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. 2015:2015:626948.
doi: 10.1155/2015/626948. Epub 2015 Sep 3.

Heterogeneity of Breast Cancer Associations with Common Genetic Variants in FGFR2 according to the Intrinsic Subtypes in Southern Han Chinese Women

Huiying Liang  1 , Xuexi Yang  2 , Lujia Chen  3 , Hong Li  2 , Anna Zhu  2 , Minying Sun  4 , Haitao Wang  5 , Ming Li  2
Affiliations

Heterogeneity of Breast Cancer Associations with Common Genetic Variants in FGFR2 according to the Intrinsic Subtypes in Southern Han Chinese Women

Huiying Liang et al. Biomed Res Int. 2015.

Abstract

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.

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Figures

Figure 1
Figure 1
Classification of breast cancer tumors according to the expression of ER, PR, HER2, and Ki67 (tumor subtype nomenclature explanation: / = “and/or,” & = “and”).
Figure 2
Figure 2
Linkage disequilibrium analyses of the four FGFR2 SNPs among Southern Han Chinese women.
Figure 3
Figure 3
Associations of haplotypes of FGFR2 rs1078806, rs2420946, rs2981579, and rs2981582 with breast cancer by subtype (x-axis: OR adjusted for age, age at first full-term pregnancy, menopausal status, and hormonal therapy status; horizontal bars showing 95% CIs.).
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