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BMC Cancer
Published in: BMC Cancer 1/2016

Open Access 01-12-2016 | Research article

Risk factors for cancer development in type 2 diabetes: A retrospective case-control study

Authors: Mariusz Dąbrowski, Elektra Szymańska-Garbacz, Zofia Miszczyszyn, Tadeusz Dereziński, Leszek Czupryniak

Published in: BMC Cancer | Issue 1/2016

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Abstract

Background

The risk of several types of cancer is increased in type 2 diabetes mellitus. The earliest possible diagnosis of cancer – difficult within regular outpatient diabetes care - is of utmost importance for patients’ survival. The aim of this multicenter, retrospective (years 1998–2015), case-control study was to identify risk factors associated with malignancy in subjects with diabetes treated in a typical outpatient setting.

Methods

In the databases of 3 diabetic and 1 primary care clinics 203 patients (115 women) with type 2 diabetes mellitus who developed malignancy while treated for diabetes were identified. The control group consisted of 203 strictly age- and gender matched subjects with type 2 diabetes without cancer. Factors associated with diabetes: disease duration, antidiabetic medications use and metabolic control of diabetes were analyzed. Also other variables: BMI (body mass index), smoking habits, place of residence and comorbidities were included into analysis.

Results

The most prevalent malignancies in men and women together were breast cancer (20.7 %) and colorectal cancer (16.3 %). HbA1c (hemoglobin A1c) level ≥8.5 %, obesity and insulin treatment in dose-dependent and time-varying manner demonstrated significant association with increased risk of malignancy, while metformin use was associated with a lower risk of cancer. Diabetes duration, comorbidities, smoking habits, place of residence and aspirin use did not show significant association with risk of malignancy.

Conclusions

In the outpatient setting the obese patients with poorly controlled insulin treated type 2 diabetes mellitus should be rigorously assessed towards malignancies, particularly breast cancer in women and colorectal cancer in men.
Literature
1.
Greenwood M, Wood F. The relation between the cancer and diabetes death rates. J Hyg (Lond). 1914;14:83–118.CrossRef
2.
Rohdenburg GL, Bernhard A, Krehbiel O. Sugar tolerance in cancer. J Am Med Assoc. 1919;72:1528–30.CrossRef
3.
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;28:109–22.CrossRefPubMed
4.
Ben Q, Xu M, Ning X, et al. Diabetes mellitus and risk of pancreatic cancer: a meta-analysis of cohort studies. Eur J Cancer. 2011;47:1928–37.CrossRefPubMed
5.
Sun L, Yu S. Diabetes mellitus is an independent risk factor for colorectal cancer. Dig Dis Sci. 2012;57:1586–97.CrossRefPubMed
6.
Tian T, Zhang LQ, Ma XH, Zhou JN, Shen J. Diabetes mellitus and incidence and mortality of gastric cancer: a meta-analysis. Exp Clin Endocrinol Diabetes. 2012;120:217–23.CrossRefPubMed
7.
Bao C, Yang X, Xu W, et al. Diabetes mellitus and incidence and mortality of kidney cancer: a meta-analysis. J Diabetes Compl. 2013;27:357–64.CrossRef
8.
Yang X-Q, Xu C, Sun Y, Han R-F. Diabetes mellitus increases the risk of bladder cancer: an updated meta-analysis. Asian Pacific J Cancer Prev. 2013;14:2583–9.CrossRef
9.
Zhang ZH, Su PY, Hao JH, Sun YH. The role of preexisting diabetes mellitus on incidence and mortality of endometrial cancer: a meta-analysis of prospective cohort studies. Int J Gynecol Cancer. 2013;23:294–303.CrossRefPubMed
10.
11.
Castillo JJ, Mull N, Reagan JL, Nemr S, Mitri J. Increased incidence of non-Hodgkin lymphoma, leukemia, and myeloma in patients with diabetes mellitus type 2: a meta-analysis of observational studies. Blood. 2012;119:4845–50.CrossRefPubMedPubMedCentral
12.
Turati F, Negri E, La Vecchia C. Family history and the risk of cancer: genetic factors influencing multiple cancer sites. Expert Rev Anticancer Ther. 2014;14:1–4.CrossRefPubMed
13.
Espina C, Straif K, Friis S, et al. European code against cancer 4th edition: environment, occupation and cancer. Cancer Epidemiol. 2015;39 Suppl 1:S84–92.CrossRefPubMed
14.
Dąbrowski M. Cukrzyca a nowotwory (Diabetes and cancer). Diabet Prakt. 2010;11:54–63 (in Polish).
15.
Giovanucci E, Harlan DM, Archer MC, et al. Diabetes and cancer: a consensus report. Diabetes Care. 2010;33:1674–85.CrossRef
16.
Handelsman Y, LeRoith D, Bloomgarden ZT, et al. Diabetes and cancer – an AACE/ACE consensus statement. Diabetes Cancer Endocr Pract. 2013;19:675–93.PubMed
17.
18.
Janghorbani M, Dehghani M, Salehi-Marzijarani M. Systematic review and meta-analysis of insulin therapy and risk of cancer. Horm Cancer. 2012;3:137–46.CrossRefPubMed
19.
Lutz SZ, Staiger H, Fritsche A, Häring HU. Antihyperglycaemic therapies and cancer risk. Diab Vasc Dis Res. 2014;11:371–89.CrossRefPubMed
20.
21.
22.
Bansal D, Bhansali A, Kapil G, Undela K, Tiwari P. Type 2 diabetes and risk of prostate cancer: a meta-analysis of observational studies. Prostate Cancer Prostatic Dis. 2013;16:151–8.PubMed
23.
Yang X, Ko GTC, So WY, 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.CrossRefPubMedPubMedCentral
24.
Donadon V, Balbi M, Valent F, Avogaro A. Glycated hemoglobin and antidiabetic strategies as risk factors for hepatocellular carcinoma. World J Gastroenterol. 2010;16(24):3025–32.CrossRefPubMedPubMedCentral
25.
Dąbrowski M. Glycated hemoglobin, diabetes treatment and cancer risk in type 2 diabetes. A case–control study. Ann Agricult Environment Med. 2013;20:116–21.
26.
Travier N, Jeffreys M, Brewer N, et al. Association between glycosylated hemoglobin and cancer risk: a New Zealand linkage study. Ann Oncol. 2007;18:1414–9.CrossRefPubMed
27.
Joshu CE, Prizment AE, Dluzniewski PJ, et al. Glycated hemoglobin and cancer incidence and mortality in the Atherosclerosis in Communities (ARIC) study, 1990–2006. Int J Cancer. 2012;131:1667–77.CrossRefPubMedPubMedCentral
28.
Siddiqui AA, Spechler SJ, Huerta S, Dredar S, Little BB, Cryer B. Elevated HbA1c is an independent predictor of aggressive clinical behavior in patients with colorectal cancer: a case–control study. Dig Dis Sci. 2008;53:2486–94.CrossRefPubMed
29.
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(6), e38784.CrossRefPubMedPubMedCentral
30.
de Beer JC, Liebenberg L. Does cancer risk increase with HbA1c, independent of diabetes? British J Cancer. 2014;110:2361–8.CrossRef
31.
32.
33.
34.
Heuson JC, Legros N, Heimann R. Influence of insulin administration on growth of the 7,12-dimethylbenz(a)anthracene-induced mammary carcinoma in intact, oophorectomized, and hypophysectomized rats. Cancer Res. 1972;32:233–8.PubMed
35.
Johnson JA, Bowker SL, Richardson K, Marra CA. Time-varying incidence of cancer after the onset of type 2 diabetes: evidence of potential detection bias. Diabetologia. 2011;54:2263–71.CrossRefPubMed
36.
Carstensen B, Witte DR, Friis S. Cancer occurrence in Danish diabetic patients: duration and insulin effects. Diabetologia. 2012;55:948–58.CrossRefPubMed
37.
Li C, Zhao G, Okoro CA, Wen XJ, Ford ES, Balluz LS. Prevalence of diagnosed cancer according to duration of diagnosed diabetes and current insulin use among U.S. adults with diagnosed diabetes: findings from the 2009 Behavioral Risk Factor Surveillance System. Diabetes Care. 2013;36:1569–76.CrossRefPubMedPubMedCentral
38.
Dąbrowski M, Grondecka A. Diabetes is a risk factor of hospitalization in the surgical ward due to the cancer in elderly and middle-aged population. Arch Med Sci 2016, DOI: 10.​5114/​aoms.​2016.​58666, Published online 22 Mar 2016
39.
Soranna D, Scotti L, Zambon A, et al. Cancer risk associated with use of metformin and sulfonylurea in type 2 diabetes: a meta-analysis. Oncologist. 2012;17:813–22.CrossRefPubMedPubMedCentral
40.
Thakkar B, Aronis KN, Vamvini MT, Shields K, Mantzoros CS. Metformin and sulfonylureas in relation to cancer risk in type II diabetes patients: a meta-analysis using primary data of published studies. Metabolism. 2013;62:922–34.CrossRefPubMed
41.
Kowall B, Stang A, Rathmann W, Kostev K. No reduced risk of overall, colorectal, lung, breast, and prostate cancer with metformin therapy in diabetic patients: database analyses from Germany and the UK. Pharmacoepidemiol Drug Saf. 2015;24:865–74.CrossRefPubMed
42.
Aljada A, Mousa SA. Metformin and neoplasia: implications and indications. Pharmacol Ther. 2012;133:108–15.CrossRefPubMed
43.
Eikawa S, Nishida M, Mizukami S, Yamazaki C, Nakayama E, Udono H. Immune-mediated antitumor effect by type 2 diabetes drug, metformin. Proc Natl Acad Sci U S A. 2015;112:1809–14.CrossRefPubMedPubMedCentral
44.
Monami M, Lamanna C, Balzi D, Marchionni N, Mannucci E. Sulphonylureas and cancer: a case-control study. Acta Diabetol. 2009;46:279–84.CrossRefPubMed
45.
Holden SE, Jenkins-Jones S, Morgan CL, Schernthaner G, Currie CJ. Glucose-lowering with exogenous insulin monotherapy in type 2 diabetes: dose association with all-cause mortality, cardiovascular events and cancer. Diabetes Obes Metab. 2015;17:350–62.CrossRefPubMed
46.
Forssas E, Sund R, Manderbacka K, Arffman M, Ilanne-Parikka P, Keskimäki I. Increased cancer mortality in diabetic people treated with insulin: a register-based follow-up study. BMC Health Serv Res. 2013;13:267.CrossRefPubMedPubMedCentral
47.
48.
Vigneri P, Frasca F, Sciacca L, Pandini G, Vigneri R. Diabetes and cancer. Endocr Relat Cancer. 2009;16:1103–23.CrossRefPubMed
49.
Gerstein HC. Does insulin therapy promote, reduce, or have a neutral effect on cancers? JAMA. 2010;303:446–7.CrossRefPubMed
50.
The ORIGIN Trial Investigators, Gerstein HC, Bosch J, Dagenais GR, et al. Basal insulin and cardiovascular and other outcomes in dysglycemia. N Engl J Med. 2012;367:319–28.CrossRef
51.
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;371:569–78.CrossRefPubMed
52.
53.
Garg SK, Maurer H, Reed K, Selagamsetty R. Diabetes and cancer: two diseases with obesity as a common risk factor. Diabetes Obes Metab. 2014;16:97–110.CrossRefPubMed
54.
Gandini S, Botteri E, Iodice S, et al. Tobacco smoking and cancer: a meta-analysis. Int J Cancer. 2008;122:155–64.CrossRefPubMed
55.
Metadata
Title
Risk factors for cancer development in type 2 diabetes: A retrospective case-control study
Authors
Mariusz Dąbrowski
Elektra Szymańska-Garbacz
Zofia Miszczyszyn
Tadeusz Dereziński
Leszek Czupryniak
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2016
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-016-2836-6

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