Native American ancestry and breast cancer risk in Colombian and Mexican women: ruling out potential confounding through ancestry-informative markers
Abstract 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 ma...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-10-01
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| Series: | Breast Cancer Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13058-023-01713-5 |
| _version_ | 1797450979561439232 |
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| author | Linda Zollner Diana Torres Ignacio Briceno Michael Gilbert Gabriela Torres-Mejía Joe Dennis Manjeet K. Bolla Qin Wang Ute Hamann Justo Lorenzo Bermejo |
| author_facet | Linda Zollner Diana Torres Ignacio Briceno Michael Gilbert Gabriela Torres-Mejía Joe Dennis Manjeet K. Bolla Qin Wang Ute Hamann Justo Lorenzo Bermejo |
| author_sort | Linda Zollner |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-09T14:48:20Z |
| format | Article |
| id | doaj.art-6a309ffcf67f494aa1790beb1d4ae719 |
| institution | Directory Open Access Journal |
| issn | 1465-542X |
| language | English |
| last_indexed | 2024-03-09T14:48:20Z |
| publishDate | 2023-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Breast Cancer Research |
| spelling | doaj.art-6a309ffcf67f494aa1790beb1d4ae7192023-11-26T14:37:42ZengBMCBreast Cancer Research1465-542X2023-10-0125111310.1186/s13058-023-01713-5Native American ancestry and breast cancer risk in Colombian and Mexican women: ruling out potential confounding through ancestry-informative markersLinda Zollner0Diana Torres1Ignacio Briceno2Michael Gilbert3Gabriela Torres-Mejía4Joe Dennis5Manjeet K. Bolla6Qin Wang7Ute Hamann8Justo Lorenzo Bermejo9Statistical Genetics Research Group, Institute of Medical Biometry, Heidelberg UniversityMolecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ)Instituto de Genética Humana, Universidad de la SabanaMolecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ)Center for Population Health Research, National Institute of Public HealthCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of CambridgeCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of CambridgeCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of CambridgeMolecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ)Statistical Genetics Research Group, Institute of Medical Biometry, Heidelberg UniversityAbstract 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.https://doi.org/10.1186/s13058-023-01713-5Genetic admixtureAncestry-informative markersCausal inferenceInstrumental variablesMendelian randomization |
| spellingShingle | Linda Zollner Diana Torres Ignacio Briceno Michael Gilbert Gabriela Torres-Mejía Joe Dennis Manjeet K. Bolla Qin Wang Ute Hamann Justo Lorenzo Bermejo Native American ancestry and breast cancer risk in Colombian and Mexican women: ruling out potential confounding through ancestry-informative markers Breast Cancer Research Genetic admixture Ancestry-informative markers Causal inference Instrumental variables Mendelian randomization |
| 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 | Genetic admixture Ancestry-informative markers Causal inference Instrumental variables Mendelian randomization |
| url | https://doi.org/10.1186/s13058-023-01713-5 |
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