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

Gene. 2014 Mar 15;538(1):42-5. doi: 10.1016/j.gene.2014.01.025. Epub 2014 Jan 16.


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.

Keywords: FEN1; breast cancer; haplotype; polymorphism; susceptibility.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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


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