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

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.
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.
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.
Our findings highlight FEN1 as an important gene in human breast carcinogenesis and genetic variants in FEN1 confer susceptibility to breast cancer.
AuthorsZheng 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
JournalGene (Gene) Vol. 538 Issue 1 Pg. 42-5 (Mar 15 2014) ISSN: 1879-0038 [Electronic] Netherlands
PMID24440783 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2014 Elsevier B.V. All rights reserved.
Chemical References
  • RNA, Messenger
  • Flap Endonucleases
  • FEN1 protein, human
  • 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)

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