Aim In order to increase the database related to the antineoplastic potential of metformin, association between the use of metformin and risk of cancer occurence in patients with diabetes mellitus type 2 (DM2) was investigated. Methods In this cross-sectional study, medical records of patients with DM2 were reviewed for cancer occurence. Data on age, body mass index (BMI), alcohol and nicotine consumption, glucose and HbA1c levels, duration of DM2, medication used in the treatment of DM2 and cancer occurence were collected and analyzed. Unpaired Student's t-test or Mann-Whitney U test were used for comparisons between treatment groups, and logistic regression to asses how well our set of predictor variables predicts occurence of carcinoma. P-value less than 0.05 was considered statistically significant. Results The mean age of 234 included patients was 66.8±11.5 years, and DM2 duration was 7± 6.49 years. Mean glucose value was 8.51±4.17mmol/L, and HbA1c 7.74±1.53. Metformin therapy was prescribed in 190 (81%) patients. Cancer was diagnosed in 16 (6.8%) patients: prostate cancer in eight (3.4%), breast cancer in four (1.7%), rectal cancer in two (0.9%) and cancer of the uterus and cervix in one patient. Age, duration of DM2 and BMI did not contribute significantly to the model, while metformin use was shown to be a significant independent predictor (OR=0.049; 95% CI=0.013-0.181; p=0.001). Conclusion Our findings support the hypothesis that the use of metformin compared to the use of other oral antidiabetic drugs is associated with a lower risk of cancer in patients with DM2.
Huxley R, Ansary-Moghaddam A, De González A, Barzi F, Woodward M. Type-II diabetes and pancreatic cancer: a meta-analysis of 36 studies. Br J Cancer 2005:2076–83.
2
Cancer Research UK. Cancer incidence by age n.d.
3
Calle E, Rodriguez C, Walker-Thurmond K, Thun M. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med 2003:1625–38.
4
Togashi Y, Hayashi H, Okamoto K, Fumita S, Terashima M, De Velasco M, et al. Chronic nicotine exposure mediates resistance to EGFR-TKI in EGFR-mutated lung cancer via an EGFR signal. Lung Cancer 2015:16–23.
5
Cancer facts and figures 2017.
6
Larsson S, Mantzoros C, Wolk A. Diabetes mellitus and risk of breast cancer: a meta-analysis. Int J Cancer 2007:856–62.
7
Friberg E, Orsini N, Mantzoros C, Wolk A. Diabetes mellitus and risk of endometrial cancer: a metaanalysis. Diabetologia 2007:1365–74.
8
Wang P, Kang D, Cao W, Wang Y, Liu Z. Diabetes mellitus and risk of hepatocellular carcinoma: a systematic review and meta-analysis. Diabetes Metab Res Rev 2012:109–22.
9
El-Serag H, Hampel H, Javadi F. The association between diabetes and hepatocellular carcinoma: a systematic review of epidemiologic evidence. Clin Gastroenterol Hepatol 2006:369–80.
10
Li K-L, Li L, Zhang P, Kang J, Wang Y-B, Chen H-Y, et al. A multicenter double-blind phase II study of metformin with gefitinib as first-line therapy of locally advanced non-small-cell lung cancer. Clin Lung Cancer 2017:340–3.
11
Zhu Z, Wang X, Shen Z, Lu Y, Zhong S, Xu C. Risk of bladder cancer in patients with diabetes mellitus: an updated meta-analysis of 36 observational studies. BMC Cancer 2013:310.
12
Mitri J, Castillo J, Pittas A. Diabetes and risk of non-Hodgkin’s lymphoma: A meta-analysis of observational studies. Diabetes Care 2008:2391–7.
13
Deng L, Gui Z, Zhao L, Wang J, Shen L. Diabetes mellitus and the incidence of colorectal cancer: an updated systematic review and meta-analysis. Dig Dis Sci 2012:1576–85.
14
Barone B, Yeh H, Snyder C, Peairs K, Stein K, Derr R, et al. Long-term all-cause mortality in cancer patients with preexisting diabetes mellitus: a systematic review and meta-analysis. JAMA 2008:2754–64.
15
Garg S, Maurer H, Reed K, Selagamsetty R. Diabetes and cancer: two diseases with obesity as a common risk factor. Diabetes Obes Metab 2014:97–110.
16
Onitilo A, Stankowski R, Berg R, Engel J, Glurich I, Williams G, et al. Type 2 diabetes mellitus, glycemic control, and cancer risk. Eur J Cancer Prev 2014:134–40.
17
Margel D, Urbach D, Lipscombe L, Bell C, Kulkarni G, Austin P, et al. Association between metformin use and risk of prostate cancer and its grade. J Natl Cancer Inst 2013:1123–31.
18
Mičić D, Cvijović G, Trajković V, Duntas L, Metformin P. its emerging role in oncology. Hormones 2011:5–15.
19
Libby G, Donnelly L, Donnan P. New users of metformin area at low risk of incident cancer: a cohort study among people with type 2 diabetes. Diabetes Care 2009:1620–5.
20
Godarzi M, Ash B, M. Metformin revisited: reevaluation of its properties and role in the pharmacopoeia of modern antidiabetic agents. Diabetes Obes Metab 2005:654–65.
21
Gosmanova E, Canada R, Mangold T, Rawls W, Wall B. Effect of metformin-containing antidiabetic regimens on all-cause mortality in veterans with type 2 diabetes mellitus. Am J Med Sci 2008:241–7.
22
Evans J, Ogston S, Emslie-Smith A, Morris A. Risk of mortality and adverse cardiovascular outcomes in type 2 diabetes: a comparison of patients treated with sulfonylureas and metformin. Diabetologia 2006:930–6.
23
Evans J, Donnelly L, Smith E-, Alessi A, Morris D, A. Metformin and reduced risk of cancer in diabetic patients. BMJ 2005:1304–5.
24
Bowker S, Majumdar S, Veugelers P, Johnson J. Increased cancer-related mortality for patients with type 2 diabetes who use sulfonylureas or insulin. Diabetes Care 2006:254–8.
25
Lemke T, Williams D, Roche V, Zito S. Foye’s principles of medicinal chemistry. 6 th ed. Philadelphia 2008.
26
Viollet B, Guigas B, Garcia S, Leclerc N, Foretz J, Andreelli M, et al. Cellular and molecular mechanisms of metformin: an overview. Clin Sci 2012:253–70.
27
Gandini S, Puntoni M, Heckman-Stoddard B, Dunn B, Ford L, Censi D, et al. Metformin and cancer risk and mortality: a systematic review and meta-analysis taking into account biases and confounders. Cancer Prev Res (Phila) 2014:867–85.
28
Sun G, Kashyap S. Cancer risk in type 2 diabetes mellitus: metabolic Llnks and therapeutic considerations. J Nutr Metab 2011:708183.
29
Li W, Saud S, Young M, Chen G, Hua B. Targeting AMPK for cancer prevention and treatment. Oncotarget 2015:7365–78.
30
Luo Z, Zang M, Guo W. AMPK as a metabolic tumor suppressor: control of metabolism and cell growth. Future Oncol 2010:457–70.
31
Thompson M, Grubbs C, Bode A, Reid J, Mcgovern R, Bernard P, et al. Lack of effect of metformin on mammary carcinogenesis in nondiabetic rat and mouse models. Cancer Prev Res 2015:231–9.
32
Anisimov V, Berstein L, Popovich I, Zabezhinski M, Egormin P, Piskunova T, et al. Poroshina TE. If started early in life, metformin treatment increases life span and postpones tumors in female SHR mice. Aging (Albany NY) 2011:148–57.
33
Noto H, Goto A, Tsujimoto T, Noda M. Cancer risk in diabetic patients treated with metformin: a systematic review and meta-analysis. PLoS One 2012:33411.
34
Franciosi M, Lucisano G, Lapice E, Strippoli G, Pellegrini F, Nicolucci A. Metformin therapy and risk of cancer in patients with type 2 diabetes: systematic review. PLoS One 2013:71583.
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