J Cancer 2020; 11(22):6507-6515. doi:10.7150/jca.44580 This issue

Research Paper

Genetic variants in the Folic acid Metabolic Pathway Genes predict outcomes of metastatic Colorectal Cancer patients receiving first-line Chemotherapy

Lu Jiang1*, Shuwei Li2*, Ming Yuan3*, Ling Ma1, Yu Lin1, Weiyou Zhu1, Haina Du4, Meilin Wang2, Tao Chen5✉, Lingjun Zhu1✉

1. Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
2. Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center For Cancer Personalized Medicine, Nanjing Medical University, Nanjing 211166, China.
3. Department of Oncology, Jiangyin People's Hospital, Wuxi, China.
4. Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, China.
5. Department of Gastrointestinal Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
*These authors contributed equally to this work.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Citation:
Jiang L, Li S, Yuan M, Ma L, Lin Y, Zhu W, Du H, Wang M, Chen T, Zhu L. Genetic variants in the Folic acid Metabolic Pathway Genes predict outcomes of metastatic Colorectal Cancer patients receiving first-line Chemotherapy. J Cancer 2020; 11(22):6507-6515. doi:10.7150/jca.44580. Available from https://www.jcancer.org/v11p6507.htm

File import instruction

Abstract

Background: The association between genetic variants in the folic acid metabolic pathway genes and survival, as well as the responses to chemotherapy of metastatic colorectal cancer (mCRC) patients has not been reported.

Methods: The association between genetic variants in the folic acid metabolic pathway genes and progression-free survival (PFS) and overall survival (OS) of mCRC patients were analyzed using Cox regression model. The false discovery rate (FDR) correction method was conducted. The logistic regression model was used to explore the effects of the interested genetic variants on disease control rate (DCR). The Cancer Genome Atlas (TCGA) database was applied to compare gene expression differences.

Results: We found that rs3786362 G allele of thymidylate synthase (TYMS) gene was significantly associated with PFS (P = 1.10 × 10-2), OS (P = 2.50 × 10-2) and DCR (P = 5.00 × 10-3). The expression of TYMS was overexpressed in CRC tissues compared with adjacent normal tissues. Furthermore, TYMS expression level decreased with respect to younger age and advanced tumor stage.

Conclusion: Genetic variants in the folic acid metabolic pathway genes might serve as potential prognostic biomarkers for mCRC patients.

Keywords: genetic variants, folic acid, colorectal cancer, chemotherapy