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Native American ancestry and breast cancer risk in Colombian and Mexican women: ruling out potential confounding through ancestry-informative markers

BACKGROUND: Latin American and Hispanic women are less likely to develop breast cancer (BC) than women of European descent. Observational studies have found an inverse relationship between the individual proportion of Native American ancestry and BC risk. Here, we use ancestry-informative markers to...

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Autores principales: Zollner, Linda, Torres, Diana, Briceno, Ignacio, Gilbert, Michael, Torres-Mejía, Gabriela, Dennis, Joe, Bolla, Manjeet K., Wang, Qin, Hamann, Ute, Lorenzo Bermejo, Justo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10544431/
https://www.ncbi.nlm.nih.gov/pubmed/37784177
http://dx.doi.org/10.1186/s13058-023-01713-5
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author Zollner, Linda
Torres, Diana
Briceno, Ignacio
Gilbert, Michael
Torres-Mejía, Gabriela
Dennis, Joe
Bolla, Manjeet K.
Wang, Qin
Hamann, Ute
Lorenzo Bermejo, Justo
author_facet Zollner, Linda
Torres, Diana
Briceno, Ignacio
Gilbert, Michael
Torres-Mejía, Gabriela
Dennis, Joe
Bolla, Manjeet K.
Wang, Qin
Hamann, Ute
Lorenzo Bermejo, Justo
author_sort Zollner, Linda
collection PubMed
description BACKGROUND: Latin American and Hispanic women are less likely to develop breast cancer (BC) than women of European descent. Observational studies have found an inverse relationship between the individual proportion of Native American ancestry and BC risk. Here, we use ancestry-informative markers to rule out potential confounding of this relationship, estimating the confounder-free effect of Native American ancestry on BC risk. METHODS AND STUDY POPULATION: We used the informativeness for assignment measure to select robust instrumental variables for the individual proportion of Native American ancestry. We then conducted separate Mendelian randomization (MR) analyses based on 1401 Colombian women, most of them from the central Andean regions of Cundinamarca and Huila, and 1366 Mexican women from Mexico City, Monterrey and Veracruz, supplemented by sensitivity and stratified analyses. RESULTS: The proportion of Colombian Native American ancestry showed a putatively causal protective effect on BC risk (inverse variance-weighted odds ratio [OR] = 0.974 per 1% increase in ancestry proportion, 95% confidence interval [CI] 0.970–0.978, p = 3.1 × 10(–40)). The corresponding OR for Mexican Native American ancestry was 0.988 (95% CI 0.987–0.990, p = 1.4 × 10(–44)). Stratified analyses revealed a stronger association between Native American ancestry and familial BC (Colombian women: OR = 0.958, 95% CI 0.952–0.964; Mexican women: OR = 0.973, 95% CI 0.969–0.978), and stronger protective effects on oestrogen receptor (ER)-positive BC than on ER-negative and triple-negative BC. CONCLUSIONS: The present results point to an unconfounded protective effect of Native American ancestry on BC risk in both Colombian and Mexican women which appears to be stronger for familial and ER-positive BC. These findings provide a rationale for personalised prevention programmes that take genetic ancestry into account, as well as for future admixture mapping studies. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13058-023-01713-5.
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spelling pubmed-105444312023-10-03 Native American ancestry and breast cancer risk in Colombian and Mexican women: ruling out potential confounding through ancestry-informative markers Zollner, Linda Torres, Diana Briceno, Ignacio Gilbert, Michael Torres-Mejía, Gabriela Dennis, Joe Bolla, Manjeet K. Wang, Qin Hamann, Ute Lorenzo Bermejo, Justo Breast Cancer Res Research BACKGROUND: Latin American and Hispanic women are less likely to develop breast cancer (BC) than women of European descent. Observational studies have found an inverse relationship between the individual proportion of Native American ancestry and BC risk. Here, we use ancestry-informative markers to rule out potential confounding of this relationship, estimating the confounder-free effect of Native American ancestry on BC risk. METHODS AND STUDY POPULATION: We used the informativeness for assignment measure to select robust instrumental variables for the individual proportion of Native American ancestry. We then conducted separate Mendelian randomization (MR) analyses based on 1401 Colombian women, most of them from the central Andean regions of Cundinamarca and Huila, and 1366 Mexican women from Mexico City, Monterrey and Veracruz, supplemented by sensitivity and stratified analyses. RESULTS: The proportion of Colombian Native American ancestry showed a putatively causal protective effect on BC risk (inverse variance-weighted odds ratio [OR] = 0.974 per 1% increase in ancestry proportion, 95% confidence interval [CI] 0.970–0.978, p = 3.1 × 10(–40)). The corresponding OR for Mexican Native American ancestry was 0.988 (95% CI 0.987–0.990, p = 1.4 × 10(–44)). Stratified analyses revealed a stronger association between Native American ancestry and familial BC (Colombian women: OR = 0.958, 95% CI 0.952–0.964; Mexican women: OR = 0.973, 95% CI 0.969–0.978), and stronger protective effects on oestrogen receptor (ER)-positive BC than on ER-negative and triple-negative BC. CONCLUSIONS: The present results point to an unconfounded protective effect of Native American ancestry on BC risk in both Colombian and Mexican women which appears to be stronger for familial and ER-positive BC. These findings provide a rationale for personalised prevention programmes that take genetic ancestry into account, as well as for future admixture mapping studies. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13058-023-01713-5. BioMed Central 2023-10-02 2023 /pmc/articles/PMC10544431/ /pubmed/37784177 http://dx.doi.org/10.1186/s13058-023-01713-5 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Zollner, Linda
Torres, Diana
Briceno, Ignacio
Gilbert, Michael
Torres-Mejía, Gabriela
Dennis, Joe
Bolla, Manjeet K.
Wang, Qin
Hamann, Ute
Lorenzo Bermejo, Justo
Native American ancestry and breast cancer risk in Colombian and Mexican women: ruling out potential confounding through ancestry-informative markers
title Native American ancestry and breast cancer risk in Colombian and Mexican women: ruling out potential confounding through ancestry-informative markers
title_full Native American ancestry and breast cancer risk in Colombian and Mexican women: ruling out potential confounding through ancestry-informative markers
title_fullStr Native American ancestry and breast cancer risk in Colombian and Mexican women: ruling out potential confounding through ancestry-informative markers
title_full_unstemmed Native American ancestry and breast cancer risk in Colombian and Mexican women: ruling out potential confounding through ancestry-informative markers
title_short Native American ancestry and breast cancer risk in Colombian and Mexican women: ruling out potential confounding through ancestry-informative markers
title_sort native american ancestry and breast cancer risk in colombian and mexican women: ruling out potential confounding through ancestry-informative markers
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10544431/
https://www.ncbi.nlm.nih.gov/pubmed/37784177
http://dx.doi.org/10.1186/s13058-023-01713-5
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