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©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
MTNR1B polymorphisms with CDKN2A and MGMT methylation status are associated with poor prognosis of colorectal cancer in Taiwan
Chia-Cheng Lee, Yu-Cheng Kuo, Je-Ming Hu, Pi-Kai Chang, Chien-An Sun, Tsan Yang, Chuan-Wang Li, Chao-Yang Chen, Fu-Huang Lin, Chih-Hsiung Hsu, Yu-Ching Chou
Chia-Cheng Lee, Je-Ming Hu, Pi-Kai Chang, Chao-Yang Chen, Division of Colorectal Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan
Chia-Cheng Lee, Medical Informatics Office, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan
Yu-Cheng Kuo, Fu-Huang Lin, Chih-Hsiung Hsu, Yu-Ching Chou, School of Public Health, National Defense Medical Center, Taipei 114, Taiwan
Chien-An Sun, Department of Public Health, College of Medicine, Fu-Jen Catholic University, New Taipei City 24205, Taiwan
Chien-An Sun, Big Data Research Center, College of Medicine, Fu-Jen Catholic University, New Taipei City 24205, Taiwan
Tsan Yang, Department of Health Business Administration, Meiho University, Pingtung 91202, Taiwan
Chuan-Wang Li, Department and Graduate Institute of Microbiology and Immunology, National Defense Medical Center, Taipei 114, Taiwan
Chuan-Wang Li, Institute of Preventive Medicine, National Defense Medical Center, New Taipei City 237, Taiwan
Author contributions: Hsu CH and Chou YC contributed equally to this work; Lee CC, Hsu CH and Chou YC designed the research; Sun CA, Yang T and Li CW performed the research; Hu JM, Chang PK and Chen CY collected the data; Lee CC, Kuo YC, Hsu CH, Lin FH and Chou YC analyzed the data; Lee CC, Hsu CH and Chou YC wrote the paper.
Supported by the grant from the Ministry of National Defense-Medical Affairs Bureau, Taiwan, No. MND-MAB-110-109 and No. MND-MAB-D-111059.
Institutional review board statement: This study was approved by the TSGH Institutional Review Board (TSGHIRB approval number: 098-05-292 and 2-105-05-129).
Informed consent statement: Written informed consent was obtained from all patients before enrollment into the study to evaluate their prognosis.
Conflict-of-interest statement: We have no financial relationships to disclose.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
http://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Yu-Ching Chou, PhD, Professor, School of Public Health, National Defense Medical Center, No. 161 Sec. 6, Minquan E. Road, Neihu District, Taipei 114, Taiwan. trishow@mail.ndmctsgh.edu.tw
Received: April 15, 2021
Peer-review started: April 15, 2021
First decision: June 23, 2021
Revised: June 30, 2021
Accepted: August 23, 2021
Article in press: August 23, 2021
Published online: September 14, 2021
BACKGROUND
Identifying novel colorectal cancer (CRC) prognostic biomarkers is crucial to helping clinicians make appropriate therapy decisions. Melatonin plays a major role in managing the circadian rhythm and exerts oncostatic effects on different kinds of tumours.
AIM
To explore the relationship between MTNR1B single-nucleotide polymorphism (SNPs) combined with gene hypermethylation and CRC prognosis.
METHODS
A total of 94 CRC tumour tissues were investigated. Genotyping for the four MTNR1B SNPs (rs1387153, rs2166706, rs10830963, and rs1447352) was performed using multiplex polymerase chain reaction. The relationships between the MTNR1B SNPs and CRC 5-year overall survival (OS) was assessed by calculating hazard ratios with 95%CIs.
RESULTS
All SNPs (rs1387153, rs2166706, rs10830963, and rs1447352) were correlated with decreased 5-year OS. In stratified analysis, rs1387153, rs10830963, and rs1447352 risk genotype combined with CDKN2A and MGMT methylation status were associated with 5-year OS. A strong cumulative effect of the four polymorphisms on CRC prognosis was observed. Four haplotypes of MTNR1B SNPs were also associated with the 5-year OS. MTNR1B SNPs combined with CDKN2A and MGMT gene methylation status could be used to predict shorter CRC survival.
CONCLUSION
The novel genetic biomarkers combined with epigenetic biomarkers may be predictive tool for CRC prognosis and thus could be used to individualise treatment for patients with CRC.
Core Tip: In this retrospective cohort study, we found that MTNR1B single-nucleotide polymorphism were associated with a significantly increased risk of colorectal cancer (CRC) 5-year overall survival. A strong cumulative effect of the four polymorphisms on CRC prognosis was observed. This study indicated the novel genetic biomarkers, MTNR1B, combined with CDKN2A and MGMT gene methylation statuses, maybe a predictive tool for CRC prognosis.
