成纤维细胞生长因子受体2（FGFR2）多态性与乳腺癌易感性的关联研究

目的探讨中国女性人群成纤维细胞生长因子受体2（Fibroblast growth factor receptors2,FGFR2）rs2981582C/T、rs2420946C/T以及rs1219648A/G多态性与乳腺癌易感性的关系。方法采用病例-对照研究,以引物介导的限制性多聚酶链反应（PIRA-PCR）和多聚酶链反应-限制性片段长度多态性（PCR-RFLP）方法对673例乳腺癌病例和787例正常对照进行FGFR2基因型检测,采用多元Logistic回归分析基因型与乳腺癌易感性之间的关系。结果 FGFR2三个多态位点的基因型频率分布在病例组和对照组间差异均有统计学意义（P值分别为0.002,0.034和0.002）,其中经调整年龄、月经初潮年龄、绝经状况、哺乳史、生育史、口服避孕药及肿瘤家族史后,rs2420946和rs1219648两位点的变异基因型可增加乳腺癌的发病风险;rs2981582变异基因型也可以增加乳腺癌的发病风险。分层分析结果显示,在绝经前、有哺乳喂养史以及有生育史女性中,3个多态性位点改变对乳腺癌易感性的影响更为显著。结论 FGFR2遗传多态性rs2981582C/T、rs2420946C/T以及rs1219648A/G可增加中国女性罹患乳腺癌的危险性,预期可以作为乳腺癌易感性的重要生物标志物。

Polymorphisms of fibroblast growth factor receptors 2 (FGFR2) and susceptibility of breast cancer

Objective To study the relationship between three loci polymorphisms of fibroblast growth factor receptors 2（FGFR2）,rs2981582 C/T,rs2420946 C/T,rs1219648 A/G,and the susceptibility of breast cancer in Chinese women. Methods Genotypes were determined by the primer-introduced restriction analysis polymerase （PIRA-PCR） and polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） assays in 673 histologically-confirmed breast cancer cases and 787 age and sex frequency-matched cancer-free controls. Results There were significant differences in the genotypes frequencies of 3 loci of FGFR2 gene between cases and controls,with the P value being 0.002,0.034 and 0.002,respectively. After adjusting age,age at menarche,menopausal status,breastfeeding history,reproductive history,oral contraceptive,and family history of cancer,we found that the variant genotypes of both FGFR2 rs2420946 and rs1219648 were significantly associated with the risk of breast cancer,while the variant genotypes of rs2981582 were associated with risk of breast cancer with borderline significance. In stratified analyses,this effect was more evident among premenopausal women,breastfeeding history women and reproductive history women in all polymorphisms. Conclusions These findings suggest that the FGFR2 polymorphisms may contribute to the susceptibility of breast cancer in Chinese women.