Subtype-specific associations between breast cancer risk polymorphisms and the survival of early-stage breast cancer

BACKGROUND: Limited evidence suggests that inherited predisposing risk variants might affect the disease outcome. In this study, we analyzed the effect of genome-wide association studies—identified breast cancer-risk single nucleotide polymorphisms on survival of early-stage breast cancer patients i...

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Detalles Bibliográficos
Autores principales: Fu, Fangmeng, Guo, Wenhui, Lin, Yuxiang, Zeng, Bangwei, Qiu, Wei, Huang, Meng, Wang, Chuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Research
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6167771/
https://www.ncbi.nlm.nih.gov/pubmed/30285756
http://dx.doi.org/10.1186/s12967-018-1634-0
Descripción
Sumario:BACKGROUND: Limited evidence suggests that inherited predisposing risk variants might affect the disease outcome. In this study, we analyzed the effect of genome-wide association studies—identified breast cancer-risk single nucleotide polymorphisms on survival of early-stage breast cancer patients in a Chinese population. METHODS: This retrospective study investigated the relationship between 21 GWAS-identified breast cancer-risk single nucleotide polymorphisms and the outcome of 1177 early stage breast cancer patients with a long median follow-up time of 174 months. Cox proportional hazards regression models were used to estimate the hazard ratios and their 95% confidence intervals. Primary endpoints were breast cancer special survival and overall survival while secondary endpoints were invasive disease free survival and distant disease free survival. RESULTS: Multivariate survival analysis showed only the rs2046210 GA genotype significantly decreased the risk of recurrence and death for early stage breast cancer. After grouping breast cancer subtypes, significantly reduced survival was associated with the variant alleles of rs9485372 for luminal A and rs4415084 for triple negative breast cancer. Importantly, all three single-nucleotide polymorphisms, rs889312, rs4951011 and rs9485372 had remarkable effects on survival of luminal B EBC, either individually or synergistically. Furthermore, statistically significant multiplicative interactions were found between rs4415084 and age at diagnosis and between rs3803662 and tumor grade. CONCLUSIONS: Our results demonstrate that breast cancer risk susceptibility loci identified by GWAS may influence the outcome of early stage breast cancer patients’ depending on intrinsic tumor subtypes in Chinese women. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12967-018-1634-0) contains supplementary material, which is available to authorized users.

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