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BMC Cancer
Published in: BMC Cancer 1/2015

Open Access 01-12-2015 | Research article

A functional genetic variant in fragile-site gene FATS modulates the risk of breast cancer in triparous women

Authors: Fangfang Song, Jun Zhang, Li Qiu, Yawen Zhao, Pan Xing, Jiachun Lu, Kexin Chen, Zheng Li

Published in: BMC Cancer | Issue 1/2015

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Abstract

Background

The fragile-site associated tumor suppressor (FATS, formerly known as C10orf90), a regulator of p53-p21 pathway has been involved in the onset of breast cancer. Recent data support the idea that the crosstalk between FATS and p53 may be of physiological importance for reproduction during evolution. The aim of the current study was to test the hypothesis that FATS genetic polymorphism can influence the risk of breast cancer.

Methods

We conducted population-based studies in two independent cohorts comprising 1 532 cases and 1 573 controls in Tianjin of North China, and 804 cases and 835 controls in Guangzhou of South China, coupled with functional validation methods, to investigate the role of FATS genetic variant in breast cancer risk.

Results

We identified a functional variant rs11245007 (905C > T, 262D/N) in fragile-site gene FATS that modulates p53 activation. FATS-262 N exhibited stronger E3 activity to polyubiquitinate p53 than did FATS-262D, leading to the stronger transcriptional activity of p53 and more pronounced stabilization of p53 protein and its activation in response to DNA damage. Case–control studies found that CT or TT genotype was significantly associated with a protective effect on breast cancer risk in women with parity ≥ 3, which was not affected by family history.

Conclusions

Our findings suggest the role of FATS-p53 signaling cascade in suppressing pregnancy-related carcinogenesis and potential application of FATS genotyping in breast cancer prevention.
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Metadata
Title
A functional genetic variant in fragile-site gene FATS modulates the risk of breast cancer in triparous women
Authors
Fangfang Song
Jun Zhang
Li Qiu
Yawen Zhao
Pan Xing
Jiachun Lu
Kexin Chen
Zheng Li
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2015
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-015-1570-9

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