Evidence For Diabetes As A Risk Factor For Pancreatic Cancer

© 2003 Wang et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.

Everhart et al. examined 30 of the epidemiological studies that have looked at the association between diabetes and pancreatic cancer and used 20 of them in a meta-analysis [32]. The pooled relative risk from these studies was 2.1 for diabetes with a duration of at least l year prior to cancer diagnosis or death and 2.0 for diabetes with a duration of at least 5 years [32]. The authors concluded that pancreatic cancer could be added to the list of complications of diabetes [32]. Several epidemiological studies have analyzed relative risks associated with the different periods of time after the diagnosis of diabetes and have found a relatively modest but persistent increased risk of death from pancreatic cancer even when the diagnosis of diabetes preceded death by many years [32-37].

A population-based case-control study in the United States with 526 incident cases and 2,153 population controls showed a significant positive trend (P = 0.016) in risk with increasing years prior to diagnosis of cancer [36]. In other studies, the relative risk decreased with increasing follow-up time but remained significant [34,35,37]. However, other epidemiological studies have concluded that diabetes is not a risk factor for pancreatic cancer or else that it is not a risk factor if recently-diagnosed cases are excluded [6,38-40].

In patients with Type II diabetes (non-insulin-dependent diabetes), the pancreas is generally exposed to substantial hyperinsulinemia for years [33], suggesting that insulin may be involved in the association between long-standing diabetes and pancreatic cancer. A number of experiments have tested the hypothesis that insulin may stimulate the growth of pancreatic cancers. Binding studies have shown the presence of insulin receptors on pancreatic cancer cells [42-45]. In vitro studies have shown that insulin promotes growth of the hamster pancreatic cancer cell line H2T [42], the rat acinar pancreatic cancer cell line AR42J [45], and numerous human pancreatic cancer cells lines [44,46-51]. However, the human pancreatic cancer cell line SOJ-6 was not stimulated by insulin [46], and one of the studies using PANC-1 cells reported no response to exogenous insulin [49]. In addition to hyperinsulinemia, the increased blood glucose and free fatty acids in diabetes may also promote the growth of pancreatic cancer [52].

The genesis of the cancer is also influenced by the endocrine pancreas. In vivo studies concerning the effects of administration of exogenous insulin and/or induction of diabetes on pancreatic cancer have provided inconsistent data that reflect the complex interactions that may be involved in tumor growth [53-56]. Exogenous insulin significantly reduced the induction of benign and malignant pancreatic lesions in hamsters when given 2 hours before BOP <N-nitrosobis(2-oxopropyl)amine>, but the reduction in incidence was not significant when insulin was given simultaneously with BOP or 2 hours after BOP [53]. Cancer incidence in hamsters receiving insulin twice daily starting before BOP administration and continuing through the experimental period did not differ significantly from that in controls that received BOP only [54].

A study of pancreatic cancer in hamsters fed a high-fat diet that potentiated pancreatic cancer provided data suggesting that islet proliferation associated with insulin resistance enhances carcinogenesis [61]. In that study, high-fat-fed hamsters had elevated insulin levels but normal glucose levels, which was consistent with a state of insulin resistance [61].

Importance of Immune System in Diabetes

Pycnogenol (French maritime pine tree extract) Benefit for Diabetes

Diabetes & Pycnogenol Double Blinded Study

6.		AGullo L, Pezzilli R, Morselli-Labate AM: Diabetes and the risk of pancreatic cancer. Italian Pancreatic Cancer Study Group. N Engl J Med 1994, 331:81-84.
		Return to citation in text: [1]
32.		Everhart J, Wright D: Diabetes mellitus as a risk factor for pancreatic cancer. A meta-analysis. JAMA 1995, 273:1605-1609.
		Return to citation in text: [1] [2]
33.		Gapstur SM, Gann PH, Lowe W, Liu K K, Colangelo L, Dyer A: Abnormal glucose metabolism and pancreatic cancer mortality. JAMA 2000, 283:2552-2558.
		Return to citation in text: [1] [2]
34.		Calle EE, Murphy TK, Rodriguez C, Thun MJ, Heath CW Jr: Diabetes mellitus and pancreatic cancer mortality in a prospective cohort of United States adults. Cancer Causes Control 1998, 9:403-410.
		Return to citation in text: [1] [2]
35.		Wideroff L, Gridley G, Mellemkjaer L, Chow WH, Linet M, Keehn S, Borch-Johnsen K, Olsen JH: Cancer incidence in a population-based cohort of patients hospitalized with diabetes mellitus in Denmark. J Natl Cancer Inst 1997, 89:1360-1365.
		Return to citation in text: [1] [2]
36.		Silverman DT: Risk factors for pancreatic cancer: a case-control study based on direct interviews. Teratog Carcinog Mutagen 2001, 21:7-25.
		Return to citation in text: [1] [2]
37.		Chow WH, Gridley G, Nyren O, Linet MS, Ekbom A, Fraumeni JF Jr, Adami HO: Risk of pancreatic cancer following diabetes mellitus: a nationwide cohort study in Sweden. J Natl Cancer Inst 1995, 87:930-931.
		Return to citation in text: [1] [2]
38.		Gullo L: Diabetes and the risk of pancreatic cancer. Ann Oncol 1999, 10(Suppl 4):S79-S81.
		Return to citation in text: [1]
39.		Hjalgrim H, Frisch M, Ekbom A, Kyvik KO, Melbye M, Green A: Cancer and diabetes – a follow-up study of two population-based cohorts of diabetic patients. J Intern Med 1997, 241:471-475.
		Return to citation in text: [1]
40.		Frye JN, Inder WJ, Dobbs BR, Frizelle FA: Pancreatic cancer and diabetes: is there a relationship? A case-controlled study. Aust NZJ Surg 2000, 70:722-724.
		Return to citation in text: [1]
41.		Saltiel AR: New perspectives into the molecular pathogenesis and treatment of type 2 diabetes. Cell 2001, 104:517-529.
		Return to citation in text: [1]
42.		Fisher WE, Muscarella P, Boros LG, Schirmer WJ: Variable effect of streptozotocin-diabetes on the growth of hamster pancreatic cancer (H2T) in the Syrian hamster and nude mouse. Surgery 1998, 123:315-320.
		Return to citation in text: [1]
43.		Fisher WE, Boros LG, O'Dorisio TM, O'Dorisio MS, Schirmer WJ: GI hormonal changes in diabetes influence pancreatic cancer growth. J Surg Res 1995, 58:754-758.
		Return to citation in text: [1]
44.		Fisher WE, Boros LG, Schirmer WJ: Insulin promotes pancreatic cancer: evidence for endocrine influence on exocrine pancreatic tumors. J Surg Res 1996, 63:310-313.
		Return to citation in text: [1]
45.		Mossner J, Logsdon CD, Williams JA, Goldfine ID: Insulin, via its own receptor, regulates growth and amylase synthesis in pancreatic acinar AR42J cells. Diabetes 1985, 34:891-897.
		Return to citation in text: [1]
46.		Takeda Y, Escribano MJ: Effects of insulin and somatostatin on the growth and the colony formation of two human pancreatic cancer cell lines. J Cancer Res Clin Oncol 1991, 117:416-420.
		Return to citation in text: [1]
47.		Kornmann M, Maruyama H, Bergmann U, Tangvoranuntakul P, Beger HG, White MF, Korc M: Enhanced expression of the insulin receptor substrate-2 docking protein in human pancreatic cancer. Cancer Res 1998, 58:4250-4254.
		Return to citation in text: [1]
48.		Ding XZ, Fehsenfeld DM, Murphy LO, Permert J, Adrian TE: Physiological concentrations of insulin augment pancreatic cancer cell proliferation and glucose utilization by activating MAP kinase, PI3 kinase and enhancing GLUT-1 expression. Pancreas 2000, 21:310-320.
		Return to citation in text: [1]
49.		Beauchamp RD, Lyons RM, Yang EY, Coffey RJ Jr, Moses HL: Expression of and response to growth regulatory peptides by two human pancreatic carcinoma cell lines. Pancreas 1990, 5:369-380.
		Return to citation in text: [1]
50.		Wang F, Larsson J, Adrian TE, Gasslander T, Permert J: In vitro influences between pancreatic adenocarcinoma cells and pancreatic islets. J Surg Res 1998, 79:13-19.
		Return to citation in text: [1]
51.		Liehr RM, Melnykovych G, Solomon TE: Growth effects of regulatory peptides on human pancreatic cancer lines PANC-1 and MIA PaCa-2. Gastroenterology 1990, 98:1666-1674.
		Return to citation in text: [1]
52.		Fisher WE, Boros LG, Schirmer WJ: Reversal of enhanced pancreatic cancer growth in diabetes by insulin. Surgery 1995, 118:453-8.
		Return to citation in text: [1]
53.		Pour PM, Stepan K: Modification of pancreatic carcinogenesis in the hamster model. VIII. Inhibitory effect of exogenous insulin. J Natl Cancer Inst 1984, 72:1205-1208.
		Return to citation in text: [1]
54.		Pour PM, Kazakoff K, Carlson K: Inhibition of streptozotocin-induced islet cell tumors and N-nitrosobis(2-oxopropyl)amine-induced pancreatic exocrine tumors in Syrian hamsters by exogenous insulin. Cancer Res 1990, 50:1634-1639.
		Return to citation in text: [1]
55.		Bell RH Jr, McCullough PJ, Pour PM: Influence of diabetes on susceptibility to experimental pancreatic cancer. Am J Surg 1988, 155:159-164.
		Return to citation in text: [1]
56.		Povoski SP, Fenoglio-Preiser CM, Sayers HJ, McCullough PJ, Zhou W, Bell RH Jr: Effect of streptozotocin diabetes on development of nitrosamine-induced pancreatic carcinoma when diabetes induction occurs after nitrosamine exposure. Carcinogenesis 1993, 14:961-967.
		Return to citation in text: [1]
57.		Pour PM, Duckworth W, Carlson K, Kazakoff K: Insulin therapy prevents spontaneous recovery from streptozotocin-induced diabetes in Syrian hamsters. An autoradiographic and immunohistochemical study. Virchows Arch A Pathol Anat Histopathol 1990, 417:333-341.
		Return to citation in text: [1]
58.		Ishikawa O, Ohigashi H, Imaoka S, Nakai I, Mitsuo M, Weide L, Pour PM: The role of pancreatic islets in experimental pancreatic carcinogenicity. Am J Pathol 1995, 147:1456-1464.
		Return to citation in text: [1]
59.		Pour PM, Weide L, Liu G, Kazakoff K, Scheetz M, Toshkov I, Ikematsu Y, Fienhold MA, Sanger W: Experimental evidence for the origin of ductal-type adenocarcinoma from the islets of Langerhans. Am J Pathol 1997, 150:2167-2180.
		Return to citation in text: [1]
60.		Fienhold MA, Kazakoff K, Pour PM: The effect of streptozotocin and a high-fat diet on BOP-induced tumors in the pancreas and in the submandibular gland of hamsters bearing transplants of homologous islets. Cancer Lett 1997, 117:155-160.
		Return to citation in text: [1]
61.		Schneider MB, Matsuzaki H, Haorah J, Ulrich A, Standop J, Ding XZ, Adrian TE, Pour PM: Prevention of pancreatic cancer induction in hamsters by metformin. Gastroenterology 2001, 120:1263-1270.
		Return to citation in text: [1]

Transfer Factor can strengthen your immune cells (NK cells) by educating them to recognise harmful invasion to your body, remember the past invasion and respond accordingly with the best possible way.  Natural Killer cells are known for the important roll in the fight against cancer.  Find out more about Cancer and Natural Killer Cells