Carcinogenesis Advance Access originally published online on October 8, 2008
Carcinogenesis 2008 29(12):2341-2346; 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
Laboratory of Reproductive Medicine, Cancer Center, Nanjing Medical University, 140 Hanzhong Road, Nanjing 210029, China
1 Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, People's Republic of China
2 Department of General Surgery, Jiangsu Cancer Hospital, Nanjing 210009, China
* To whom correspondence should be addressed. Tel/Fax: +86 25 868 62756; Email: hbshen{at}njmu.edu.cn
Correspondence may also be addressed to Hui Wang. Tel/Fax: +86 21 5492 0941; Email: 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 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.
Abbreviations: CI, confidence interval; ER, estrogen receptor; FGFR2, fibroblast growth factor receptor 2; LD, linkage disequilibrium; OR, odds ratio; PR, progesterone receptor; SNP, single-nucleotide polymorphism
These authors contributed equally to this work. Received June 19, 2008; revised September 15, 2008; accepted September 30, 2008.
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