OncoTargets and Therapy (Aug 2019)
MAP3K1 rs889312 genotypes influence survival outcomes of Chinese gastric cancer patients who received adjuvant chemotherapy based on platinum and fluorouracil regimes
Abstract
Jian Yang,1,2,* Wei Zheng,3,* Zhi Xu,1,4 Jinfei Chen1,5,61Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, People’s Republic of China; 2Department of Oncology, The Affiliated Yixing Hospital of Jiangsu University, Yixing 214200, People’s Republic of China; 3Department of General Surgery, The Affiliated Yixing Hospital of Jiangsu University, Yixing 214200, People’s Republic of China; 4ICR Medical Affairs, ICON Plc, Shanghai 200003, People’s Republic of China; 5Cancer Center, TaiKang Xianlin Drum Tower Hospital, Nanjing University School of Medicine, Nanjing 210046, People’s Republic of China; 6Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing 210006, People’s Republic of ChinaCorrespondence: Jinfei ChenDepartment of Oncology, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing 210006, People’s Republic of ChinaTel +86 258 535 8120Fax +86 258 535 8120Email [email protected]*These authors contributed equally to this workBackground: For 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.Methods: The 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.Results: Compared 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).Conclusion: Our 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.Keywords: MAP3K1 rs889312, gastric cancer, biomarker, single-nucleotide polymorphism, adjuvant chemotherapy
