Heterogeneity of Breast Cancer Associations with Common Genetic Variants in FGFR2 according to the Intrinsic Subtypes in Southern Han Chinese Women.
Heterogeneity of Breast Cancer Associations with Common Genetic Variants in FGFR2 according to the Intrinsic Subtypes in Southern Han Chinese Women.
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根据中国南方汉族女性的内在亚型，乳腺癌与 FGFR2 常见遗传变异相关的异质性
DOI：
10.1155/2015/626948
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发表时间：
2015
影响因子：
--
通讯作者：
Li M
中科院分区：
文献类型：
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作者：
Liang H;Yang X;Chen L;Li H;Zhu A;Sun M;Wang H;Li M
Gwas已经确定FGFR2基因的变异是乳腺癌的危险因素。然而，验证性研究显示，根据种族和病理特征得出的结果不一致。为了进一步探讨这种不一致性，并根据中国南方汉族女性固有亚型(Lumina-A、Lumina-B、ER−&PR−和HER2+，以及三重阴性)，研究FGFR2变异与乳腺癌的关系。Rs2420946、rs2981579和rs2981582与乳腺癌风险显著相关，每个风险等位基因的OR(95%CI)分别为1.19(1.03-1.39)、1.24(1.07-1.43)和1.17(1.01-1.36)。在亚型特异性分析中，上述三个SNP与Lumina-A风险的增加呈剂量依赖关系(P趋势P<0.01)，但只有rs2981579与Lumina-B相关，而与ER−和PR−亚型(ER−、PR−、HER2+和三重阴性)无关。单倍型分析还发现常见的单倍型与管腔样亚型(管腔-A和管腔-B)显著相关，但与ER−和PR−亚型无关。我们的结果表明，FGFR2 SNPs与乳腺癌的关联根据固有亚型的不同而不同。未来的研究将根据患者的内在亚型对患者进行分类，这将为乳腺癌背后的复杂遗传机制提供新的见解。
GWAS have identified variation in the FGFR2 locus as risk factors for breast cancer. Validation studies, however, have shown inconsistent results by ethnics and pathological characteristics. To further explore this inconsistency and investigate the associations of FGFR2 variants with breast cancer according to intrinsic subtype (Luminal-A, Luminal-B, ER−&PR−&HER2+, and triple negative) among Southern Han Chinese women, we genotyped rs1078806, rs1219648, rs2420946, rs2981579, and rs2981582 polymorphisms in 609 patients and 882 controls. Significant associations with breast cancer risk were observed for rs2420946, rs2981579, and rs2981582 with OR (95% CI) per risk allele of 1.19 (1.03–1.39), 1.24 (1.07–1.43), and 1.17 (1.01–1.36), respectively. In subtype specific analysis, above three SNPs were significantly associated with increased Luminal-A risk in a dose-dependent manner (P trend < 0.01); however, only rs2981579 was associated with Luminal-B, and none were linked to ER−&PR− subtypes (ER−&PR−&HER2+ and triple negative). Haplotype analyses also identified common haplotypes significantly associated with luminal-like subtypes (Luminal-A and Luminal-B), but not with ER−&PR− subtypes. Our results suggest that associations of FGFR2 SNPs with breast cancer were heterogeneous according to intrinsic subtype. Future studies stratifying patients by their intrinsic subtypes will provide new insights into the complex genetic mechanisms underlying breast cancer.