Influence of diabetes on susceptibility to experimental pancreatic cancer

Bell, Richard H.; McCullough, Patrick J.; Pour, Parviz M.

doi:10.1016/s0002-9610(88)80274-5

Cited by 39 publications

(12 citation statements)

References 11 publications

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“…The intra-insular ductules proliferate forming either benign patterns consistent with human pancreatic microcystic adenomas or becoming increasingly hyperplastic, dysplastic and atypical and culminating in the formation of malignant glands that destroy the islets and invade the surrounding tissues, even when they are of microscopic size (4)(5)(6)8). The following observations support the role of islets in pancreatic ductal carcinomas: (i) streptozotocin pretreatment, which causes destruction of β-cells, inhibits the pancreatic carcinogenicity of N-nitrosobis(2-oxopropyl)amine (BOP) at low doses or prevents it at high doses (12)(13)(14); (ii) genetically diabetic hamsters with atrophic islets are resistant to the pancreatic carcinogenic effects of BOP, whereas the pancreas of a non-diabetic strain with intact islets is susceptible (15); (iii) induction of nesidioblastosis enhances pancreatic carcinogenesis (16); and (iv) transplantation of homologous islets into the submandibular gland (SMG) of recipient hamsters and subsequent BOP treatment induces invasive and metastasizing ductal-type adenocarcinomas, histological and immunohistochemical analyses of which point to the derivation of tumors from within islets (9)(10)(11).…”

Section: Introductionmentioning

confidence: 67%

Induction of adenocarcinoma from hamster pancreatic islet cells treated with N-nitrosobis(2-oxopropyl)amine in vitro

et al. 1999

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Section: Introductionmentioning

confidence: 67%

Induction of adenocarcinoma from hamster pancreatic islet cells treated with N-nitrosobis(2-oxopropyl)amine in vitro

et al. 1999

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“…Biomarkers of insulin resistance have been associated with increased pancreatic cancer risk in prospective epidemiologic studies (2,3,(22)(23)(24)(25). Experimental studies have shown that insulin has mitogenic effects on pancreatic cancer cell lines (26) and peripheral insulin resistance promotes ductal pancreatic carcinogenesis in animals (27)(28)(29)(30)(31). Experimental and epidemiologic studies also suggest that administration of certain antidiabetic drugs such as metformin, an insulin sensitizer, decreases pancreatic cancer risk and progression, whereas insulin and insulin secretagogues increase risk (5,21,30,32,33).…”

Section: Discussionmentioning

confidence: 99%

Lifetime adiposity and risk of pancreatic cancer in the NIH-AARP Diet and Health Study cohort

Stolzenberg‐Solomon¹,

Schairer²,

Moore³

et al. 2013

The American Journal of Clinical Nutrition

101

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Background: The association of excess body weight across a lifetime with pancreatic cancer has not been examined extensively. Objective: We determined the association for body mass index (BMI) at different ages and adiposity duration and gain with incident pancreatic adenocarcinoma in the NIH-AARP Diet and Health Study cohort. Design: Participants aged 50-71 y completed questionnaires at baseline (1995)(1996) and 6 months later that queried height and weight history. We calculated HRs and 95% CIs by using Cox proportional hazards models adjusted for age, smoking, sex, and intakes of energy and total fat. Results: Over an average follow-up of 10.5 y, 1206 and 2122 pancreatic cancer cases were identified in the subcohort who completed the second questionnaire (n = 273,975) and the baseline cohort (n = 501,698), respectively. Compared with normal weight, overweight or obesity at ages 18, 35, 50, or .50 y (baseline BMI) was significantly associated with pancreatic cancer, with HRs ranging from 1.15 to 1.53. A longer duration of BMI (in kg/m 2 ) .25.0 was significantly associated with pancreatic cancer (overall HR per 10-y increment of duration: 1.06; 95% CI: 1.02, 1.09), with individuals who reported diabetes having the greatest risk (HR per 10-y increment of duration: 1.18; 95% CI: 1.05, 1.32; P-interaction = 0.01) and rates. A substantial gain in adiposity (.10 kg/m 2 ) after age 50 y was significantly associated with increased pancreatic cancer risk. The etiologic fraction of pancreatic cancer explained by adiposity at any age was 14% overall and 21% in never smokers. Conclusion: Overweight and obesity at any age are associated with increased pancreatic cancer.Am J Clin Nutr 2013;98:1057-65.

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“…Experimental studies have demonstrated that insulin may have growth-promoting effects on pancreatic ductal adenocarcinoma cells (Fisher et al, 1996;Wang et al, 1998;Ding et al, 2000) and that peripheral insulin resistance promotes pancreatic ductal carcinogenesis (Bell et al, 1988;Schneider et al, 2001). Additionally, treatment with metformin, an oral hypoglycemic agent that leads to decreases in peripheral insulin resistance and pancreatic insulin production, may prevent the development of malignant lesions (Schneider et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

Circulating insulin-like growth factor axis and the risk of pancreatic cancer in four prospective cohorts

et al. 2007

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Insulin-like growth factor (IGF)-I induces growth in pancreatic cancer cells and blockade of the IGF-I receptor has antitumour activity. The association of plasma IGF-I and IGF binding protein-3 (IGFBP-3) with pancreatic cancer risk has been investigated in two small studies, with conflicting results. We conducted a nested case -control study within four large, prospective cohorts to investigate whether prediagnostic plasma levels of IGF-I, IGF-II, and IGFBP-3 were associated with pancreatic cancer risk. Plasma levels in 212 cases and 635 matched controls were compared by conditional logistic regression, with adjustment for other known pancreatic cancer risk factors. No association was observed between plasma levels of IGF-I, IGF-II, or IGFBP-3 and incident diagnosis of pancreatic cancer. Relative risks for the highest vs the lowest quartile of IGF-I, IGF-II, and IGFBP-3 were 0.94 (95% confidence interval (CI), 0.60 -1.48), 0.96 (95% CI, 0.61 -1.52), and 1.21 (95% CI, 0.75 -1.92), respectively. The relative risk for the molar ratio of IGF-I and IGFBP-3, a surrogate measure for free IGF-I, was 0.84 (95% CI, 0.54 -1.31). Additionally, no association was noted in stratified analyses or when requiring longer follow-up. In four prospective cohorts, we found no association between the risk of pancreatic cancer and prediagnostic plasma levels of IGF-I, IGF-II, or IGFBP-3.

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Influence of diabetes on susceptibility to experimental pancreatic cancer

Cited by 39 publications

References 11 publications

Induction of adenocarcinoma from hamster pancreatic islet cells treated with N-nitrosobis(2-oxopropyl)amine in vitro

Induction of adenocarcinoma from hamster pancreatic islet cells treated with N-nitrosobis(2-oxopropyl)amine in vitro

Lifetime adiposity and risk of pancreatic cancer in the NIH-AARP Diet and Health Study cohort

Circulating insulin-like growth factor axis and the risk of pancreatic cancer in four prospective cohorts

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