Research Article: Blood Glucose and Risk of Incident and Fatal Cancer in the Metabolic Syndrome and Cancer Project (Me-Can): Analysis of Six Prospective Cohorts

Date Published: December 22, 2009

Publisher: Public Library of Science

Author(s): Tanja Stocks, Kilian Rapp, Tone Bjørge, Jonas Manjer, Hanno Ulmer, Randi Selmer, Annekatrin Lukanova, Dorthe Johansen, Hans Concin, Steinar Tretli, Göran Hallmans, Håkan Jonsson, Pär Stattin, Nicholas J. Wareham

Abstract: Tanja Stocks and colleagues carry out an analysis of six European cohorts and confirm that abnormal glucose metabolism is linked with increased risk of cancer overall and at specific sites.

Partial Text: Elevated blood glucose has been associated with an increased risk of cancer overall in several prospective studies [1]–[6]. The strongest evidence comes from a Korean cohort study of 1.3 million men and women that reported an increased risk of incident as well as of fatal cancer in individuals with high glucose levels [1]. Prospective studies of glucose and cancer risk in cohorts of European and US populations have been much smaller, and these studies did not concurrently report on risk of incident and fatal cancer [2]–[7]. Previous results from cohorts in Austria [2] and Sweden [3] included in the current study, also indicated that elevated fasting glucose is related to an increased risk of overall incident cancer. However, the relatively modest sample size in these studies resulted in limited power to estimate risks for individual cancer sites. Furthermore, exposure assessment by glucose measurement at a single occasion entails a substantial random error owing to technical measurement error and within-person variation of blood glucose level [8],[9]. Such inaccuracy of exposure assessment will dilute the association with outcome, i.e., regression dilution bias [8],[10],[11]. In several prospective studies of metabolic factors and risk of cardiovascular disease, data from multiple examinations have been used to correct risk estimates for random error in exposure classification, which resulted in substantially stronger associations than estimates on the basis of uncorrected exposures [12]–[14]. To date, correction for random error has only been performed in one study on glucose and cancer risk [3].

In this large prospective cohort study, elevated blood glucose was significantly associated with an increased risk of incident and fatal cancer at all sites combined, and of several specific cancers. In women, a linear association between glucose and risk of overall incident and fatal cancer was observed, and levels within the upper normal range were also related to increases in risk. In men, the association between glucose and total incident cancer was somewhat weaker, and risk of fatal cancer was only significantly increased at levels approximately equivalent to impaired glucose levels. Women in the top glucose decile had twice the risk of fatal cancer compared to women with glucose levels below the 40th percentile and the risk increase among men in the top decile was almost the same. Risk estimates were obtained after correction for random error in glucose levels, which was high in our study in accordance with previous observations [3],[8],[9]. The estimates of excess risk of fatal cancer in the top decile corrected for regression dilution were 4-fold higher than the uncorrected estimates. These data indicate that in previous analyses without such correction, risk estimates for increasing glucose may have been underestimated [1]–[7].



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