Interaction between genetic ancestry and common breast cancer susceptibility variants in Colombian women. Issue 9 (5th January 2019)

• Record Type: Journal Article
• Authors: Torres, Diana; Lorenzo Bermejo, Justo; Garcia Mesa, Karen; Gilbert, Michael; Briceño, Ignacio; Pohl‐Zeidler, Svenja; González Silos, Rosa; Boekstegers, Felix; Plass, Christoph; Hamann, Ute
• Is Part Of: International journal of cancer. Volume 144:Issue 9(2019)
• Page Start: 2181
• Page End: 2191
• Publication Date: 2019-01-05
• Subjects: breast cancer -- Hispanics -- risk factors -- genetic ancestry -- Colombia; Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.32023
• Languages: English
• ISSNs: 0020-7136

Abstract

Abstract : 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. Abstract : What's new? Increasing Native American ancestry proportions are associated with decreasing breast cancer (BC) risk. This paper examines the contributions of genetic ancestry, established risk factors, and newly identified susceptibility variants to BC risk in a Colombian population with diverse proportions of European, Native American, and African ancestry. The authors demonstrate that individual ancestry proportions predict breast cancer risk in Colombia as accurately as established breast cancer risk factors. They also develop a multifactorial risk score and examine its potential for breast cancer risk prediction. The findings underline the relevance of considering genetic ancestry in the breast cancer care of Hispanic populations.