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


CONCLUSIONS
Our findings highlight FEN1 as an important gene in human breast carcinogenesis and genetic variants in FEN1 confer susceptibility to breast cancer.
Cancer Center, The First Affiliated Hospital of Jilin University, Changchun, Jilin Province, China.
Zheng
Z
Lv
College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China.
Weilin
W
Liu
Clinical Laboratory, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, Jinan, Shandong Province, China.
Dongmei
D
Li
Clinical Laboratory, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, Jinan, Shandong Province, China.
Lisheng
L
Liu
College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China.
Jinyu
J
Wei
College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China.
Jingfeng
J
Zhang
College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China.
Yunxia
Y
Ge
College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China.
Zhiqiong
Z
Wang
College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China.
Hongwei
H
Chen
Clinical Laboratory, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, Jinan, Shandong Province, China.
Changchun
C
Zhou
College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China.
Qipeng
Q
Yuan
Department of Radiation Oncology, Huaian No. 2 Hospital, Huaian, Jiangsu Province, China. Electronic address: zlq-hill@163.com.
Liqing
L
Zhou
College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China. Electronic address: yangm@mail.buct.edu.cn.
Ming
M
Yang
D000328:Adult; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D002277:Carcinoma / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D045585:Flap Endonucleases / Q000235:genetics* / Q000378:metabolism; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D012333:RNA, Messenger; D045585:Flap Endonucleases; C468317:FEN1 protein, human
FEN1; breast cancer; haplotype; polymorphism; susceptibility