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Genetic susceptibility to type 2 diabetes and breast cancer risk in women of European and African ancestry.

ABSTRACT: Epidemiologic studies have reported a positive association between type 2 diabetes (T2D) and breast cancer risk, independent of body weight.We investigated 40 genetic variants known to be associated with T2D in relation to breast cancer risk among 2,651 breast cancer cases and 2,520 controls of African or European ancestry that were pooled from seven studies.We found that two T2D risk alleles in Caucasian women (rs5945326-G, rs12518099-C) and one in women of African ancestry (rs7578597-T) were positively associated with breast cancer risk at a nominal significance level of 0.05, whereas two T2D risk alleles were inversely associated with breast cancer risk in Caucasian women (rs1111875-C, rs10923931-T). The composite T2D susceptibility score (the number of risk allele) was not significantly associated with breast cancer risk.The association between established T2D genetic susceptibility variants and breast cancer risk in women of African or European ancestry is likely weak, if it does exist.The pleiotropic effects of known T2D risk alleles cannot explain the association between T2D and breast cancer risk.

SUBMITTER: Hou N

PROVIDER: S-EPMC3297695 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

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Genetic susceptibility to type 2 diabetes and breast cancer risk in women of European and African ancestry.

Hou Ningqi N Zheng Yonglan Y Gamazon Eric R ER Ogundiran Temidayo O TO Adebamowo Clement C Nathanson Katherine L KL Domchek Susan M SM Rebbeck Timothy R TR Simon Michael S MS John Esther M EM Hennis Anselm A Nemesure Barbara B Wu Suh-Yuh SY Leske M Cristina MC Ambs Stefan S Niu Qun Q Zhang Jing J Pierce Brandon B Cox Nancy J NJ Olopade Olufunmilayo I OI Huo Dezheng D

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20120111 3

<h4>Background</h4>Epidemiologic studies have reported a positive association between type 2 diabetes (T2D) and breast cancer risk, independent of body weight.<h4>Methods</h4>We investigated 40 genetic variants known to be associated with T2D in relation to breast cancer risk among 2,651 breast cancer cases and 2,520 controls of African or European ancestry that were pooled from seven studies.<h4>Results</h4>We found that two T2D risk alleles in Caucasian women (rs5945326-G, rs12518099-C) and on ...[more]

PMID: 22237986

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Project description:ImportanceMultiple polygenic risk scores (PRSs) for breast cancer have been developed from large research consortia; however, their generalizability to diverse clinical settings is unknown.ObjectiveTo examine the performance of previously developed breast cancer PRSs in a clinical setting for women of European, African, and Latinx ancestry.Design, setting, and participantsThis cohort study using the Electronic Medical Records and Genomics (eMERGE) network data set included 39 591 women from 9 contributing medical centers in the US that had electronic medical records (EMR) linked to genotype data. Breast cancer cases and controls were identified through a validated EMR phenotyping algorithm.Main outcomes and measuresMultivariable logistic regression was used to assess the association between breast cancer risk and 7 previously developed PRSs, adjusting for age, study site, breast cancer family history, and first 3 ancestry informative principal components.ResultsThis study included 39 591 women: 33 594 with European, 3801 with African, and 2196 with Latinx ancestry. The mean (SD) age at breast cancer diagnosis was 60.7 (13.0), 58.8 (12.5), and 60.1 (13.0) years for women with European, African, and Latinx ancestry, respectively. PRSs derived from women with European ancestry were associated with breast cancer risk in women with European ancestry (highest odds ratio [OR] per 1-SD increase, 1.46; 95% CI, 1.41-1.51), women with Latinx ancestry (highest OR, 1.31; 95% CI, 1.09-1.58), and women with African ancestry (OR, 1.19; 95% CI, 1.05-1.35). For women with European ancestry, this association with breast cancer risk was largest in the extremes of the PRS distribution, with ORs ranging from 2.19 (95% CI, 1.84-2.53) to 2.48 (95% CI, 1.89-3.25) for the 3 different PRSs examined for those in the highest 1% of the PRS compared with those in the middle quantile. Among women with Latinx and African ancestries at the extremes of the PRS distribution, there were no statistically significant associations.Conclusions and relevanceThis cohort study found that PRS models derived from women with European ancestry for breast cancer risk generalized well for women with European, Latinx, and African ancestries across different clinical settings, although the effect sizes for women with African ancestry were smaller, likely because of differences in risk allele frequencies and linkage disequilibrium patterns. These results highlight the need to improve representation of diverse population groups, particularly women with African ancestry, in genomic research cohorts.

Dataset Information

Genetic susceptibility to type 2 diabetes and breast cancer risk in women of European and African ancestry.

Publications

Genetic susceptibility to type 2 diabetes and breast cancer risk in women of European and African ancestry.

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