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.
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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)
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Copyright | Copyright © 2014 Elsevier B.V. All rights reserved. |
Chemical References |
- RNA, Messenger
- Flap Endonucleases
- FEN1 protein, human
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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)
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