Prediagnostic plasma C-peptide and pancreatic cancer risk in men and women.

Department of Nutrition , Harvard University, Cambridge, Massachusetts, United States
Cancer Epidemiology Biomarkers & Prevention (Impact Factor: 4.32). 11/2007; 16(10):2101-9. DOI: 10.1158/1055-9965.EPI-07-0182
Source: PubMed

ABSTRACT Hyperinsulinemia and insulin resistance have been proposed as underlying mechanisms for the increase in pancreatic cancer among long-standing diabetics and obese individuals. An association between serum insulin levels and pancreatic cancer risk was reported in a recent study, but the population was composed of heavy smokers and their findings may not be generalizable to nonsmokers.
Pancreatic cancer cases and matched controls were obtained from four large-scale prospective cohorts to examine the association between prediagnostic plasma levels of C-peptide and insulin and pancreatic cancer. One hundred ninety-seven pancreatic cancer cases were diagnosed during a maximum of 20 years of follow-up, after excluding cases diagnosed within 2 years of blood collection or with baseline diabetes. We estimated OR and confidence intervals (CI) using conditional logistic regression with adjustment for pancreatic cancer risk factors.
Prediagnostic plasma C-peptide was positively associated with pancreatic cancer risk (OR, 1.52; 95% CI, 0.87-2.64, highest compared with the lowest quartile, P(trend) = 0.005). The association was not modified by body mass index or physical activity but seemed to be slightly stronger among never smokers than ever smokers. Fasting C-peptide and insulin were not related to pancreatic cancer; however, we observed a strong linear association for nonfasting C-peptide and pancreatic cancer (OR, 4.24; 95% CI, 1.30-13.8, highest versus lowest quartile, P(trend) < 0.001).
Based on our finding of a strong positive association with nonfasting C-peptide levels, we propose that insulin levels in the postprandial state may be the relevant exposure for pancreatic carcinogenesis; however, other studies will need to examine this possibility.

Download full-text


Available from: Michael Pollak, Jul 01, 2015
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: A substantial body of evidence links sex hormones, diet, excess body weight and physical activity to the risk of developing cancer at several sites common in affluent countries. The hypothesis that high circulating levels of insulin could be the underlying factor increasing cancer risk has been proposed. Epidemiological studies on markers of hyper-insulinaemia and cancer are reviewed and summarized. Studies of cancers of the colon and rectum, pancreas, breast, and endometrium examining the association with blood levels of C-peptide, insulin, glucose, glycated haemoglobin (HbA1c) were searched in PubMed. Multivariate, adjusted relative risks (RR) and their 95% confidence intervals were abstracted and summarized by meta-analyses. Most of the studies identified were cohorts that relied on measurements obtained at baseline or assessed in blood stored at low temperature several years before the onset of cancer. The meta-analyses showed excess risks of colorectal and pancreatic cancers associated with higher levels of circulating C-peptide/insulin and with markers of glycaemia. Significant heterogeneity was found among four epidemiological studies of endometrial cancer and C-peptide giving a summary RR compatible with no association. Overall breast cancer risk was significantly higher in the upper categories of C-peptide/insulin, however, the excess derived entirely from retrospective studies. Current evidence suggests that subjects who develop colorectal and pancreatic cancers have increased pre-diagnostic blood levels of insulin and glucose.
    Archives of Physiology and Biochemistry 03/2008; 114(1):63-70. DOI:10.1080/13813450801954451
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Sun exposure has been associated with lower death rates for pancreatic cancer in ecological studies. Skin exposure to solar ultraviolet B radiation induces cutaneous production of precursors to 25-hydroxy (OH) vitamin D (D) and is considered the primary contributor to vitamin D status in most populations. Pancreatic islet and duct cells express 25-(OH) D(3)-1alpha-hydroxylase that generates the biologically active 1,25-dihydroxy(OH)(2) D form. Thus, 25(OH)D concentrations could affect pancreatic function and possibly pancreatic cancer etiology. Serum 25-(OH)D is the major circulating vitamin D metabolite and is considered the best indicator of vitamin D status as determined by the sun and diet. Although recent prospective epidemiologic studies of higher predicted vitamin D status score and vitamin D intake and pancreatic cancer risk suggest protective associations, a nested case-control study showed a significant 3-fold increased risk for pancreatic cancer with higher vitamin D status. Limitations of these studies include the former do not measure vitamin D status on pancreatic cancer cases and the later was conducted in a male smoker population. More research is needed, particularly examination of pre-diagnostic vitamin D status and risk of pancreatic cancer, prior to conclusions for vitamin D's potential role in the etiology of this highly fatal cancer.
    Annals of epidemiology 06/2008; 19(2):89-95. DOI:10.1016/j.annepidem.2008.03.010 · 2.15 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Diabetes mellitus is a common disease among patients with pancreatic cancer and chronic pancreatitis, disorders of the exocrine pancreas. Different clinical features of diabetes are associated with these two conditions: hyperinsulinemia and peripheral insulin resistance are the prevailing diabetic traits in pancreatic cancer, whereas reduced islet cell mass and impaired insulin secretion are typically observed in chronic pancreatitis. Whether or not a causal relationship exists between diabetes and pancreatic carcinoma is an intriguing but unanswered question. Diabetes often precedes pancreatic cancer and is thus regarded as a potential risk factor for malignancy. Conversely, pancreatic cancer may secrete diabetogenic factors. Given these findings, there is increasing interest in whether close monitoring of the glycemic profile may aid early detection of pancreatic tumor lesions.
    Experimental and Clinical Endocrinology & Diabetes 09/2008; 116 Suppl 1:S7-S12. DOI:10.1055/s-2008-1080918 · 1.76 Impact Factor