Breast Surgery Ward, Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, Fujian Province, China.
Nosocomial Infection Control Branch, Fujian Medical University Union Hospital, Fuzhou, 350001, Fujian Province, China.
J Transl Med. 2018 Oct 1;16(1):270. doi: 10.1186/s12967-018-1634-0.
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.
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.
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.
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.
有限的证据表明，遗传易感性风险变异可能会影响疾病的结局。在这项研究中，我们分析了全基因组关联研究确定的乳腺癌风险单核苷酸多态性对中国人群早期乳腺癌患者生存的影响。
本回顾性研究调查了 21 个全基因组关联研究确定的乳腺癌风险单核苷酸多态性与 1177 例早期乳腺癌患者结局之间的关系，这些患者的中位随访时间长达 174 个月。Cox 比例风险回归模型用于估计风险比及其 95%置信区间。主要终点是乳腺癌特殊生存和总生存，次要终点是无侵袭性疾病生存和无远处疾病生存。
多变量生存分析表明，只有 rs2046210GA 基因型显著降低了早期乳腺癌的复发和死亡风险。在分组乳腺癌亚型后，rs9485372 对 luminal A 和 rs4415084 对三阴性乳腺癌的变异等位基因与生存率显著降低相关。重要的是，所有三个单核苷酸多态性(rs889312、rs4951011 和 rs9485372)对 luminal B EBC 的生存均有显著影响，无论是单独还是协同作用。此外，还发现 rs4415084 与诊断时年龄之间以及 rs3803662 与肿瘤分级之间存在显著的乘法交互作用。
我们的研究结果表明，全基因组关联研究确定的乳腺癌风险易感性位点可能会影响中国女性早期乳腺癌患者的结局，这取决于内在的肿瘤亚型。
