Interaction between genetic ancestry and common breast cancer susceptibility variants in Colombian women

Latino women show lower incidences of breast cancer (BC) than non-Hispanic whites. Large-scale genetic association studies have identified variants robustly associated with BC risk in European women. We examine here the relevance of these variants to Colombian BC and possible interactions with genet...

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Main Authors: Tórres, Maria (Author) , Lorenzo Bermejo, Justo (Author) , González Silos, Rosa (Author) , Boekstegers, Felix (Author) , Plass, Christoph (Author) , Hamann, Ute (Author)
Format: Article (Journal)
Language:English
Published: 2019
In: International journal of cancer
Year: 2019, Volume: 144, Issue: 9, Pages: 2181-2191
ISSN:1097-0215
DOI:10.1002/ijc.32023
Online Access:Verlag, Volltext: https://doi.org/10.1002/ijc.32023
Verlag, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/ijc.32023
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Author Notes:Diana Torres, Justo Lorenzo Bermejo, Karen Garcia Mesa, Michael Gilbert, Ignacio Briceño, Svenja Pohl‐Zeidler, Rosa González Silos, Felix Boekstegers, Christoph Plass and Ute Hamann
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Summary:Latino women show lower incidences of breast cancer (BC) than non-Hispanic whites. Large-scale genetic association studies have identified variants robustly associated with BC risk in European women. We examine here the relevance of these variants to Colombian BC and possible interactions with genetic ancestry. Native American, European and African proportions were estimated for 1022 Colombian BC cases and 1023 controls. Logistic regression was applied to assess the association between 78 variants and BC risk and interactions between the variants and ancestry proportions. We constructed a multifactorial risk score combining established BC risk factors, associated risk variants and individual ancestry proportions. Each 1% increase in the Native American proportion translated into a 2.2% lower BC risk (95% CI: 1.4-2.9). Thirteen variants were associated with BC in Colombian women, with allele frequencies and risk effects partially different from European women. Ancestry proportions moderated the risk effects of two variants. The ability of Native American proportions to separate Colombian cases and controls (area-under-the-curve (AUC) = 0.61) was similar to the discriminative ability of family history of BC in first-degree female relatives (AUC = 0.58) or the combined effect of all 13 associated risk variants (AUC = 0.57). Our findings demonstrate ample potential for individualized BC prevention in Hispanic women taking advantage of individual Native American proportions, information on established susceptibility factors and recently identified common risk variants.
Item Description:First published: 28 November 2018
Gesehen am 23.05.2019
Physical Description:Online Resource
ISSN:1097-0215
DOI:10.1002/ijc.32023