more likely to hold advance education degree. Conclusions: Colombian regions have differences in the degree of admixture as a consequence of the highly asymmetric pattern of mating of European men with Native American women and the African slavery trade in the coasts since the colonization period, according to this study and others on Y-chromosome and mtDNA. There was no signal of sampling bias in our study (no differences in phenotypes by city). The association of CRC risk and African ancestry did not remain in the full model, probably due to a small effect, small sample size or the fact that people without education (low socioeconomical status) have less access to health system. The association of AP risk with European ancestry remained after controlling with covariates (including educational level); this probably indicates that there are European genetic factors (ej: SNPs) modifying the risk of AP in Colombians. Our results highlight the importance of performing Local Admixture Inference analysis in order to estimate the ancestry of specific chromosomal regions in admixed individuals in the study of human evolutionary history and genetic association studies. This abstract is also presented as Poster C37. Citation Format: Maria Carolina Sanabria-Salas, Gustavo Adolfo Hernández-Suárez, Adriana Umaña-Pérez, Martha Lucía Serrano-Pérez, Myriam Sánchez de Gómez, Martha Patricia Rojas, Jovanny Zabaleta, Konrad Rawlik, Albert Tenesa. The role of genetic structure in Colombian coastal and Andean populations on disparities in colorectal adenomas and cancer risk. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr PR08.
Type of Medium:
Online Resource
ISSN:
1055-9965
,
1538-7755
DOI:
10.1158/1538-7755.DISP15-PR08
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2016
detail.hit.zdb_id:
2036781-8
detail.hit.zdb_id:
1153420-5
Permalink
