Genetic variants in fibroblast growth factor receptor 2 (FGFR2) contribute to susceptibility of breast cancer in Chinese women
Genetic variants in fibroblast growth factor receptor 2 (FGFR2) contribute to susceptibility of breast cancer in Chinese women
复制标题
DOI：
10.1093/carcin/bgn235
复制
发表时间：
2008-12-01
期刊：
影响因子：
4.7
通讯作者：
Shen, Hongbing
中科院分区：
文献类型：
--
作者：
Liang, Jie;Chen, Peizhan;Shen, Hongbing
成纤维细胞生长因子受体2（FGFR 2）属于FGFR家族，在细胞生长、侵袭、运动和血管生成中起重要作用。在人乳腺癌中，FGFR 2的表达是雌激素受体（ER）依赖性的，并与较低的细胞凋亡率相关。最近，全基因组关联研究已经确定了FGFR 2的几个单核苷酸多态性（SNP）作为新的乳腺癌易感基因座。在本研究中，1049例乳腺癌患者和1073例无癌对照，我们评估了FGFR 2多态性是否与中国女性乳腺癌风险相关，以及这些关联是否在生育史提示更多内源性雌激素暴露的女性中更强。我们使用SNPstream 12-plex平台对三种FGFR 2多态性（rs 2981582 C/T、rs 1219648 A/G和rs 2420946 C/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个危险基因座的女性相比，具有3个危险基因座的女性患乳腺癌的几率增加1.36倍（95%置信区间= 1.13-1.62，P = 0.001）。在分层分析中，ER和/或孕激素受体阳性癌症妇女、绝经前妇女和首次活产年龄较大的妇女中，3个危险基因座的存在与乳腺癌之间的关联更强。此外，风险基因型和绝经状态之间存在显著的加性交互作用（乘法交互作用/加性交互作用P值：0.083/0.037）。这些发现表明，FGFR 2基因变异可能通过雌激素和/或孕激素相关途径导致中国女性乳腺癌的发生。
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.