Diabetes Metab J.  2011 Jun;35(3):193-198. 10.4093/dmj.2011.35.3.193.

Diabetes and Cancer: Is Diabetes Causally Related to Cancer?

Affiliations
  • 1Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. kw1234@skku.edu

Abstract

Diabetes mellitus is a serious and growing health problem worldwide and is associated with severe acute and chronic complications. Moreover, epidemiologic evidence suggests that people with diabetes are at significantly higher risk for many forms of cancer. Several studies indicate an association between diabetes and the risk of liver, pancreas, endometrium, colon/rectum, breast, and bladder cancer. Mortality is also moderately increased in subjects with diabetes. Common risk factors such as age, obesity, physical inactivity and smoking may contribute to increased cancer risk in diabetic patients. Hyperinsulinemia most likely favors cancer in diabetic patients as insulin is a growth factor with pre-eminent metabolic as well as mitogenic effects, and its action in malignant cells is favored by mechanisms acting at both the receptor and post-receptor level. The effect of diabetes treatment drugs, aside from metformin, on cancer is not conclusive. In order to fight the perfect storm of diabetes and cancer, strategies to promote primary prevention and early detection of these conditions are urgently needed.

Keyword

Diabetes mellitus; Cancer; Mortality

MeSH Terms

Breast
Diabetes Mellitus
Endometrium
Female
Humans
Hyperinsulinism
Insulin
Liver
Metformin
Obesity
Pancreas
Primary Prevention
Risk Factors
Smoke
Smoking
Urinary Bladder Neoplasms
Insulin
Metformin
Smoke

Cited by  1 articles

Diabetes and Cancer: Cancer Should Be Screened in Routine Diabetes Assessment
Sunghwan Suh, Kwang-Won Kim
Diabetes Metab J. 2019;43(6):733-743.    doi: 10.4093/dmj.2019.0177.


Reference

1. Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care. 2004. 27:1047–1053.
2. Lopez AD, Mathers CD, Ezzati M, Jamison DT, Murray CJ. Global and regional burden of disease and risk factors, 2001: systematic analysis of population health data. Lancet. 2006. 367:1747–1757.
3. Statistics Korea: Statistics of Cause of Death. Available from: http://www.kostat.go.kr. (updated 2010 Sep 9).
4. Vigneri P, Frasca F, Sciacca L, Pandini G, Vigneri R. Diabetes and cancer. Endocr Relat Cancer. 2009. 16:1103–1123.
5. Nicolucci A. Epidemiological aspects of neoplasms in diabetes. Acta Diabetol. 2010. 47:87–95.
6. Tsugane S, Inoue M. Insulin resistance and cancer: epidemiological evidence. Cancer Sci. 2010. 101:1073–1079.
7. Giovannucci E, Harlan DM, Archer MC, Bergenstal RM, Gapstur SM, Habel LA, Pollak M, Regensteiner JG, Yee D. Diabetes and cancer: a consensus report. Diabetes Care. 2010. 33:1674–1685.
8. Park SK, Park MK, Suk JH, Kim MK, Kim YK, Kim IJ, Kang YH, Lee KJ, Lee HS, Lee CW, Kim BH, Lee KI, Kim MK, Kim DK. Cause-of-death trends for diabetes mellitus over 10 years. Korean Diabetes J. 2009. 33:65–72.
9. Nicolucci A. Epidemiological aspects of neoplasms in diabetes. Acta Diabetol. 2010. 47:87–95.
10. Jee SH, Ohrr H, Sull JW, Yun JE, Ji M, Samet JM. Fasting serum glucose level and cancer risk in Korean men and women. JAMA. 2005. 293:194–202.
11. Park YJ, Kim KW, Oh EY, Min YK, Lee MS, Lee MK, Lee JK, Lee KT, Kim YI, Choi YH. Prevalence of diabetes mellitus in pancreatic cancer patients. J Korean Diabetes Assoc. 2001. 25:316–322.
12. Inoue M, Iwasaki M, Otani T, Sasazuki S, Noda M, Tsugane S. Diabetes mellitus and the risk of cancer: results from a large-scale population-based cohort study in Japan. Arch Intern Med. 2006. 166:1871–1877.
13. Zendehdel K, Nyren O, Ostenson CG, Adami HO, Ekbom A, Ye W. Cancer incidence in patients with type 1 diabetes mellitus: a population-based cohort study in Sweden. J Natl Cancer Inst. 2003. 95:1797–1800.
14. Swerdlow AJ, Laing SP, Qiao Z, Slater SD, Burden AC, Botha JL, Waugh NR, Morris AD, Gatling W, Gale EA, Patterson CC, Keen H. Cancer incidence and mortality in patients with insulin-treated diabetes: a UK cohort study. Br J Cancer. 2005. 92:2070–2075.
15. Barone BB, Yeh HC, Snyder CF, Peairs KS, Stein KB, Derr RL, Wolff AC, Brancati FL. Long-term all-cause mortality in cancer patients with preexisting diabetes mellitus: a systematic review and meta-analysis. JAMA. 2008. 300:2754–2764.
16. Ko C, Chaudhry S. The need for a multidisciplinary approach to cancer care. J Surg Res. 2002. 105:53–57.
17. Centers for Disease Control and Prevention (CDC). Cancer survivorship--United States, 1971-2001. MMWR Morb Mortal Wkly Rep. 2004. 53:526–529.
18. Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med. 2003. 348:1625–1638.
19. Adami HO, Trichopoulos D. Obesity and mortality from cancer. N Engl J Med. 2003. 348:1623–1624.
20. Vigneri P, Frasca F, Sciacca L, Frittitta L, Vigneri R. Obesity and cancer. Nutr Metab Cardiovasc Dis. 2006. 16:1–7.
21. Friedenreich CM, Orenstein MR. Physical activity and cancer prevention: etiologic evidence and biological mechanisms. J Nutr. 2002. 132:11 Suppl. 3456S–3464S.
22. Lee IM. Physical activity and cancer prevention: data from epidemiologic studies. Med Sci Sports Exerc. 2003. 35:1823–1827.
23. Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, Nathan DM. Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002. 346:393–403.
24. Pan XR, Li GW, Hu YH, Wang JX, Yang WY, An ZX, Hu ZX, Lin J, Xiao JZ, Cao HB, Liu PA, Jiang XG, Jiang YY, Wang JP, Zheng H, Zhang H, Bennett PH, Howard BV. Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance. The Da Qing IGT and Diabetes Study. Diabetes Care. 1997. 20:537–544.
25. Tuomilehto J, Lindstrom J, Eriksson JG, Valle TT, Hamalainen H, Ilanne-Parikka P, Keinanen-Kiukaanniemi S, Laakso M, Louheranta A, Rastas M, Salminen V, Uusitupa M. Finnish Diabetes Prevention Study Group. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med. 2001. 344:1343–1350.
26. Kosaka K, Noda M, Kuzuya T. Prevention of type 2 diabetes by lifestyle intervention: a Japanese trial in IGT males. Diabetes Res Clin Pract. 2005. 67:152–162.
27. Mackay J, Ericksen M, Shafey O. The cancer atlas. 2006. Atlanta: American Cancer Society.
28. Foy CG, Bell RA, Farmer DF, Goff DC Jr, Wagenknecht LE. Smoking and incidence of diabetes among U.S. adults: findings from the Insulin Resistance Atherosclerosis Study. Diabetes Care. 2005. 28:2501–2507.
29. Willi C, Bodenmann P, Ghali WA, Faris PD, Cornuz J. Active smoking and the risk of type 2 diabetes: a systematic review and meta-analysis. JAMA. 2007. 298:2654–2664.
30. Heuson JC, Legros N. Influence of insulin deprivation on growth of the 7,12-dimethylbenz(a)anthracene-induced mammary carcinoma in rats subjected to alloxan diabetes and food restriction. Cancer Res. 1972. 32:226–232.
31. 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. 32:233–238.
32. Calle EE, Kaaks R. Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nat Rev Cancer. 2004. 4:579–591.
33. Papa V, Pezzino V, Costantino A, Belfiore A, Giuffrida D, Frittitta L, Vannelli GB, Brand R, Goldfine ID, Vigneri R. Elevated insulin receptor content in human breast cancer. J Clin Invest. 1990. 86:1503–1510.
34. Frasca F, Pandini G, Scalia P, Sciacca L, Mineo R, Costantino A, Goldfine ID, Belfiore A, Vigneri R. Insulin receptor isoform A, a newly recognized, high-affinity insulin-like growth factor II receptor in fetal and cancer cells. Mol Cell Biol. 1999. 19:3278–3288.
35. De Meyts P, Christoffersen CT, Urso B, Wallach B, Gronskov K, Yakushiji F, Shymko RM. Role of the time factor in signaling specificity: application to mitogenic and metabolic signaling by the insulin and insulin-like growth factor-I receptor tyrosine kinases. Metabolism. 1995. 44:10 Suppl 4. 2–11.
36. Currie CJ, Poole CD, Gale EA. The influence of glucose-lowering therapies on cancer risk in type 2 diabetes. Diabetologia. 2009. 52:1766–1777.
37. Jonasson JM, Ljung R, Talback M, Haglund B, Gudbjornsdottir S, Steineck G. Insulin glargine use and short-term incidence of malignancies-a population-based follow-up study in Sweden. Diabetologia. 2009. 52:1745–1754.
38. Colhoun HM. SDRN Epidemiology Group. Use of insulin glargine and cancer incidence in Scotland: a study from the Scottish Diabetes Research Network Epidemiology Group. Diabetologia. 2009. 52:1755–1765.
39. Hemkens LG, Grouven U, Bender R, Gunster C, Gutschmidt S, Selke GW, Sawicki PT. Risk of malignancies in patients with diabetes treated with human insulin or insulin analogues: a cohort study. Diabetologia. 2009. 52:1732–1744.
40. Rosenstock J, Fonseca V, McGill JB, Riddle M, Halle JP, Hramiak I, Johnston P, Davis M. Similar risk of malignancy with insulin glargine and neutral protamine Hagedorn (NPH) insulin in patients with type 2 diabetes: findings from a 5 year randomised, open-label study. Diabetologia. 2009. 52:1971–1973.
41. Pollak M, Russell-Jones D. Insulin analogues and cancer risk: cause for concern or cause célèbre? Int J Clin Pract. 2010. 64:628–636.
42. Gerstein HC. Does insulin therapy promote, reduce, or have a neutral effect on cancers? JAMA. 2010. 303:446–447.
43. Smith U, Gale EA. Does diabetes therapy influence the risk of cancer? Diabetologia. 2009. 52:1699–1708.
44. Monami M, Lamanna C, Balzi D, Marchionni N, Mannucci E. Sulphonylureas and cancer: a case-control study. Acta Diabetol. 2009. 46:279–284.
45. Evans JM, Donnelly LA, Emslie-Smith AM, Alessi DR, Morris AD. Metformin and reduced risk of cancer in diabetic patients. BMJ. 2005. 330:1304–1305.
46. Bowker SL, Majumdar SR, Veugelers P, Johnson JA. Increased cancer-related mortality for patients with type 2 diabetes who use sulfonylureas or insulin. Diabetes Care. 2006. 29:254–258.
47. Wright JL, Stanford JL. Metformin use and prostate cancer in Caucasian men: results from a population-based case-control study. Cancer Causes Control. 2009. 20:1617–1622.
48. Landman GW, Kleefstra N, van Hateren KJ, Groenier KH, Gans RO, Bilo HJ. Metformin associated with lower cancer mortality in type 2 diabetes: ZODIAC-16. Diabetes Care. 2010. 33:322–326.
49. Cazzaniga M, Bonanni B, Guerrieri-Gonzaga A, Decensi A. Is it time to test metformin in breast cancer clinical trials? Cancer Epidemiol Biomarkers Prev. 2009. 18:701–705.
50. Goodwin PJ, Ligibel JA, Stambolic V. Metformin in breast cancer: time for action. J Clin Oncol. 2009. 27:3271–3273.
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