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
ARTICLE HIGHLIGHTS
Research background

The lack of golden standard for categorizing hereditary status of colorectal cancer (CRC) poses diagnostic and management problems. Identifying proper techniques is urgent to procure the best care, prevention, risk factors management, and treatment of CRC be it hereditary or sporadic, along with judicious resource consumption.

Research motivation

The lack of golden standard leaves a gaping hole in the LS CRC healthcare system. Previous guideline of Bethesda and Amsterdam have tried yet fail in the applicability area especially with later age onset and smaller family. These coupled with the hazardous nature of CRC or lynch syndrome and scarce information on CRC risk factors identifications motivate the authors to commence the present study.

Research objectives

To determine the gold standard cut-off of MSH2 gene expression for hereditary cluster as well as to identify and examine the relationship of hereditary non-polyposis colon cancer (HNPCC) with its non-modifiable risk factors.

Research methods

Consecutive sampling of the hospital internal medicine patients with CRC provides the case group. Then, the control group was concocted by matching the characteristics of the case group. MSH2 mRNA was then analyzed through blood and tissue collection and reverse transcription-polymerase chain reaction. Further, the gene expression cut-off determined using percentile technique akin to Cauchy distribution of M, C, A, and D circular data statistics. CRC groups then clustered into hereditary and sporadic according to the MSH2 gene expression against the cut-off. Lastly, risk factors are contrasted between each cluster and developed into a prediction model.

Research results

In a group of 40 CRCs differentiated into 13 hereditary and 27 sporadic through MSH2 mRNA cut-off in 11059 fc, significant risk factors for the hereditary CRC are family history and staging with (OR: 22.784, 95%CI: 2.423-214.273, P = 0.006; OR: 10.970, 95%CI: 1.199-100.382, P = 0.034). Moreover, a prediction model is concocted with area under the curve 82.2%.

Research conclusions

The cut-off of MSH2 mRNA 5th percentile provided rough clustering of hereditary and sporadic CRC groups. Significant risk factors toward HNPCC are family history and staging, while age is just a confounder.

Research perspectives

Future research directions include validation of the determined cut-off and reliability testing of the risk factors in a bigger sample size and/or with the general population. Further, a longitudinal study on the risk factors effects should be evaluated.