<p>MAP3K1 rs889312 genotypes influence survival outcomes of Chinese gastric cancer patients who received adjuvant chemotherapy based on platinum and fluorouracil regimes</p>

Abstract

BackgroundFor patients with gastric cancer (GC), adjuvant chemotherapy is a standard therapy. However, the responses to the treatment are quite different. Mitogen-activated protein kinase (MAPK) pathway is a core pathway that modulates the efficacy of anticancer drugs. The purpose of our study was to investigate the clinical significance of one pivotal functional gene polymorphism in the MAPK pathway – MAP3K1 rs889312 – in patients with stage II GC to stage III GC.MethodsThe genotypes of MAP3K1 rs889312 were analyzed in 591 GC patients enrolled in this study who had received radical gastrectomy. Among them, 204 patients accepted adjuvant chemotherapy based on platinum and fluorouracil (PF) regimens after an operation. Cox regression analysis, log-rank test and Kaplan–Meier method were used to explore the link between MAP3K1 rs889312 variant and overall survival (OS) of GC.ResultsCompared with the AA genotype (mean OS of 68.12 months), MAP3K1 rs889312 AC/CC significantly reduced the mean OS of 56.83 months in patients who received adjuvant chemotherapy only. In addition, AC/CC genotype had a negative impact on OS of patients who received oxaliplatin-based therapy (HR, 8.253; 95% CI: 1.119–60.853, log-rank p=0.013). Stratification analysis showed that MAP3K1 rs889312 AC/CC significantly reduced OS of patients with tumors smaller than or equal to 5 cm in size (HR, 3.706; 95% CI: 1.329–10.335, p=0.012), poorly differentiated tumors (HR, 3.002; 95% CI: 1.076–8.377, p=0.036) and intestinal tumors (HR, 4.780; 95% CI: 1.138–20.073, p=0.033).ConclusionOur findings suggested that MAP3K1 rs889312 single-nucleotide polymorphism may be considered as a biomarker for adjuvant chemotherapy reaction and can predict prognosis of GC patients who received PF-based therapy.

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.…”

“…Although the recessive (CC vs. AC + AA) model depicted a better OS, the risk was not statistically significant (HR <1 and p > .05). Wei et al 31 and Yang et al 32 demonstrated that the MAP3K1 rs889312 polymorphism might be considered a prognostic biomarker for gastric cancer development. Fu et al 30 also showed that rs889312 polymorphism substantially influences the prognosis of breast cancer.…”