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

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 a...

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Autores principales: Liang, Huiying, Yang, Xuexi, Chen, Lujia, Li, Hong, Zhu, Anna, Sun, Minying, Wang, Haitao, Li, Ming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4573424/
https://www.ncbi.nlm.nih.gov/pubmed/26421298
http://dx.doi.org/10.1155/2015/626948
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author Liang, Huiying
Yang, Xuexi
Chen, Lujia
Li, Hong
Zhu, Anna
Sun, Minying
Wang, Haitao
Li, Ming
author_facet Liang, Huiying
Yang, Xuexi
Chen, Lujia
Li, Hong
Zhu, Anna
Sun, Minying
Wang, Haitao
Li, Ming
author_sort Liang, Huiying
collection PubMed
description 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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spelling pubmed-45734242015-09-29 Heterogeneity of Breast Cancer Associations with Common Genetic Variants in FGFR2 according to the Intrinsic Subtypes in Southern Han Chinese Women Liang, Huiying Yang, Xuexi Chen, Lujia Li, Hong Zhu, Anna Sun, Minying Wang, Haitao Li, Ming Biomed Res Int Research Article 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. Hindawi Publishing Corporation 2015 2015-09-03 /pmc/articles/PMC4573424/ /pubmed/26421298 http://dx.doi.org/10.1155/2015/626948 Text en Copyright © 2015 Huiying Liang et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Liang, Huiying
Yang, Xuexi
Chen, Lujia
Li, Hong
Zhu, Anna
Sun, Minying
Wang, Haitao
Li, Ming
Heterogeneity of Breast Cancer Associations with Common Genetic Variants in FGFR2 according to the Intrinsic Subtypes in Southern Han Chinese Women
title Heterogeneity of Breast Cancer Associations with Common Genetic Variants in FGFR2 according to the Intrinsic Subtypes in Southern Han Chinese Women
title_full Heterogeneity of Breast Cancer Associations with Common Genetic Variants in FGFR2 according to the Intrinsic Subtypes in Southern Han Chinese Women
title_fullStr Heterogeneity of Breast Cancer Associations with Common Genetic Variants in FGFR2 according to the Intrinsic Subtypes in Southern Han Chinese Women
title_full_unstemmed Heterogeneity of Breast Cancer Associations with Common Genetic Variants in FGFR2 according to the Intrinsic Subtypes in Southern Han Chinese Women
title_short Heterogeneity of Breast Cancer Associations with Common Genetic Variants in FGFR2 according to the Intrinsic Subtypes in Southern Han Chinese Women
title_sort heterogeneity of breast cancer associations with common genetic variants in fgfr2 according to the intrinsic subtypes in southern han chinese women
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4573424/
https://www.ncbi.nlm.nih.gov/pubmed/26421298
http://dx.doi.org/10.1155/2015/626948
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