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

Publication ,  Journal Article
Wang, H; Liu, H; Zhao, L; Luo, S; Akinyemiju, T; Hwang, S; Yue, Y; Wei, Q
Published in: Mol Carcinog
October 2021

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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Published In

Mol Carcinog

DOI

EISSN

1098-2744

Publication Date

October 2021

Volume

60

Issue

10

Start / End Page

661 / 670

Location

United States

Related Subject Headings

  • Signal Transduction
  • SKP Cullin F-Box Protein Ligases
  • Risk Assessment
  • Polymorphism, Single Nucleotide
  • Oncology & Carcinogenesis
  • Muscle Proteins
  • Humans
  • Genotype
  • Genome-Wide Association Study
  • Genetic Variation
 

Citation

APA
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Wang, H., Liu, H., Zhao, L., Luo, S., Akinyemiju, T., Hwang, S., … Wei, Q. (2021). Association of genetic variants of FBXO32 and FOXO6 in the FOXO pathway with breast cancer risk. Mol Carcinog, 60(10), 661–670. https://doi.org/10.1002/mc.23331
Wang, Haijiao, Hongliang Liu, Lingling Zhao, Sheng Luo, Tomi Akinyemiju, Shelley Hwang, Ying Yue, and Qingyi Wei. “Association of genetic variants of FBXO32 and FOXO6 in the FOXO pathway with breast cancer risk.Mol Carcinog 60, no. 10 (October 2021): 661–70. https://doi.org/10.1002/mc.23331.
Wang H, Liu H, Zhao L, Luo S, Akinyemiju T, Hwang S, et al. Association of genetic variants of FBXO32 and FOXO6 in the FOXO pathway with breast cancer risk. Mol Carcinog. 2021 Oct;60(10):661–70.
Wang, Haijiao, et al. “Association of genetic variants of FBXO32 and FOXO6 in the FOXO pathway with breast cancer risk.Mol Carcinog, vol. 60, no. 10, Oct. 2021, pp. 661–70. Pubmed, doi:10.1002/mc.23331.
Wang H, Liu H, Zhao L, Luo S, Akinyemiju T, Hwang S, Yue Y, Wei Q. Association of genetic variants of FBXO32 and FOXO6 in the FOXO pathway with breast cancer risk. Mol Carcinog. 2021 Oct;60(10):661–670.
Journal cover image

Published In

Mol Carcinog

DOI

EISSN

1098-2744

Publication Date

October 2021

Volume

60

Issue

10

Start / End Page

661 / 670

Location

United States

Related Subject Headings

  • Signal Transduction
  • SKP Cullin F-Box Protein Ligases
  • Risk Assessment
  • Polymorphism, Single Nucleotide
  • Oncology & Carcinogenesis
  • Muscle Proteins
  • Humans
  • Genotype
  • Genome-Wide Association Study
  • Genetic Variation