Association of genetic variants of FBXO32 and FOXO6 in the FOXO pathway with breast cancer risk.

Abstract

Forkhead box class O (FOXO) transcription factors play a pivotal role in regulating a variety of biological processes, including organismal development, cell signaling, cell metabolism, and tumorigenesis. Therefore, we hypothesize that genetic variants in FOXO pathway genes are associated with breast cancer (BC) risk. To test this hypothesis, we conducted a large meta-analysis using 14 published genome-wide association study (GWAS) data sets in the Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE) study. We assessed associations between 5214 (365 genotyped in DRIVE and 4849 imputed) common single-nucleotide polymorphisms (SNPs) in 55 FOXO pathway genes and BC risk. After multiple comparison corrections by the Bayesian false-discovery probability method, we found five SNPs to be significantly associated with BC risk. In stepwise multivariate logistic regression analysis with adjustment for age, principal components, and previously published SNPs in the same data set, three independent SNPs (i.e., FBXO32 rs10093411 A>G, FOXO6 rs61229336 C>T, and FBXO32 rs62521280 C>T) remained to be significantly associated with BC risk (p = 0.0008, 0.0011, and 0.0017, respectively). Additional expression quantitative trait loci analysis revealed that the FBXO32 rs62521280 T allele was associated with decreased messenger RNA (mRNA) expression levels in breast tissue, while the FOXO6 rs61229336 T allele was found to be associated with decreased mRNA expression levels in the whole blood cells. Once replicated by other investigators, these genetic variants may serve as new biomarkers for BC risk.

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Citation

Published Version (Please cite this version)

10.1002/mc.23331

Publication Info

Wang, Haijiao, Hongliang Liu, Lingling Zhao, Sheng Luo, Tomi Akinyemiju, Shelley Hwang, Ying Yue, Qingyi Wei, et al. (2021). Association of genetic variants of FBXO32 and FOXO6 in the FOXO pathway with breast cancer risk. Molecular carcinogenesis. 10.1002/mc.23331 Retrieved from https://hdl.handle.net/10161/23498.

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Scholars@Duke

Luo

Sheng Luo

Professor of Biostatistics & Bioinformatics
Akinyemiju

Tomi Akinyemiju

Professor in Population Health Sciences

Area of Expertise: Epidemiology

Dr. Akinyemiju is a Professor of Population Health Sciences, Global Health and Ob/Gyn with expertise in cancer epidemiology, cancer biology, global health, and health disparities.  Her research expertise and accomplishments have focused on articulating and innovating conceptual and empirical approaches for cancer health disparities research, specifically, disentangling the role of race as a social construct and race-associated biological mechanisms that contribute to cancer disparities. Dr. Akinyemiju also serves as the Vice-Chair for Diversity, Equity, and Inclusion at the Department of Population Health Sciences, and Associate Director for Community Outreach, Engagement, and Equity at the Duke Cancer Institute. Dr. Akinyemiju’s leadership centers around building cross-enterprise, multi-stakeholder coalitions to advance health equity, promote inclusion and diversity, and mentor the next generation of diverse, talented clinical research scholars. Dr. Akinyemiju has received numerous awards, including the 2023 Michelle Winn Inclusive Excellence Award

Dr. Akinyemiju has published over 150 peer-reviewed publications, and her research program has been continuously funded by the National Institutes of Health, Susan G. Komen and the V Foundation. She has mentored (formally and informally) at least 50 trainees and junior faculty, over 50% of whom are URM. Dr. Akinyemiju works extensively with diverse stakeholders, including community-based organizations, policy makers, providers, health system leadership, and leaders from diverse communities to develop impactful, evidence-based interventions to advance health equity 


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