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.
Type
Journal articleSubject
FOXO pathwaybreast cancer susceptibility
expression quantitative trait loci analysis
single-nucleotide polymorphism
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https://hdl.handle.net/10161/23498Published Version (Please cite this version)
10.1002/mc.23331Publication Info
Wang, Haijiao; Liu, Hongliang; Zhao, Lingling; Luo, Sheng; Akinyemiju, Tomi; Hwang,
Shelley; ... Wei, Qingyi (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.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
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
mechan
Sheng Luo
Professor of Biostatistics & Bioinformatics
Qingyi Wei
Professor in Population Health Sciences
Qingyi Wei, MD, PhD, Professor in the Department of Medicine, is Associate Director
for Cancer Control and Population Sciences, Co-leader of CCPS and Co-leader of Epidemiology
and Population Genomics (Focus Area 1). He is a professor of Medicine and an internationally
recognized epidemiologist focused on the molecular and genetic epidemiology of head
and neck cancers, lung cancer, and melanoma. His research focuses on biomarkers and
genetic determinants for the DNA repair deficient phenotype and
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