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

Abstract

BackgroundLimited 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.MethodsThis 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.ResultsMultivariate 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.ConclusionsOur 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 materialThe online version of this article (10.1186/s12967-018-1634-0) contains supplementary material, which is available to authorized users.

MAP3K1 rs889312 polymorphism and cancer prognosis: A systematic review and meta‐analysis

“…After that, the title and abstract of 223 articles were screened and 155 were removed before the full‐text review of 68 articles. Due to not meeting the inclusion criteria, 63 articles were excluded, and finally, five articles 16 , 29 , 30 , 31 , 32 comprising 24 439 patients were included for both qualitative and quantitative data synthesis. Of these articles, three studies were performed on the Chinese population 30 , 31 , 32 from which the outcome and HR (with 95% CI) data of four genetic models, including codominant model 1, codominant model 2, dominant model, and recessive model were collected.…”

“…Due to not meeting the inclusion criteria, 63 articles were excluded, and finally, five articles 16 , 29 , 30 , 31 , 32 comprising 24 439 patients were included for both qualitative and quantitative data synthesis. Of these articles, three studies were performed on the Chinese population 30 , 31 , 32 from which the outcome and HR (with 95% CI) data of four genetic models, including codominant model 1, codominant model 2, dominant model, and recessive model were collected. One study was conducted on a mixed population 29 and one study was performed on the Taiwanese population 16 from which the data of the outcome and HR (with 95% CI) were collected for two genetic models (codominant model 1 and codominant model 2) and one genetic model (recessive model), respectively.…”

“…One study was conducted on a mixed population 29 and one study was performed on the Taiwanese population 16 from which the data of the outcome and HR (with 95% CI) were collected for two genetic models (codominant model 1 and codominant model 2) and one genetic model (recessive model), respectively. Again, three articles were on breast cancer 16 , 29 , 30 and two were on gastric cancer. 31 , 32 The NOS quality score data revealed that all five included articles were of high quality (score ≥7).…”

“…Due to the inconsistencies of previous studies, this meta‐analysis was performed. We have included five studies where three studies were from the Chinese, 30 , 31 , 32 one study was from mixed, 29 and one study was from Taiwanese population. 16 We have collected the HR calculated for different genetic models from these studies and analyzed the effect of rs889312 on cancer prognosis.…”

“… 38 On the other hand, Slattery et al 39 characterized that MAP3K1 was not correlated with the susceptibility of breast tumors in American Hispanic and non‐Hispanic women. In the present study, three articles on breast cancer prognosis were included from Chinese, 30 Taiwanese, 16 and mixed population, 29 which demonstrated a variable association between rs889312 polymorphism and OS of breast cancer. However, based on these inconsistencies, we have conducted the present study incorporating available studies that evaluated the association between cancer prognosis and rs889312 polymorphism.…”