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Germline HOXB13 mutations p.G84E and p.R217C do not confer an increased breast cancer risk.

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

Liu, Jingjing 
Prager-van der Smissen, Wendy JC 
Collée, J Margriet 
Bolla, Manjeet K 
Wang, Qin 

Abstract

In breast cancer, high levels of homeobox protein Hox-B13 (HOXB13) have been associated with disease progression of ER-positive breast cancer patients and resistance to tamoxifen treatment. Since HOXB13 p.G84E is a prostate cancer risk allele, we evaluated the association between HOXB13 germline mutations and breast cancer risk in a previous study consisting of 3,270 familial non-BRCA1/2 breast cancer cases and 2,327 controls from the Netherlands. Although both recurrent HOXB13 mutations p.G84E and p.R217C were not associated with breast cancer risk, the risk estimation for p.R217C was not very precise. To provide more conclusive evidence regarding the role of HOXB13 in breast cancer susceptibility, we here evaluated the association between HOXB13 mutations and increased breast cancer risk within 81 studies of the international Breast Cancer Association Consortium containing 68,521 invasive breast cancer patients and 54,865 controls. Both HOXB13 p.G84E and p.R217C did not associate with the development of breast cancer in European women, neither in the overall analysis (OR = 1.035, 95% CI = 0.859-1.246, P = 0.718 and OR = 0.798, 95% CI = 0.482-1.322, P = 0.381 respectively), nor in specific high-risk subgroups or breast cancer subtypes. Thus, although involved in breast cancer progression, HOXB13 is not a material breast cancer susceptibility gene.

Description

Keywords

Breast Neoplasms, Female, Genetic Predisposition to Disease, Genotyping Techniques, Germ-Line Mutation, Homeodomain Proteins, Humans, Middle Aged, Risk Factors

Journal Title

Sci Rep

Conference Name

Journal ISSN

2045-2322
2045-2322

Volume Title

10

Publisher

Springer Science and Business Media LLC

Rights

All rights reserved
Sponsorship
Cancer Research Uk (None)
Cancer Research UK (16565)
Medical Research Council (G1000143)
National Cancer Institute (U19CA148537)
National Cancer Institute (U19CA148065)
Cancer Research UK (10710)
Cancer Research UK (16563)
Cancer Research UK (12014)
Cancer Research UK (10118)
Cancer Research Uk (None)
National Institutes of Health (NIH) (via Dana-Farber Cancer Institute) (1282801)
Medical Research Council (G0500300)
Medical Research Council (G0401527)
Medical Research Council (MR/N003284/1)
European Commission Horizon 2020 (H2020) Societal Challenges (634935)
European Commission Horizon 2020 (H2020) Societal Challenges (633784)
Wellcome Trust (203477/Z/16/Z)
Medical Research Council (G0401527/1)