FGFR3基因单核苷酸多态与绝经前乳腺癌易感性的关联研究

Association between single nucleotide polymorphisms in FGFR3 gene and risk of breast cancer

目的探讨FGFR3基因单核苷酸多态(SNPs)与女性绝经前乳腺癌的风险关系。方法采用多重单碱基延伸SNP分型技术(Snapshot)检测FGFR3基因的rs2234909和rs3135848的SNP基因型在绝经前乳腺癌患者和绝经前正常女性人群中的频率,并分析不同SNP基因型与绝经前乳腺癌发病的风险关系。结果 FGFR3基因rs2234909和rs3135848的SNP基因型的频率在乳腺癌与对照组间无统计学差异(P>0.05)。Logistic回归分析结果显示,对于rs2234909位点,相比较于TT基因型,TC和TC+CC基因型和乳腺癌的发病风险无显著相关性(OR=1.035,95%CI:0.680～1.575,P=0.874;OR=0.985,95%CI:0.638～1.521,P=0.945);对于rs3135848位点,相比较于TT基因型,TC、CC和TC+CC基因型与乳腺癌的发病风险无关(OR=1.177,95%CI:0.846～1.636,P=0.333;OR=0.948,95%CI:0.287～3.137,P=0.931;OR=1.162,95%CI:0.548～1.112,P=0.360)。rs2234909位点突变的乳腺癌患者与未突变者相比,组织学分级(显性模型:P=0.032;共显性模型:P=0.024)以及Ki67指数(显性模型:P=0.056;共显性模型:P=0.044)显著增高;rs3135848位点突变及两位点均突变与乳腺癌患者临床病理特征无显著相关性(P>0.05)。结论 FGFR3基因的rs2234909和rs3135848两位点基因多态性与乳腺癌易感性无明显相关性;而rs2234909位点突变在绝经前乳腺癌患者中与组织学分级和Ki67指数呈正相关,可能提示预后不良。

Objective The aim of this study was to investigate the association between single nucleotide polymorphisms（ SNPs） in FGFR3 gene and the risk of breast cancer. Methods The frequency of SNP genotypes rs2234909 and rs3135848 of FGFR3 gene in premenopausal breast cancer patients and premenopausal normal females were detected by multiple clonal extension SNP typing technique. The SNP genotypes were compared with different SNP genotypes and the risk of premenopausal breast cancer. Results There was no difference in the genotype frequencies of SNP rs2234909 and rs3135848 between breast cancer and control groups（ P 0. 05）. Logistic regression analysis showed that there was no correlation between TC and TC ＋ CC genotype and risk of breast cancer（ OR = 1. 035,95% CI： 0. 680 ～ 1. 575,P = 0. 874; OR = 0. 985,95% CI： 0. 638 ～ 1. 521,P = 0.945）. For the rs3135848 locus,the genotypes of TC,CC and TC ＋ CC were not associated with the risk of breast cancer（ OR = 1. 177,95% CI： 0. 846-1. 636,P = 0. 333; OR = 0. 948,95% CI： 0. 287-3. 137,P = 0. 931; OR= 1. 162,95% CI： 0. 548 ～ 1. 112,P = 0. 360）. Histological grade was significantly higher in breast cancer with rs2234909 mutation than that of the non-mutation group（ dominant model： P = 0. 032,co-dominant model： P =0. 024）. The Ki67 index of FGFR3 gene locus rs2234909 mutation was higher than that of the non-mutation（ dominant model： P = 0. 056; co-dominant model： P = 0. 044）. There was no difference between rs3135848 mutation and both site mutation with clinicopathological features of breast cancer patients（ P 0. 05）. Conclusion The SNP genotypes of rs2234909 and rs3135848 of FGFR3 gene were not associated with susceptibility to breast cancer in premenopausal women in North of China. Rs2234909 mutation was positively correlated with histological grade and Ki67 index in premenopausal breast cancer patients.