Observational Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Pathophysiol. Nov 22, 2021; 12(6): 134-146
Published online Nov 22, 2021. doi: 10.4291/wjgp.v12.i6.134
Prediction of hereditary nonpolyposis colorectal cancer using mRNA MSH2 quantitative and the correlation with nonmodifiable factor
Tjahjadi Robert Tedjasaputra, Mochammad Hatta, Muh Nasrum Massi, Rosdiana Natzir, Agussalim Bukhari, Rina Masadah, Muh Lutfi Parewangi, Prihantono Prihantono, Rinda Nariswati, Vincent Tedjasaputra
Tjahjadi Robert Tedjasaputra, Department of Internal Medicine, Tarakan General Hospital, Medical Faculty University of Hasanuddin, Jakarta 10720, DKI Jakarta, Indonesia
Mochammad Hatta, Department of Immunology and Biomolecular, Hasanuddin University, Makassar 90245, South Sulawesi, Indonesia
Muh Nasrum Massi, Department of Microbiology, Faculty of Medicine, University of Hasanuddin, Makassar 90245, South Sulawesi, Indonesia
Rosdiana Natzir, Department of Biochemistry Meidcal Faculty, University of Hasanuddin, Makassar 90245, South Sulawesi, Indonesia
Agussalim Bukhari, Department of Nutrition, Faculty of Medicine, Hasanuddin University, Makassar 90245, South Sulawesi, Indonesia
Rina Masadah, Department of Pathology Anatomy, Faculty of Medicine, Hasanuddin University, Makassar 20945, South Sulawesi, Indonesia
Muh Lutfi Parewangi, Department of Internal Medicine, Faculty of Medicine, Hasanuddin University, Makassar 20945, South Sulawesi, Indonesia
Prihantono Prihantono, Department of Surgery, Faculty of Medicine, Hasanuddin University, Makassar 90245, South Sulawesi, Indonesia
Rinda Nariswati, Department of Statistic, School of Computer Science, Bina Nusantara University Jakarta, Jakarta 11530, Indonesia
Vincent Tedjasaputra, American Association for the Advancement of Science (AAAS), Science and Technology Policy Fellow, Alexandria, VA 22314, United States
Author contributions: Tedjasaputra TR and Hatta M conceptualize and design the study; Tedjasaputra V provided administrative support for the study; Tedjasaputra TR and Hatta M give provisions of study materials or patients and commence data collection; all authors write the manuscript and give final approval; Tedjasaputra TR and Natzir R analyze and interpret the data; Massi MN, Nariswati R, Bukhari A, Masadah R, Parewangi ML, and Prihantono P revised the article critically for important intellectual content.
Institutional review board statement: The study follows the international review ethical board with approval from the Hasanuddin University Ethics Committee (Indonesia).
Informed consent statement: All respondents have agreed, understood, and signed the inform consent before commencing further into the study.
Conflict-of-interest statement: The authors declare no conflict of interest. The authors acknowledge that although Vincent Tedjasaputra is currently an American Association for the Advancement of Science (AAAS) Science and Technology Policy Fellow; yet, the current paper is not affiliated with AAAS nor is the product of his position at the National Science Foundation.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
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: Tjahjadi Robert Tedjasaputra, MD, PhD, Consultant Physician-Scientist, Doctor, Senior Lecturer, Department of Internal Medicine, Tarakan General Hospital, Medical Faculty University of Hasanuddin, Jl. Gunung Sahari XI Dalam 70B RT8 RW 3, Jakarta 10720, DKI Jakarta, Indonesia. rtedjasaputra@yahoo.com
Received: January 27, 2021
Peer-review started: January 27, 2021
First decision: March 1, 2021
Revised: March 13, 2021
Accepted: October 11, 2021
Article in press: October 11, 2021
Published online: November 22, 2021
Processing time: 293 Days and 8.4 Hours
Abstract
BACKGROUND

Hereditary non-polyposis colon cancer is a dominantly inherited syndrome of colorectal cancer (CRC), with heightened risk for younger population. Previous studies link its susceptibility to the DNA sequence polymorphism along with Amsterdam and Bethesda criteria. However, those fail in term of applicability.

AIM

To determine a clear cut-off of MSH2 gene expression for CRC heredity grouping factor. Further, the study also aims to examine the association of risk factors to the CRC heredity.

METHODS

The cross-sectional study observed 71 respondents from May 2018 to December 2019 in determining the CRC hereditary status through MSH2 mRNA expression using reverse transcription-polymerase chain reaction and the disease’s risk factors. Data were analyzed through Chi-Square, Fischer exact, t-test, Mann-Whitney, and multiple logistics.

RESULTS

There are significant differences of MSH2 within CRC group among tissue and blood; yet, negative for significance between groups. Through the blood gene expression fifth percentile, the hereditary CRC cut-off is 11059 fc, dividing the 40 CRC respondents to 32.5% with hereditary CRC. Significant risk factors include age, family history, and staging. Nonetheless, after multivariate control, age is just a confounder. Further, the study develops a probability equation with area under the curve 82.2%.

CONCLUSION

Numerous factors have significant relations to heredity of CRC patients. However, true important factors are staging and family history, while age and others are confounders. The study also established a definite cut-off point for heredity CRC based on mRNA MSH2 expression, 11059 fc. These findings shall act as concrete foundations on further risk factors and/or genetical CRC future studies.

Keywords: Colorectal cancer; MSH2 gene; Non-modifiable factors; Risk probability

Core Tip: The study has determined a definitive cut-off for grouping colorectal cancer (CRC) with its heredity using the MSH2 mRNA gene expression, which amounts to 11059 fc. The gene expressions may differ between blood and tissue sample of the CRC group, yet none between CRC and control group. Nevertheless, subsequent risk factors of family history and staging are found to be significant toward the heredity. The after-mentioned risk factors act as urgent reminder for highly risky people with family history of CRC and/or high CRC staging to have themselves and their immediate family members to undergo routine examinations as well as strict preventions.