Genetic variants in fibroblast growth factor receptor 2 (FGFR2) contribute to susceptibility of breast cancer in Chinese women.
Fibroblast growth factor receptor 2 (FGFR2) belongs to the FGFR family, which plays an important role in cell growth, invasiveness, motility and angiogenesis. In human breast cancer, expression of FGFR2 is estrogen receptor (ER)-dependent and correlates with a lower rate of apoptosis. Recently, whole-genome association studies have identified several single-nucleotide polymorphisms (SNPs) of FGFR2 as novel breast cancer susceptibility loci. In the present study of 1049 breast cancer patients and 1073 cancer-free controls, we assessed whether polymorphisms of FGFR2 are associated with breast cancer risk in Chinese women and whether these associations are stronger in women with a reproductive history suggestive of greater exposure to endogenous estrogens. We genotyped three FGFR2 polymorphisms (rs2981582C/T, rs1219648A/G and rs2420946C/T) using the SNPstream 12-plex platform. Each of the three SNPs was significantly associated with increased breast cancer risk in a dose-dependent manner. Compared with women with 0-2 risk loci, those with 3 risk loci had a 1.36-fold increased odds of breast cancer (95% confidence interval = 1.13-1.62, P = 0.001). In stratified analyses, associations between the presence of 3 risk loci and breast cancer were stronger among women with ER- and/or progesterone receptor-positive cancers, premenopausal women and women with an older age at first live birth. Furthermore, there was a significant additive interaction between risk genotypes and menopausal status (P for multiplication interaction/additive interaction: 0.083/0.037). These findings indicate that genetic variants in FGFR2 may contribute to breast cancer occurrence in Chinese women, possibly through pathways related to estrogen and/or progesterone.
Laboratory of Reproductive Medicine, Cancer Center, Nanjing Medical University, Nanjing, China.
Jie
J
Liang
Peizhan
P
Chen
Zhibin
Z
Hu
Xiaoyi
X
Zhou
Lu
L
Chen
Mian
M
Li
Yan
Y
Wang
Jinhai
J
Tang
Hui
H
Wang
Hongbing
H
Shen
D044466:Asian People / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007150:Immunohistochemistry; D008423:Maternal Age; D008572:Menarche; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D017698:Postmenopause; D017697:Premenopause; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics*; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism
D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C496353:FGFR2 protein, human; D051497:Receptor, Fibroblast Growth Factor, Type 2