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

dc.contributor.author

Wang, Haijiao

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Liu, Hongliang

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Zhao, Lingling

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Luo, Sheng

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Akinyemiju, Tomi

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Hwang, Shelley

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Yue, Ying

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Wei, Qingyi

dc.date.accessioned

2021-08-01T19:27:22Z

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2021-08-01T19:27:22Z

dc.date.issued

2021-07

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2021-08-01T19:27:21Z

dc.description.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 (pā€‰=ā€‰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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0899-1987

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1098-2744

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https://hdl.handle.net/10161/23498

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eng

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Wiley

dc.relation.ispartof

Molecular carcinogenesis

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10.1002/mc.23331

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FOXO pathway

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breast cancer susceptibility

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expression quantitative trait loci analysis

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single-nucleotide polymorphism

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

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Journal article

duke.contributor.orcid

Luo, Sheng|0000-0003-4214-5809

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Akinyemiju, Tomi|0000-0002-1412-3234

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Wei, Qingyi|0000-0002-3845-9445|0000-0003-4115-4439

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School of Medicine

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Duke Cancer Institute

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Population Health Sciences

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Duke Global Health Institute

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Medicine, Medical Oncology

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Duke

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Institutes and Centers

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Basic Science Departments

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University Institutes and Centers

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Institutes and Provost's Academic Units

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Medicine

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Clinical Science Departments

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Duke Clinical Research Institute

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Biostatistics & Bioinformatics

pubs.publication-status

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