Evaluation of the relationship between glycemic parameters and preoperative tumor markers in colorectal, prostate, and breast cancers: Glycemic parameters and preoperative tumor markers

Alpaslan Öztürk; Nihal İnandıklıoğlu; Şener Balas; Ahmet Nihat Karakoyunlu

doi:10.5281/zenodo.8395853

Authors

Alpaslan Öztürk Ankara Etlik City Hospital, Department of Clinical Biochemistry, Ankara, Turkey https://orcid.org/0000-0003-4525-3477
Nihal İnandıklıoğlu Yozgat Bozok University Faculty of Medicine, Department of Medical Biology, Yozgat, Turkey https://orcid.org/0000-0001-7137-3929
Şener Balas Başkent University Faculty of Medicine, Department of General Surgery, Ankara, Turkey https://orcid.org/0000-0002-9154-3179
Ahmet Nihat Karakoyunlu Ankara Etlik City Hospital, Department of Urology, Ankara, Turkey https://orcid.org/0000-0002-6680-9860

DOI:

https://doi.org/10.5281/zenodo.8395853

Keywords:

Breast cancer, colorectal cancer, glucose, prostate cancer, tumor markers

Abstract

Objective: The basic metabolic processes of cancer cells involve growth and proliferation. These cells use glucose as the main source. We aimed to investigate the significance of glycemic parameters and preoperative tumor markers in terms of risk and stage of cancer development.

Methods: We employed a total of 400 participants, including 100 patients diagnosed with colorectal cancer, 100 patients diagnosed with prostate cancer, 100 patients diagnosed with breast cancer, and 100 healthy controls. We evaluated glucose, HbA1c, insulin, carbohydrate antigen 15-3 (CA15-3), carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 72-4 (CA72-4), carcinoembryonic antigen (CEA) and prostate specific antigen (PSA) results of these individuals.

Results: We found significantly higher levels of fasting plasma glucose (FPG) and fasting plasma insulin (FPI) in breast cancer patients; FPG, FPI, and HbA1c in prostate cancer patients; and FPG and HbA1c values in colorectal cancer patients compared to control groups (p<0.05). Furthermore, we found significantly higher CEA and CA15-3 in breast cancer patients; PSA, CEA, and CA19-9 in prostate cancer patients; and CEA, CA19-9, and CA72-4 in colorectal cancer patients compared to those in the control groups (p<0.05).

Conclusion: We confirmed the ability of glucose, insulin, and HbA1c to predict breast, prostate and colorectal cancer. In this context, the successful implementation of glycemic control and diabetes mellitus treatment in patients may enhance the efficacy of the treatment incertain cancers and reduce the incidence of the disease. However, more cohort studies are needed to demonstrate this relationship more clearly and to consider it a rule.

References

Pavlova NN, Zhu J, Thompson CB. The hallmarks of cancer metabolism: Still emerging. Cell Metab. 2022;34:355-77.

Nava GM, Madrigal Perez LA. Metabolic profile of the Warburg effect as a tool for molecular prognosis and diagnosis of cancer. Expert Rev Mol Diagn. 2022;22:439-47.

Zhong X, He X, Wang Y, Hu Z, Huang H, Zhao S, et al. Warburg effect in colorectal cancer: the emerging roles in tumor microenvironment and therapeutic implications. J Hematol Oncol. 2022;15:160.

Zhang M, Yang J, Jiang H, Jiang H, Wang Z. Correlation between glucose metabolism parameters derived from FDG and tumor TNM stages and metastasis-associated proteins in colorectal carcinoma patients. BMC Cancer. 2021;21:258-66.

Selvaraj S, Seidelmann SB, Soni M, Bhattaru A, Margulies KB, Shah SH, et al. Comprehensive nutrient consumption estimation and metabolic profiling during ketogenic diet and relationship with myocardial glucose uptake on FDG-PET. Eur Heart J. Cardiovasc Imaging. 2022;23:1690-7.

Wu J, He H, Zhang Q, Zhang Y. Fasting blood glucose was linearly associated with colorectal cancer risk in the population without self-reported diabetes mellitus history. Medicine (Baltimore). 2021;100:e26974.

Yang X, Ko GT, So WY, Ma RC, Yu LW, Kong AP, et al. Associations of hyperglycemia and insulin usage with the risk of cancer in type 2 diabetes: the Hong Kong diabetes registry. Diabetes. 2010;59:1254-60.

Buono G, Crispo A, Giuliano M, De Angelis C, Schettini F, Forestieri V, et al. Metabolic syndrome and early stage breast cancer outcome: results from a prospective observational study. Breast Cancer Res Treat. 2020;182:401-9.

Sousa AP, Costa R, Alves MG, Soares R, Baylina P, Fernandes R. The Impact of Metabolic Syndrome and Type 2 Diabetes Mellitus on Prostate Cancer. Front Cell Dev Biol. 2022;10:843458.

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.

Shang X, Song C, Du X, Shao H, Xu D, Wang X. The serum levels of tumor marker CA19-9, CEA, CA72-4, and NSE in type 2 diabetes without malignancy and the relations to the metabolic control. Saudi Med J. 2017;38:204-8.

Chen PC, Lin HD. Reversible high blood CEA and CA19-9 concentrations in a diabetic patient. Libyan J Med. 2012;7.

Bose S, Le A. Glucose Metabolism in Cancer. Adv Exp Med Biol. 2018;1063:3-12.

Hayes DF. Serum (circulating) tumor markers for breast cancer. Recent Results Cancer Res. 1996;140:101-13.

Duncan JL, Price A, Rogers K: The use of CA 15 -3 as a serum tumor marker in breast carcinoma. Eur J Cancer Clin Oncol. 1991;17:16–9.

O'Brien DP, Horgan PG, Gough DB, Skehill R, Grimes H, Given HF. CA15-3: a reliable indicator of metastatic bone disease in breast cancer patients. Ann R Coll Surg Engl. 1992;74:9-12.

Park BW, Oh JW, Kim JH, Park SH, Kim KS, Kim JH, et al. Preoperative CA 15-3 and CEA serum levels as predictor for breast cancer outcomes. Ann Oncol. 2008;19:675-81.

Novosyadlyy R, Lann DE, Vijayakumar A, Rowzee A, Lazzarino DA, Fierz Y, et al. Insulin-mediated acceleration of breast cancer development and progression in a nonobese model of type 2 diabetes. Cancer Res. 2010;70:741-51.

Goodwin PJ, Ennis M, Pritchard KI, Trudeau ME, Koo J, Madarnas Y, et al. Fasting insulin and outcome in early-stage breast cancer: results of a prospective cohort study. J Clin Oncol. 2002;20:42-51.

Miao Jonasson J, Cederholm J, Eliasson B, Zethelius B, Eeg-Olofsson K, Gudbjörnsdottir S. HbA1C and cancer risk in patients with type 2 diabetes--a nationwide population-based prospective cohort study in Sweden. PLoS One. 2012;7:e38784.

Lipscombe LL, Goodwin PJ, Zinman B, McLaughlin JR, Hux JE. Diabetes mellitus and breast cancer: a retrospective population-based cohort study. Breast Cancer Res Treat. 2006;98:349-56.

Kiwata JL, Dorff TB, Schroeder ET, Gross ME, Dieli-Conwright CM. A review of clinical effects associated with metabolic syndrome and exercise in prostate cancer patients. Prostate Cancer Prostatic Dis. 2016;19:323–32.

Gacci M, Russo GI, De Nunzio C, Sebastianelli A, Salvi M, Vignozzi L, et al. Meta-analysis of metabolic syndrome and prostate cancer. Prostate Cancer Prostatic Dis. 2017;20:146-55.

Cai H, Xu Z, Xu T, Yu B, Zou Q. Diabetes mellitus is associated with elevated risk of mortality among patients with prostate cancer: a meta-analysis of 11 cohort studies. Diabetes Metab Res Rev. 2015;31:336-43.

Esposito K, Chiodini P, Capuano A, Bellastella G, Maiorino MI, Parretta E, et al. Effect of metabolic syndrome and its components on prostate cancer risk: meta-analysis. J Endocrinol Invest. 2013;36:132-9.

Kasper JS, Liu Y, Giovannucci E. Diabetes mellitus and risk of prostate cancer in the health professionals follow-up study. Int J Cancer. 2009;124:1398-403.

Jayedi A, Djafarian K, Rezagholizadeh F, Mirzababaei A, Hajimohammadi M, Shab-Bidar S. Fasting blood glucose and risk of prostate cancer: A systematic review and meta-analysis of dose‒response. Diabetes Metab. 2018;44:320-7.

Abe S, Kawai K, Ishihara S, Nozawa H, Hata K, Kiyomatsu T, et al. Prognostic impact of carcinoembryonic antigen and carbohydrate antigen 19-9 in stage IV colorectal cancer patients after R0 resection. Journal of Surgical Research. 2016;205:384-92.

Ning S, Wei W, Li J, Hou B, Zhong J, Xie Y, et al. Clinical significance and diagnostic capacity of serum TK1, CEA, CA 19-9 and CA 72-4 levels in gastric and colorectal cancer patients. J Cancer. 2018;9:494-501.

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.

Limburg PJ, Vierkant RA, Fredericksen ZS, Leibson CL, Rizza RA, Gupta AK, et al. Clinically confirmed type 2 diabetes mellitus and colorectal cancer risk: a population-based, retrospective cohort study. Am J Gastroenterol. 2006;101:1872-9.