Liang Jie, Chen Peizhan, Hu Zhibin, Zhou Xiaoyi, Chen Lu, Li Mian, Wang Yan, Tang Jinhai, Wang Hui, Shen Hongbing
Laboratory of Reproductive Medicine, Cancer Center, Nanjing Medical University, Nanjing, China.
Carcinogenesis. 2008 Dec;29(12):2341-6. doi: 10.1093/carcin/bgn235. Epub 2008 Oct 8.
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.
成纤维细胞生长因子受体2（FGFR2）属于FGFR家族，该家族在细胞生长、侵袭性、运动性和血管生成中起重要作用。在人类乳腺癌中，FGFR2的表达依赖于雌激素受体（ER），并与较低的凋亡率相关。最近，全基因组关联研究已将FGFR2的几个单核苷酸多态性（SNP）确定为新的乳腺癌易感位点。在本研究中，我们纳入了1049例乳腺癌患者和1073例无癌对照，评估FGFR2的多态性是否与中国女性的乳腺癌风险相关，以及这些关联在有提示更高内源性雌激素暴露的生殖史的女性中是否更强。我们使用SNPstream 12重平台对三个FGFR2多态性（rs2981582C/T、rs1219648A/G和rs2420946C/T）进行基因分型。这三个SNP中的每一个都以剂量依赖的方式与乳腺癌风险增加显著相关。与具有0 - 2个风险位点的女性相比，具有3个风险位点的女性患乳腺癌的几率增加了1.36倍（95%置信区间 = 1.13 - 1.62，P = 0.001）。在分层分析中，在雌激素受体和/或孕激素受体阳性癌症患者、绝经前女性以及首次生育年龄较大的女性中，3个风险位点的存在与乳腺癌之间的关联更强。此外，风险基因型与绝经状态之间存在显著的相加相互作用（乘法相互作用/相加相互作用的P值：0.083/0.037）。这些发现表明，FGFR2中的基因变异可能通过与雌激素和/或孕激素相关的途径促成中国女性乳腺癌的发生。
