Carcinogenesis Advance Access published online on October 8, 2008
Carcinogenesis, doi:10.1093/carcin/bgn235
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Genetic variants in fibroblast growth factor receptor 2 (FGFR2) contribute to susceptibility of breast cancer in Chinese women
1 Laboratory of Reproductive Medicine, Cancer Center, Nanjing Medical University, Nanjing 210029, China
2 Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, P. R. China
3 Department of General Surgery, Jiangsu Cancer Hospital
* Correspondence to: Dr. Hongbing Shen, Laboratory of Reproductive Medicine, Cancer Center, Nanjing Medical University, 140 Hanzhong Rd., Nanjing 210029, China. Tel (Fax): +86-25-868-62756. E-mail: hbshen{at}njmu.edu.cn
Co-correspondence to: Dr. Hui Wang, E-mail: huiwang{at}sibs.ac.cn.
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 1,049 breast cancer patients and 1,073 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 to women with 0-2 risk loci, those with 3 risk loci had a 1.36-fold increased odds of breast cancer (95% CI = 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 (PR)-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.
Key Words: FGFR2 • polymorphisms • breast cancer • molecular epidemiology
These authors contributed equally to this work. Received June 19, 2008; revised September 15, 2008; accepted September 30, 2008.
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