Microsatellite Instability is Inversely Associated with Type 2 Diabetes Mellitus in Colorectal Cancer

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2019 Apr 20

PMID 31002690

Citations 6

Authors

Yujiro Nakayama

Takeru Iijima

Rika Wakaume

Keiichi Takahashi

Hiroshi Matsumoto

Daisuke Nakano

Michiko Miyaki

Tatsuro Yamaguchi

Affiliations

Soon will be listed here.

Abstract

Background: Microsatellite instability (MSI) is a clonal change in the number of repeated DNA nucleotide units in microsatellites. High-frequency MSI (MSI-H) colorectal cancers (CRCs) are known to have different clinicopathological features compared with microsatellite stable (MSS) CRCs. In addition, previous studies have shown that type2 diabetes mellitus (T2DM) is a risk factor for malignant tumors including CRCs. The aim of this study was to investigate the relationship between T2DM and MSI-H colorectal cancer.

Methods: The study design is a single center, cross-sectional study. Data from a series of 936 patients with CRCs were collected and MSI status was assessed.

Results: In total, 29 (3.1%) and 907 (96.9%) tumors were classified as having MSI-H and low-frequency microsatellite instability or being MSS (MSS), respectively. Of the 936 patients, 275 (29.6%) were associated with T2DM. One (3.4%) of the 29 MSI-H patients and 274 (30.2%) of the 907 MSS patients had T2DM. Thus, the incidence of T2DM was significantly less frequent in MSI-H compared with MSS patients (Fisher's exact test: p = 0.0007).

Conclusions: We conclude that MSS tumors are significantly more common than MSI-H tumors among individuals with T2DM.

Citing Articles

Type 2 diabetes mellitus and post-colonoscopy colorectal cancer: clinical and molecular characteristics and survival.

Boysen M, Troelsen F, Sorensen H, Erichsen R Cancer Causes Control. 2024; 35(7):1043-1052.

PMID: 38483686 PMC: 11217032. DOI: 10.1007/s10552-024-01861-9.

Genomic instability genes in lung and colon adenocarcinoma indicate organ specificity of transcriptomic impact on Copy Number Alterations.

Rao C, Xu C, Zhang Y, Asch A, Yamada H Sci Rep. 2022; 12(1):11739.

PMID: 35817785 PMC: 9273645. DOI: 10.1038/s41598-022-15692-8.

Whole Exome Sequencing Identifies Two Novel Mutations in a Patient with UC Associated with PSC and SSA.

Wu D, Chen D, Shi W, Liu W, Zhou W, Qian J Can J Gastroenterol Hepatol. 2021; 2021:9936932.

PMID: 34545326 PMC: 8449715. DOI: 10.1155/2021/9936932.

Serum Tumor Markers Combined With Clinicopathological Characteristics for Predicting MMR and KRAS Status in 2279 Chinese Colorectal Cancer Patients: A Retrospective Analysis.

Zhao N, Cao Y, Yang J, Li H, Wu K, Wang J Front Oncol. 2021; 11:582244.

PMID: 34221952 PMC: 8247475. DOI: 10.3389/fonc.2021.582244.

Assessment of the Circulating Tumor Cells and Microsatellite Instability in Colorectal Cancer Patients: Prognostic and Diagnostic Value.

Alsayed A, Salem S, El Serafi M, Abdellateif M, Zekri A, Mohanad M Onco Targets Ther. 2021; 14:1937-1951.

PMID: 33758513 PMC: 7981167. DOI: 10.2147/OTT.S292551.

References

Jarvandi S, Davidson N, Schootman M . Increased risk of colorectal cancer in type 2 diabetes is independent of diet quality. PLoS One. 2013; 8(9):e74616. PMC: 3771921. DOI: 10.1371/journal.pone.0074616. View

Fung T, Schulze M, Manson J, Willett W, Hu F . Dietary patterns, meat intake, and the risk of type 2 diabetes in women. Arch Intern Med. 2004; 164(20):2235-40. DOI: 10.1001/archinte.164.20.2235. View

Rampino N, Yamamoto H, Ionov Y, Li Y, Sawai H, Reed J . Somatic frameshift mutations in the BAX gene in colon cancers of the microsatellite mutator phenotype. Science. 1997; 275(5302):967-9. DOI: 10.1126/science.275.5302.967. View

Leach F, Nicolaides N, Papadopoulos N, Liu B, Jen J, Parsons R . Mutations of a mutS homolog in hereditary nonpolyposis colorectal cancer. Cell. 1993; 75(6):1215-25. DOI: 10.1016/0092-8674(93)90330-s. View

Jiang Y, Ben Q, Shen H, Lu W, Zhang Y, Zhu J . Diabetes mellitus and incidence and mortality of colorectal cancer: a systematic review and meta-analysis of cohort studies. Eur J Epidemiol. 2011; 26(11):863-76. DOI: 10.1007/s10654-011-9617-y. View

Colangelo L, Gapstur S, Gann P, Dyer A, Liu K . Colorectal cancer mortality and factors related to the insulin resistance syndrome. Cancer Epidemiol Biomarkers Prev. 2002; 11(4):385-91. View

Giovannucci E . Modifiable risk factors for colon cancer. Gastroenterol Clin North Am. 2002; 31(4):925-43. DOI: 10.1016/s0889-8553(02)00057-2. View

Vogelstein B, Fearon E, Hamilton S, Kern S, Preisinger A, Leppert M . Genetic alterations during colorectal-tumor development. N Engl J Med. 1988; 319(9):525-32. DOI: 10.1056/NEJM198809013190901. View

Akiyama Y, Sato H, Yamada T, Nagasaki H, Tsuchiya A, Abe R . Germ-line mutation of the hMSH6/GTBP gene in an atypical hereditary nonpolyposis colorectal cancer kindred. Cancer Res. 1997; 57(18):3920-3. View

10.

Fishel R, Lescoe M, Rao M, Copeland N, Jenkins N, Garber J . The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer. Cell. 1993; 75(5):1027-38. DOI: 10.1016/0092-8674(93)90546-3. View

11.

Markowitz S, Wang J, Myeroff L, Parsons R, Sun L, Lutterbaugh J . Inactivation of the type II TGF-beta receptor in colon cancer cells with microsatellite instability. Science. 1995; 268(5215):1336-8. DOI: 10.1126/science.7761852. View

12.

Ma J, Pollak M, Giovannucci E, Chan J, Tao Y, Hennekens C . Prospective study of colorectal cancer risk in men and plasma levels of insulin-like growth factor (IGF)-I and IGF-binding protein-3. J Natl Cancer Inst. 1999; 91(7):620-5. DOI: 10.1093/jnci/91.7.620. View

13.

Pais R, Silaghi H, Silaghi A, Rusu M, Dumitrascu D . Metabolic syndrome and risk of subsequent colorectal cancer. World J Gastroenterol. 2009; 15(41):5141-8. PMC: 2773892. DOI: 10.3748/wjg.15.5141. View

14.

Konishi M, Tanaka K, Muraoka M, Onda A, Okumura Y, Kishi N . Molecular nature of colon tumors in hereditary nonpolyposis colon cancer, familial polyposis, and sporadic colon cancer. Gastroenterology. 1996; 111(2):307-17. DOI: 10.1053/gast.1996.v111.pm8690195. View

15.

Wang M, Hu R, Wu H, Pan J, Gong W, Guo L . Cancer risk among patients with type 2 diabetes mellitus: a population-based prospective study in China. Sci Rep. 2015; 5:11503. PMC: 4469976. DOI: 10.1038/srep11503. View

16.

Kim H, Jen J, Vogelstein B, Hamilton S . Clinical and pathological characteristics of sporadic colorectal carcinomas with DNA replication errors in microsatellite sequences. Am J Pathol. 1994; 145(1):148-56. PMC: 1887287. View

17.

van de Wetering M, Sancho E, Verweij C, de Lau W, Oving I, Hurlstone A . The beta-catenin/TCF-4 complex imposes a crypt progenitor phenotype on colorectal cancer cells. Cell. 2002; 111(2):241-50. DOI: 10.1016/s0092-8674(02)01014-0. View

18.

Hennessy B, Smith D, Ram P, Lu Y, Mills G . Exploiting the PI3K/AKT pathway for cancer drug discovery. Nat Rev Drug Discov. 2005; 4(12):988-1004. DOI: 10.1038/nrd1902. View

19.

Miyaki M, Konishi M, Tanaka K, Muraoka M, Yasuno M, Igari T . Germline mutation of MSH6 as the cause of hereditary nonpolyposis colorectal cancer. Nat Genet. 1997; 17(3):271-2. DOI: 10.1038/ng1197-271. View

20.

Shitoh K, Konishi F, Miyakura Y, Togashi K, Okamoto T, Nagai H . Microsatellite instability as a marker in predicting metachronous multiple colorectal carcinomas after surgery: a cohort-like study. Dis Colon Rectum. 2002; 45(3):329-33. DOI: 10.1007/s10350-004-6177-1. View