The relationship between the SLC31A1 (protein: copper transporter 1) rs10981694 A > C and ATP7B (protein: P-type adenosine triphosphatase 7B) rs9535828 A > G polymorphisms on the overall survival and disease-free survival of 104 Japanese patients with esophageal squamous cell carcinoma (ESCC) receiving neoadjuvant chemoradiotherapy (CRT) was investigated. Chemotherapy consisted of protracted infusion of 5-fluoracil (800 mg/m2/day) on days 1-5 and cisplatin or nedaplatin (80 mg/m2/day) on day 1. The median (range) follow-up was 47 (6-127) months. The 5-year overall and disease-free survival rates were 71.2% and 60.6%, respectively. The 5-year overall survival rate was significantly higher in patients with the SLC31A1 rs10981694 C allele compared with the rs10981694 A/A genotype (91.7% vs. 65.0%, P = 0.018). The 5-year disease-free survival rate was significantly higher in patients with the SLC31A1 rs10981694 C allele compared with the rs10981694 A/A genotype (79.2% vs. 55.0%, P = 0.043). In addition, univariate and multivariate analyses showed the SLC31A1 rs10981694 A > C polymorphism to be a significant prognostic factor affecting 5-year overall survival after neoadjuvant CRT. However, the overall and disease-free survival rates after surgery did not differ significantly among the ATP7B rs9535828 genotypes. In conclusion, only the SLC31A1 rs10981694 A/A genotype was an independent predictor of a poorer 5-year overall survival. Therefore, in neoadjuvant CRT for ESCC patients, the effect of platinum was affected by the SLC31A1 rs10981694 A > C polymorphism. The presence of this polymorphism should be considered when devising neoadjuvant CRT regimens or treatment strategies for ESCC.
Effects of SLC31A1 and ATP7B polymorphisms on platinum resistance in patients with esophageal squamous cell carcinoma receiving neoadjuvant chemoradiotherapy