Association of functional FEN1 genetic variants and haplotypes and breast cancer risk.

Abstract

AIM:

As a tumor suppressor, FEN1 plays an essential role in preventing tumorigenesis. Two functional germline variants (-69G>A and 4150G>T) in the FEN1 gene have been associated with DNA damage levels in coke-oven workers and multiple cancer risk in general populations. However, it is still unknown how these genetic variants are involved in breast cancer susceptibility.

METHODS:

We investigated the association between these polymorphisms and breast cancer risk in two independent case-control sets consisted of a total of 1100 breast cancer cases and 1400 controls. The influence of these variations on FEN1 expression was also examined using breast normal tissues.

RESULTS:

It was found that the FEN1-69GG genotypes were significantly correlated to increased risk for developing breast cancer compared with the -69AA genotype in both sets [Jinan set: odds ratios (OR)=1.41, 95% confidence interval (CI)=1.20-1.65, P=1.9×10(-5); Huaian set: OR=1.51, 95% CI=1.22-1.86, P=1.7×10(-4)]. Similar results were observed for 4150G>T polymorphism. The genotype-phenotype correlation analyses demonstrated that the -69G or 4150G allele carriers had more than 2-fold decreased FEN1 expression in breast tissues compared with -69A or 4150T carriers, suggesting that lower FEN1 expression may lead to higher risk for malignant transformation of breast cells.

CONCLUSION:

Our findings highlight FEN1 as an important gene in human breast carcinogenesis and genetic variants in FEN1 confer susceptibility to breast cancer.

• Authors: Zheng Lv, Weilin Liu, Dongmei Li, Lisheng Liu, Jinyu Wei, Jingfeng Zhang, Yunxia Ge, Zhiqiong Wang, Hongwei Chen, Changchun Zhou, Qipeng Yuan, Liqing Zhou, Ming Yang
• Journal: Gene (Gene) Vol. 538 Issue 1 Pg. 42-5 (Mar 15 2014) ISSN: 1879-0038 [Electronic] Netherlands
• PMID: 24440783 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

• RNA, Messenger
• Flap Endonucleases
• FEN1 protein, human

Topics

• Adult
• Breast Neoplasms (diagnosis, genetics, metabolism)
• Carcinoma (diagnosis, genetics, metabolism)
• Case-Control Studies
• Female
• Flap Endonucleases (genetics, metabolism)
• Genetic Association Studies
• Genetic Predisposition to Disease
• Haplotypes
• Humans
• Middle Aged
• Polymorphism, Single Nucleotide
• RNA, Messenger (genetics, metabolism)