MTNR1B polymorphisms with CDKN2A and MGMT methylation status are associated with poor prognosis of colorectal cancer in Taiwan  

作　　者：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 

机构地区：[1]Division of Colorectal Surgery,Department of Surgery,Tri-Service General Hospital,National Defense Medical Center,Taipei 114,Taiwan,China [2]Medical Informatics Office,Tri-Service General Hospital,National Defense Medical Center,Taipei 114,Taiwan,China [3]School of Public Health,National Defense Medical Center,Taipei 114,Taiwan,China [4]Department of Public Health,College of Medicine,Fu-Jen Catholic University,New Taipei City 24205,Taiwan,China [5]Big Data Research Center,College of Medicine,Fu-Jen Catholic University,New Taipei City 24205,Taiwan,China [6]Department of Health Business Administration,Meiho University,Pingtung 91202,Taiwan,China [7]Department and Graduate Institute of Microbiology and Immunology,National Defense Medical Center,Taipei 114,Taiwan,China [8]Institute of Preventive Medicine,National Defense Medical Center,New Taipei City 237,Taiwan,China

出　　处：《World Journal of Gastroenterology》2021年第34期5737-5752,共16页世界胃肠病学杂志（英文版）

基　　金：the grant from the Ministry of National Defense-Medical Affairs Bureau,Taiwan,No.MND-MAB-110-109 and No.MND-MAB-D-111059.

摘　　要：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.

关 键 词：Colorectal cancer MELATONIN HYPERMETHYLATION Polymorphism Prognosis Biomarker 

分 类 号：R735.34[医药卫生—肿瘤]