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Prospective Study of Hyperglycemia and Cancer Risk

Response to Stattin et al.

¹ School of Public Health, University of Alberta, Edmonton, Alberta, Canada
² Institute of Health Economics, Edmonton, Alberta, Canada

Address correspondence to Dr. Jeffrey A. Johnson, # 1200, 10405 Jasper Ave., Edmonton, Alberta, T5J 3N4 Canada. E-mail: jeff.johnson{at}ualberta.ca

The recent article by Stattin et al. (1) examined whether hyperglycemia was associated with an increased risk of cancer. Using the Västerbotten Intervention Project of northern Sweden, the authors calculated relative risks of incident cancer for levels of fasting and postload glucose. They observed an association between hyperglycemia and total cancer risk in women and men for several cancer sites, suggesting that their results provide further evidence for an association between abnormal glucose levels and risk of cancer.

While the evidence is compelling, we wondered to what extent the authors might have considered potential confounding factors in the observed relationship. It is quite likely that elevated glucose levels are secondary to insulin resistance (2,3) and the resultant hyperinsulinemic state. It is likely that hyperinsulinemia may be the risk factor, or potentially a mechanism, of increased cancer rates in this group of individuals. This relationship has been confirmed in a number of studies (2,3). The authors do not mention the potential hypothesis of hyperinsulinemia and cancer risk in their article (1). We wondered whether they have information on circulating insulin levels in the sample to potentially test this hypothesis.

We also wondered how many individuals went on to develop type 2 diabetes throughout the duration of follow-up. Furthermore, it would be interesting to consider how many patients went on oral hypoglycemic agents or exogenous insulin. Recent research, including our own work, has suggested a link between antidiabetic therapies in patients with type 2 diabetes and cancer (4,5). We observed an increased risk of cancer-related mortality in patients with type 2 diabetes who used sulfonylureas compared with metformin and also an increased risk with exogenous insulin use (4). Similarly, Evans et al. (5) found a decreased risk of cancer in diabetic patients who used metformin compared with insulin secretagoues. These epidemiologic associations are supported by basic research, which suggests a mitogenic effect of insulin (6) and a protective effect of metformin (7). It might, therefore, be interesting for Stattin et al. to consider these potential confounders in their assessment of hyperglycemia as a risk factor for the incidence of cancer.

References

1. Stattin P, Bjor O, Ferrari P, Lukanova A, Lenner P, Lindahl B, Hallmans G, Kaaks R: Prospective study of hyperglycemia and cancer risk. Diabetes Care 30:561–567, 2007[Abstract/Free Full Text]
   
2. Giovannucci E: Insulin and colon cancer. Cancer Causes Control 6:164–179, 1995[Medline]
   
3. Rosenfeld RG: Insulin-like growth factors and the basis of growth. N Engl J Med 349:218–216, 2003
   
4. 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 29:254–258, 2006[Abstract/Free Full Text]
   
5. Evans JMM, Donnelly LA, Emslie-Smith AM, Alessi DR, Morris AD: Metformin and reduced risk of cancer in diabetic patients. BMJ 330:1304–1305, 2005[Free Full Text]
   
6. Van der Burg BB, Rutterman GR, Blankenstein MA, et al: Mitogenic stimulation of human breast cancer cells in a growth-defined medium: Synergistic action of insulin and estrogen. J Cell Physiol 134:101–108, 1988[Medline]
   
7. Zakikhani M, Dowling R, Fantus IG, Sonenberg N, Pollak M: Metformin is an AMP kinase-dependent growth inhibitor for breast cancer cells. Cancer Res 66:10269–73, 2006[Abstract/Free Full Text]
   

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				P. Stattin, A. Lukanova, B. Lindahl, G. Hallmans, and R. Kaaks Prospective Study of Hyperglycemia and Cancer Risk: Response to Bowker and Johnson Diabetes Care, July 1, 2007; 30(7): e78 - e78. [Full Text] [PDF]

This Article Extract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bowker, S. L. Articles by Johnson, J. A. Search for Related Content PubMed PubMed Citation Articles by Bowker, S. L. Articles by Johnson, J. A. Social Bookmarking                What's this?