Clinical importance of TYMS and ENOSF1 genetic variants and mRNA expression levels in response to chemotherapy in Iranian gastric cancer patients

Abstract Background Genetic variants are powerful tools for predicting the effectiveness of chemotherapy drugs. Thymidylate synthase (TS) is a crucial enzyme in gastric cancer patients given neoadjuvant chemotherapy based on 5-Fluorouracil (5-FU). The enolase superfamily member 1 ( ENSOF1 ) variant affects TS gene ( TYMS ) expression and thus may affect chemoresistance in gastric cancer. Hence, this study aims to examine the 28 bp VNTR variant on the 5'UTR of the TYMS gene and rs2612091 and rs2741171 variants of the ENOSF1 and the possible effects of their alleles on chemo-resistance, survival, and gene expression among gastric cancer cases. Methods and Results Genetic analysis was performed on 100 matched FFPE blocks for normal tissues of gastric cancer cases. All patients were treated with neoadjuvant chemotherapy based on 5-FU. RNA was obtained from the tumor and matched normal tissues. The 28 bp VNTR, rs2612091, and 2741171 variants were genotyped, and the gene expression was analyzed using Real-Time PCR. A significant association was observed between genotypes of VNTR and the treatment (p = 0.032). Cases with the 2R3R genotype had a better response to the treatment. The highest and lowest average survival times of patients were observed in the 3R3R and 2R2R genotypes, respectively (p = 0.003). The 3R3R genotype was associated with higher TYMS expression (P < 0.001). There was a significant relationship between genotypes rs2612091 and the treatment (p = 0.017). Conclusions This research indicated that genotyping and gene expression analysis of TYMS and ENOSF1 might be used to predict gastric cancer survival and responsiveness to 5-FU-based neoadjuvant treatment.