SIGNIFICANT FACTORS ASSOCIATED WITH INSULIN-LIKE GROWTH FACTOR 1 AND ITS BINDING PROTEIN 3 IN COLORECTAL CANCER – MULTIPLE REGRESSION ANALYSIS
DOI:
https://doi.org/10.52340/jd.2022.06.18Abstract
Aim: the aim of our study was to investigate the association of insulin-like growth factor-1 and its binding protein 3 levels with CRC risk factors and symptoms by multiple regression analyzes.
Methods: The IGF-1 laboratory test was performed using the ECLIA method. Serum insulin and glucose levels were assessed by oral glucose tolerance test (OGTT) in fasting state and after 120 minutes of glucose loading (40 g / 1 m2 of body surface). Multiple regression analysis performed to study the mutual impact of different parameters on outcome (IGF-1 and IGF BP3).
Results: Finally, significant variables (factors) were left in the model having mutual effect on the outcome (IGF BP3 value). The linear multiple regression function took the following form: Hence these factors (each factor in parentheses indicates the nature of the correlation - direct or inverse): X1 - Sex (direct); X4 – Code of Surgery (inverse); X7 – other general pains/symptoms (inverse); X13 - Flatulence Gases (inverse); X14 - Diarrhea (direct); X20 – A course of chemotherapy or radiation therapy before surgery (inverse); X27 – HOMA-S (direct); X28 - HOMA-IR (inverse); X31 – creatinine (direct).
Conclusion: Based on the results of current study we concluded that CRC is multifactorial and many significant factors are responsible for its development. One of possible mechanisms for its development is the changes insulin/IGF-1 signaling pathway with other significant biological and non-biological factors.
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Siegel RL, Miller KD, Goding Sauer A, Fedewa SA, Butterly LF, Anderson JC et al. Colorectal cancer statistics, 2020. CA Cancer J Clin. 2020; 70:145–164.
International Agency for Research on Cancer (IARC) Global Cancer Observatory (GLOBOCAN) IARC; Lyon: 2018.
Cancer in Georgia 2015-2019. National Center for Disease Control and Public Health of Georgia. Official Bulletin of NCDC, 2020; Tbilisi, Georgia.
Gao Y, Katki H, Graubard B, Pollak M, Martin M, Tao Y et al. Serum IGF1, IGF2 and IGFBP3 and risk of advanced colorectal adenoma. Int. J. Cancer. 2012; 131:E105–E113.
Jiang B, Zhang X, Du LL, Wang Y, Liu DB, Han CZ et al. Possible roles of insulin, IGF-1 and IGFBPs in initiation and progression of colorectal cancer. World J. Gastroenterol. 2014; 20:1608–1613.
Kasprzak A, Szaflarski W. Role of Alternatively Spliced Messenger RNA (mRNA) Isoforms of the Insulin-Like Growth Factor 1 (IGF1) in Selected Human Tumors. Int. J. Mol. Sci. 2020; 21:6995.
Aguirre GA, de Ita JR., de la Garza RG, Castilla-Cortazar I. Insulin-like growth factor-1 deficiency and metabolic syndrome. J. Transl. Med. 2016; 14:3.
Jasperson KW, Tuohy TM, Neklason DW, Burt RW. Hereditary and familial colon cancer. Gastroenterology. 2010; 138:2044–2058.
Murphy N, Ward HA, Jenab M, Rothwell JA, Boutron-Ruault MC, Carbonnel F et al. Heterogeneity of colorectal cancer risk factors by anatomical subsite in 10 European countries: A multinational cohort study. Clin Gastroenterol Hepatol. 2019; 17:1323–1331.e6.
Renehan AG, Tyson M, Egger M, Heller RF, Zwahlen M. Body-mass index and incidence of cancer: A systematic review and meta-analysis of prospective observational studies. Lancet. 2008; 371:569–578.
Dong Y, Zhou J, Zhu Y, Luo L, He T, Hu H et al. Abdominal obesity and colorectal cancer risk: Systematic review and meta-analysis of prospective studies. Biosci Rep. 2017; 37:BSR20170945.
Johnson CM, Wei C, Ensor JE, Smolenski DJ, Amos CI, Levin B, Berry DA. Meta-analyses of colorectal cancer risk factors. Cancer Causes Control. 2013; 24:1207–1222.
Zisman AL, Nickolov A, Brand RE, Gorchow A, Roy HK. Associations between the age at diagnosis and location of colorectal cancer and the use of alcohol and tobacco: Implications for screening. Arch Intern Med. 2006; 166:629–34.
Limburg PJ, Stolzenberg-Solomon RZ, Vierkant RA, Roberts K, Sellers TA, Taylor PR et al. Insulin, glucose, insulin resistance, and incident colorectal cancer in male smokers. Clin. Gastroenterol. Hepatol. 2006; 4:1514–1521.
Gunter MJ, Hoover DR, Yu H, Wassertheil-Smoller S, Rohan TE, Manson JE et al. Insulin, insulin-like growth factor-I, endogenous estradiol, and risk of colorectal cancer in postmenopausal women. Cancer Res. 2008; 68:329–337.
Kabat GC, Kim MY, Strickler HD, Shikany JM, Lane D, Luo J et al. A longitudinal study of serum insulin and glucose levels in relation to colorectal cancer risk among postmenopausal women. Br. J. Cancer. 2012; 106:227–232.
Vulcan A, Manjer J, Ohlsson B. High blood glucose levels are associated with higher risk of colon cancer in men: A cohort study. BMC Cancer. 2017; 17:842.
Xu J, Ye Y, Wu H, Duerksen-Hughes P, Zhang H, Li P et al. Association between markers of glucose metabolism and risk of colorectal cancer. BMJ Open. 2016; 6:e011430.
De Pergola G., Silvestris F. Obesity as a major risk factor for cancer. J. Obes. 2013:291546.
Hong H, Cui ZZ, Zhu L, Fu SP, Rossi M, Cui YH, Zhu BM. Central IGF1 improves glucose tolerance and insulin sensitivity in mice. Nutr. Diabetes. 2017; 7:2.
Wallace TM, Levy JC, Matthews DR. Use and abuse of HOMA modeling. Diabetes Care. 2004; 27(6):1487-95.
Graff RE, Möller S, Passarelli MN, Witte JS, Skytthe A, Christensen K et al. Familial risk and heritability of colorectal cancer in the nordic twin study of cancer. Clin Gastroenterol Hepatol. 2017; 15:1256-1264.
Lichtenstein P, Holm NV, Verkasalo PK, Iliadou A, Kaprio J, Koskenvuo M et al. Environmental and heritable factors in the causation of cancer-analyses of cohorts of twins from Sweden, Denmark, and Finland. N Engl J Med. 2000; 343:78–85.
Fleming M, Ravula S, Tatishchev SF, Wang HL. Colorectal carcinoma: Pathologic aspects. J Gastrointest Oncol. 2012; 3:153–173.
Low EE, Demb J, Liu L, Earles A, Bustamante R, Williams CD et al. Risk factors for early-onset colorectal cancer. Gastroenterology. 2020; 159:492–501.e7.
Liu PH, Wu K, Ng K, Zauber AG, Nguyen LH, Song M et al. Association of obesity with risk of early-onset colorectal cancer among women. JAMA Oncol. 2019; 5:37–44.
Nelson DE, Jarman DW, Rehm J, Greenfield TK, Rey G, Kerr WC et al. Alcohol-attributable cancer deaths and years of potential life lost in the United States. Am J Public Health. 2013; 103:641–648.
Butler LM, Sinha R, Millikan RC, Martin CF, Newman B, Gammon MD et al. Heterocyclic amines, meat intake, and association with colon cancer in a population-based study. Am J Epidemiol. 2003; 157:434–445.
Kampman E, Slattery ML, Bigler J, Leppert M, Samowitz W, Caan BJ, Potter JD. Meat consumption, genetic susceptibility, and colon cancer risk: A United States multicenter case-control study. Cancer Epidemiol Biomarkers Prev. 1999; 8:15–24.
Santarelli RL, Pierre F, Corpet DE. Processed meat and colorectal cancer: A review of epidemiologic and experimental evidence. Nutr Cancer. 2008; 60:131–144.
Kabat GC, Miller AB, Jain M, Rohan TE. A cohort study of dietary iron and heme iron intake and risk of colorectal cancer in women. Br J Cancer. 2007; 97:118–122.
Sinha R. An epidemiologic approach to studying heterocyclic amines. Mutat Res. 2002; 506-507:197–204.
Pietinen P, Malila N, Virtanen M, Hartman TJ, Tangrea JA, Albanes D, Virtamo J. Diet and risk of colorectal cancer in a cohort of Finnish men. Cancer Causes Control. 1999; 10:387–396.
Terry P, Giovannucci E, Michels KB, Bergkvist L, Hansen H, Holmberg L, Wolk A. Fruit, vegetables, dietary fiber, and risk of colorectal cancer. J Natl Cancer Inst. 2001; 93:525–533.
Bardou M, Barkun AN, Martel M. Obesity and colorectal cancer. Gut. 2013; 62:933–947.
Kelly DM, Jones TH. Testosterone and obesity. Obes Rev. 2015; 16:581–606.
Matsuo K, Mizoue T, Tanaka K, Tsuji I, Sugawara Y, Sasazuki S et al. Association between body mass index and the colorectal cancer risk in Japan: Pooled analysis of population-based cohort studies in Japan. Ann Oncol. 2012; 23:479–490.
Goh LY, Goh KL. Obesity: An epidemiological perspective from Asia and its relationship to gastrointestinal and liver cancers. J Gastroenterol Hepatol. 2013; 28(Suppl 4):S54–S58.
World Cancer Research Fund Continuous update project report. Food, nutrition, physical activity, and the prevention of colorectal cancer. WCRF/AICR; 2011.
Song M, Hu FB, Spiegelman D, Chan AT, Wu K, Ogino S et al. Long-term status and change of body fat distribution, and risk of colorectal cancer: A prospective cohort study. Int J Epidemiol. 2016; 45:871–883.
Moore LL, Bradlee ML, Singer MR, Splansky GL, Proctor MH, Ellison RC, Kreger BE. BMI and waist circumference as predictors of lifetime colon cancer risk in Framingham study adults. Int J Obes Relat Metab Disord. 2004; 28:559–567.
Samaras K, Botelho NK, Chisholm DJ, Lord RV. Subcutaneous and visceral adipose tissue gene expression of serum adipokines that predict type 2 diabetes. Obesity (Silver Spring) 2010; 18:884–889. doi:10.1038/oby.2009.443.
Lim U, Ernst T, Buchthal SD, Latch M, Albright CL, Wilkens LR et al. Asian women have greater abdominal and visceral adiposity than Caucasian women with similar body mass index. Nutr Diabetes. 2011; 1:e6.
Ma Y, Yang Y, Wang F, Zhang P, Shi C, Zou Y, Qin H. Obesity and risk of colorectal cancer: A systematic review of prospective studies. PLoS One. 2013; 8:e53916.
Lee YJ, Myung SK, Cho B, Park BJ, Park JH, Ju W et al. Adiposity and the risk of colorectal adenomatous polyps: A meta-analysis. Cancer Causes Control. 2011; 22:1021–1035.
Guraya SY. Association of type 2 diabetes mellitus and the risk of colorectal cancer: A meta-analysis and systematic review. World J Gastroenterol. 2015; 21:6026–6031.
Kahn SE, Hull RL, Utzschneider KM. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature. 2006; 444:840–846.
Moller DE, Flier JS. Insulin resistance-mechanisms, syndromes, and implications. N Engl J Med. 1991; 325:938–948.
Pollak M. Insulin and insulin-like growth factor signalling in neoplasia. Nat Rev Cancer. 2008; 8:915–928.
Calle EE, Kaaks R. Overweight, obesity and cancer: Epidemiological evidence and proposed mechanisms. Nat Rev Cancer. 2004; 4:579–591.
Murphy N, Strickler HD, Stanczyk FZ, Xue X, Wassertheil-Smoller S, Rohan TE et al. A prospective evaluation of endogenous sex hormone levels and colorectal cancer risk in postmenopausal women. J Natl Cancer Inst. 2015; 107:djv210.
Hetemäki N, Savolainen-Peltonen H, Tikkanen MJ, Wang F, Paatela H, Hämäläinen E et al. Estrogen metabolism in abdominal subcutaneous and visceral adipose tissue in postmenopausal women. J Clin Endocrinol Metab. 2017; 102:4588–4595.
Keum N, Giovannucci E. Global burden of colorectal cancer: Emerging trends, risk factors and prevention strategies. Nat Rev Gastroenterol Hepatol. 2019; 16:713–732.
Hofseth LJ, Hebert JR, Chanda A, Chen H, Love BL, Pena MM et al. Early-onset colorectal cancer: Initial clues and current views. Nat Rev Gastroenterol Hepatol. 2020; 17:352–364.
Burkitt DP. Epidemiology of cancer of the colon and rectum. Cancer. 1971; 28:3–13.
Aune D, Chan DS, Lau R, Vieira R, Greenwood DC, Kampman E, Norat T. Dietary fibre, whole grains, and risk of colorectal cancer: Systematic review and dose-response meta-analysis of prospective studies. BMJ. 2011; 343:d6617.
World Cancer Research Fund Diet, nutrition, physical activity and cancer: A global perspective: A summary of the third expert report. World Cancer Research Fund International. 2018.
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