Utility of KRAS Gene and Clinicopathological Features in the Assessment of the Risk of Type 2 Diabetes in the Etiology of Colon Cancer

Abstract

Background Cancer and diabetes have a tremendous impact on health globally. This study aimed to evaluate the KRAS gene in colon cancer tissues obtained from patients with type 2 diabetes mellitus (T2DM).
Materials and Methods Data from 315 cases (156 colon diabetics and 159 patients were nondiabetics) were retrospectively retrieved. mRNA from surgically resected colon cancer tumors were also retrieved.
Results The expression of KRAS mRNA was significantly higher in patients afflicted with T2DM than nondiabetic patients. The KRAS mRNA levels were significantly amplified from primary to metastatic lesions (p < 0.001).
Conclusion The association between T2DM and colon cancer was well-established in the present study.

Keywords

colon cancer / KRAS / gene expression / immunohistochemistry / type 2 diabetes

Ethical Approval

The study was approved by the Ethical Committee at the College of Medicine, University of Hail under the protocol, “EC-00053.”

Funding

This study was funded by the researchers Supporting Project number (RSP-2019/111), King Saud University, Riyadh, Saudi Arabia.

Conflict of Interest

None declared.

References

[1] Suh S, Kim KW. Diabetes and cancer: is diabetes causally related to cancer?. Diabetes Metab J 2011; 35(03): 193-198

[2] Law PJ, Timofeeva M, Fernandez-Rozadilla C, et al; PRACTICAL consortium. Association analyses identify 31 new risk loci for colorectal cancer susceptibility. Nat Commun 2019; 10(01): 2154

[3] Soltani G, Poursheikhani A, Yassi M, Hayatbakhsh A, Kerachian M, Kerachian MA. Obesity, diabetes and the risk of colorectal adenoma and cancer. BMC Endocr Disord 2019; 19(01): 113

[4] Chireh B, D'Arcy C. Shared and unique risk factors for depression and diabetes mellitus in a longitudinal study, implications for prevention: an analysis of a longitudinal population sample aged ⩾ 45 years. Ther Adv Endocrinol Metab 2019

[5] (e-pub ahead of print). DOI: 10.1177/2042018819865828.

[6] Luo J, Lin HC, He K, Hendryx M. Diabetes and prognosis in older persons with colorectal cancer. Br J Cancer 2014; 110(07): 1847-1854

[7] Huang YC, Lin JK, Chen WS, et al. Diabetes mellitus negatively impacts survival of patients with colon cancer, particularly in stage II disease. J Cancer Res Clin Oncol 2011; 137(02): 211-220

[8] Berster JM, Göke B. Type 2 diabetes mellitus as risk factor for colorectal cancer. Arch Physiol Biochem 2008; 114(01): 84-98

[9] Arrington AK, Heinrich EL, Lee W, et al. Prognostic and predictive roles of KRAS mutation in colorectal cancer. Int J Mol Sci 2012; 13(10): 12153-12168

[10] Stephens RM, Yi M, Kessing B, Nissley DV, McCormick F. Tumor RAS gene expression levels are influenced by the mutational status of RAS genes and both upstream and downstream RAS pathway genes. Cancer Inform 2017

[11] (e-pub ahead of print). DOI: 10.1177/1176935117711944.

[12] Yang IS, Kim S. Isoform specific gene expression analysis of KRAS in the prognosis of lung adenocarcinoma patients. BMC Bioinformatics 2018; 19(Suppl. 01): 40

[13] Cicenas J, Tamosaitis L, Kvederaviciute K, et al. KRAS, NRAS and BRAF mutations in colorectal cancer and melanoma. Med Oncol 2017; 34(02): 26

[14] Misale S, Yaeger R, Hobor S, et al. Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer. Nature 2012; 486(7404): 532-536

[15] Aldiab A, Al Khayal KA, Al Obaid OA, et al. Clinicopathological features and predictive factors for colorectal cancer outcome in the Kingdom of Saudi Arabia. Oncology 2017; 92(02): 75-86

[16] Hobbs GA, Der CJ, Rossman KL. RAS isoforms and mutations in cancer at a glance. J Cell Sci 2016; 129(07): 1287-1292

[17] Jarvandi S, Davidson NO, Schootman M. Increased risk of colorectal cancer in type 2 diabetes is independent of diet quality. PLoS One 2013; 8(09): e74616

[18] Miłek T, Forysiński K, Myrcha P, Ciostek P. Diabetes association of polyps and colon cancer. Pol Przegl Chir 2019; 91(04): 9-12

[19] Laish I, Mizrahi J, Naftali T, Konikoff FM. Diabetes mellitus and age are risk factors of interval colon cancer: a case-control study. Dig Dis 2019; 37(04): 291-296

[20] Noh GY, Hwang DY, Choi YH, Lee YY. Effect of diabetes mellitus on outcomes of colorectal cancer. J Korean Soc Coloproctol 2010; 26(06): 424-428

[21] Slattery ML, Pellatt DF, Mullany LE, Wolff RK, Herrick JS. Gene expression in colon cancer: A focus on tumor site and molecular phenotype. Genes Chromosomes Cancer 2015; 54(09): 527-541

[22] Kheirelseid EA, Miller N, Chang KH, Nugent M, Kerin MJ. Clinical applications of gene expression in colorectal cancer. J Gastrointest Oncol 2013; 4(02): 144-157

[23] Liang H, Zhang J, Shao C, et al. Differential expression of RBM5, EGFR and KRAS mRNA and protein in non-small cell lung cancer tissues. J Exp Clin Cancer Res 2012; 31(01): 36

[24] Yuhara H, Steinmaus C, Cohen SE, Corley DA, Tei Y, Buffler PA. Is diabetes mellitus an independent risk factor for colon cancer and rectal cancer?. Am J Gastroenterol 2011; 106 (11) 1911-1921 , quiz 1922

[25] Imamura Y, Lochhead P, Yamauchi M, et al. Analyses of clinicopathological, molecular, and prognostic associations of KRAS codon 61 and codon 146 mutations in colorectal cancer: cohort study and literature review. Mol Cancer 2014; 13: 135

[26] Dahabreh IJ, Terasawa T, Castaldi PJ, Trikalinos TA. Systematic review: Anti-epidermal growth factor receptor treatment effect modification by KRAS mutations in advanced colorectal cancer. Ann Intern Med 2011; 154(01): 37-49

[27] Google Scholar

[28] Johnson DS, Cinnioglu C, Ross R, et al. Comprehensive analysis of karyotypic mosaicism between trophectoderm and inner cell mass. Molecular human reproduction 2010; 16(12): 944-949

RIGHTS & PERMISSIONS

Global Medical Genetics