Levels of interleukin-2 in patients with colon cancer and diabetes type 2
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Department of Internal Diseases, Diabetology and Endocrinology, Warsaw Medical University, Poland
J Pre Clin Clin Res. 2016;10(1):1–5
Introduction and objective:
The risk of development colon cancer (CC) is increased significantly among patients with the type 2 diabetes (T2DM). A mechanism responsible for the higher prevalence of CC among diabetic patients may be associated with the immunity system. The aim of this study is to point out the differences in the immunity state in terms of interleukin 2 level among patients with T2DM suffering from CC, and patients without these diseases

Material and Methods:
79 patients were included the tests, divided into 4 groups: Group 1–23 people with T2DM, Group 2–23 people with large intestine CC, Group 3–10 people with large CC and T2DM, and Group 4–23 people without T2DM or CC. Each patient had a colonoscopy and those with cancer were confirmed in a histopathological examination. Laboratory measurements included fasting glucose, insulin, C-peptide. The concentration of interleukin-2 in serum was determined with the immunoenzymatic (ELISA) method.

The results obtained showed that in patients with T2DM and CC the concentration of interleukin-2 was statistically higher than in the other groups.(4.21±1.61 pg/ml vs. Group 1 -1.64±0.44 pg/ml, Group 2–1.54±0.21 pg/ml, and Group 4–1.70±0.36 pg/ml; p<0.05). Insulin levels, C-peptide and HOMA-IR did not differ significantly between groups, but a tendency was observed to higher values of HOMA-IR and insulin levels in the groups with T2DM alone and T2DM with concomitant CC.

The data show differences in the immunity state of patients with T2DM and CC, compared with people without those two diseases. Elevated level of interleukin 2 found in this group, after confirmation in other studies with more patients, could be used as a marker of an increased risk of CC in people with T2DM

Zdrojewski T, Rutkowski M, Bandosz P, Gaciong Z, Jędrzejczyk T, Solnica B, et al. Prevalence and control of cardiovascular risk factors in Poland. Assumptions and objectives of the NATPOL 2011 Survey. Kardiol Pol. 2013; 71(4): 381–392.
Jeong Hwan Kim, et al. Is Metabolic Syndrome A Risk Factor For Colorectal Adenoma? Cancer Epidemiol Biomarkers Prev. 2007; 16(8): 1543–1546.
Tomas NM, Masur K, Piecha JC, Niggemann B, Zänker KS. Akt and phospholipase CY are involved in the regulation of growth and migration of MDA-MB-468 breast cancer and SW480 colon cancer cells when cultured with diabetogenic levels of glucose and insulin. BMC Research Notes. 2012; 10(5): 214.
Hsieh MC, Lee TC, Cheng SM, Tu ST, Yen MH, Tseng CH, et al. The influence of type 2 diabetes and glucose-lowering therapies on cancer risk in the Taiwanese. Exp Diabetes Res. 2012; 2012:413788.
Lynch LA, O`Connell JM, Kwasnik AK, Cawood TJ, O1Farrelly C, O`Shea DB. Are natural killer cells protecting the metabolically healthy obese patient? Obesity (silver Spring) 2009; 17(3): 601–605.
Lin YC (1), Mahalingam J, Chiang JM, Su PJ, Chu YY, Lai HY, Fang JH, Huang CT, Chiu CT, Lin CY. Activated but not resting regulatory T cells accumulated in tumor microenvironment and correlated with tumor progression in patients with colorectal cancer. Int J Cancer. 2013; 15;132(6): 1341–1350.
Larsson SC, Orsini N, Wolk A, diabetes mellitus and risk of colorectal dancer: A Meta-Analysis. J Natl Cancer Inst. 2005; 97(22): 1679–1687.
Yuhara H, Steinmaus C, Cohen SE, Corley DA, Tei Y, Buffler P., Is diabetes mellitus an independent risk factor for colon cancer and rectal cancer? Am J Gastroenterol. 2011; 106 (11): 1911–1922.
He J, Stram DO, Kolonel LN, Henderson BE, Le Marchand L, Haiman CA. The association of diabetes with colorectal cancer risk: the Multiethnic Cohort. Br J Cancer. 2010; 103(1): 120–126.
De Bruijn KM, Arends LR, Hansen BE, Leeflang S, Ruiter R, van Eijck CH. Systematic review and meta-analysis of the association between diabetes mellitus and incidence and mortality in breast and colorectal cancer. Br J Surg Soc. 2013; 100(11): 1421–1429.
Giovaucci E. Metabolic syndrome, hiperinsulinemia and colon cancer: a review. Am J Clin Nutr. 2007; 86(3): 836–842.
P. Piątkiewicz. Patogeneza zwiększonej częstości występowania nowotworów złośliwych u osób z cukrzycą. Med Metab. 2011; 15(3): 15–19.
Brunner EJ, Kivimäki M, Witte DR, Lawlor DA, Davey Smith G, Cooper JA, Miller M, et al. Inflammation, Insulin Resistance and Diabetes – Mendelian randomization using CRP haplotypes points upstream. PLoS Med. 2008; 12: 5(8).
Yaturu S, Rains J, Jain SK. Relationship of elevated osteoprotegerin with insulin resistance, CRP, and TNF-alpha levels in men with type 2 diabetes. Cytokine. 2008; 44(1): 168–171.
Schloot NC, Hanifi-Moghaddam P, Goebel C, Shatavi SV, Flohe S, et al. Serum INF-gamma and IL-10 levels are associated with disease progression in non-obese diabetic mice. Diabetes Metab Res Rev. 2002; 18(1): 64–70.
Kim S, Keku TO, Martin C, Galanko J, Woosley JT, Schroeder JC, Satia JA, et al. Circulating levels of inflammatory cytokines and risk of colorectal adenomas. Cancer Res. 2008; 68: 323–328.
Sasaki Y, Takeda H, Sato T, Orii T, Nishise S, Nagino K, Iwano D, et al. Serum interleukin-6, insulin and HOMA-IR in male individuals with colorectal adenoma. Clin Cancer Res. 2012; 18(2): 392–399.
Day SD, Enos RT, McClellan JL, Steiner JL, Velázquez KT, Murphy EA. Linking inflammation to tumorigenesis in a mouse model of high-fat-diet-enhanced colon cancer. Cytokine. 2013; 64(1): 454–462.
Zhu M, Zhu Y, Lance P. TNF-α-activated stromal COX-2 signalling promotes proliferative and invasive potential of colon cancer epithelial cells. Cell Prolif. 2013; 46(4): 374–381.
Putoczki TL, Thiem S, Loving A, Busuttil RA, Wilson NJ, et al. Interleukin -11 is the dominant IL-6 family cytokine during gastrointestinal tumorigenesis and can be targeted therapeutically. Cancer Cell. 2013; 12; 24(2): 257–271.
Prieto-Hontoria PL, Pèrez-Matute P, Fernandez-Galilea M, Bustosz M, Martinez JA, Moreno-Aliaga MJ. Role of obesity-associated dysfunctional adipose tissue in cancer: A molecular nutrition approach. Biochim Biophys Acta. 2011; 1807(6): 664–678.
LeRoith D, Novoyadly R, Gallgher EJ, Lann D, Vijayakumar A, Yakar S. Obesity and type 2 diabetes are associated with an increased risk of developing cancer and a worse prognosis; epidemiological and mechanistic evidence. Exp Clin Endocrinol Diabetes. 2008; 116 (Suppl 1): S1–3.
Marszałek A, Szylberg L, Wiśniewska E, Janiczek M. Impact of COX-2, IL-1β, TNF-α, IL-4 and IL-10 on the process of carcinogenesis in the large bowel. Pol J Pathol. 2012; 63(4): 221–227.
Setia S, Nehru B, Sanyal SN. Activation of NF-kB: Bridging the gap between inflammation and cancer in colitis-mediated colon carcinogenesis. Biomed Pharmacother. 2014; 68(1): 119–128.
Jakub Gołąb, Marek Jakóbisiak, Witold Lasek, Tomasz Stokłosa. Immunologia. Nowe Wydanie. Wydawnictwo Naukowe PWN SA, Warszawa 2014 p.134, 135, 163–165.
Tae HK, Chin-Ping M, LIangmeiH, Ya-Chea T, Katherine L,et al. Tumor-targeted delivery of IL-2 by NKG2D leads to accumulation of antygen-specific CD8+ T cells in the tumor loci and enhanced anty-tumor effects. PLoS One. 2012; 7(4): e35141.
Zhang Y, Morgan R, Podack ER, Rosenblatt J. B cell regulation of anti-tumor immune response. Immunol Res. 2013; 57(1–3): 115–124.
Svensson H, Olofsson V, Lundin S, Yakkala C, Björck S, Börjesson L, Gustavsson B, Quiding-Järbrink M. Accumulation of CCR4+CTLA-4 FOXP3+CD25(hi) regulatory T cells in colon adenocarcinomas correlate to reduced activation of conventional T cells. PLoS One.2012; 7(2).