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

Stocks, Tanja; Rapp, Kilian; Bjørge, Tone; Manjer, Jonas; Ulmer, Hanno; Selmer, Randi; Lukanova, Annekatrin; Johansen, Dorthe; Concin, Hans; Tretli, Steinar; Hallmans, Göran; Jonsson, Håkan; Stattin, Pär

doi:10.1371/journal.pmed.1000201

Cited by 214 publications

(195 citation statements)

References 42 publications

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“…Although biologically plausible, results from epidemiological studies are conflicting. The "hyperglycemia hypothesis" is supported by large inception cohort studies that demonstrate a strong relationship between elevated blood glucose and cancer incidence or mortality (24,(29)(30)(31). However, a recent meta-analysis reported a nonsignificant pooled risk ratio for cancer incidence of 0.91 (95% CI 0.79-1.05) for subjects with improved glycemic control across three trials, compared with those in the control arms of the studies, suggesting that improved glycemic control does not confer a reduced risk of cancer among diabetic patients (32).…”

Section: Comparison With the Literaturementioning

confidence: 99%

Cancer Risk Among People With Type 1 and Type 2 Diabetes: Disentangling True Associations, Detection Bias, and Reverse Causation

et al. 2014

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OBJECTIVEEvidence indicates an increased risk of certain cancers among people with type 2 diabetes. Evidence for rarer cancers and for type 1 diabetes is limited. We explored the excess risk of site-specific cancer incidence and mortality among people with type 1 and type 2 diabetes, compared with the general Australian population. RESEARCH DESIGN AND METHODSRegistrants of a national diabetes registry (953,382) between 1997 and 2008 were linked to national death and cancer registries. Standardized incidence and mortality ratios (SIRs/SMRs) are reported.

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Section: Comparison With the Literaturementioning

confidence: 99%

Cancer Risk Among People With Type 1 and Type 2 Diabetes: Disentangling True Associations, Detection Bias, and Reverse Causation

et al. 2014

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“…Several postulated DM-related mechanisms of carcinogenesis, including hyperglycemia itself and/or decreased bioactivity of insulin such as hyperinsulinemia or insulin resistance, have been controversial. 27,28 A meta-analysis of several prospective studies reported that not only higher levels of insulin and C-peptide but also higher levels of blood glucose significantly increased the risk of pancreatic and colorectal cancers. 29 But this meta-analysis had a critical limitation, in that few studies took fasting status into account.…”

Section: Discussionmentioning

confidence: 99%

Plasma insulin, C‐peptide and blood glucose and the risk of gastric cancer: The Japan Public Health Center‐based prospective study

Hidaka¹,

Sasazuki

Goto

et al. 2014

Intl Journal of Cancer

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To date, the association between diabetes mellitus (DM) and gastric cancer has been controversial, including the underlying mechanism. We investigated the association between plasma diabetic biomarkers (insulin, C-peptide, and blood glucose) and gastric cancer risk. In addition, homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of b-cell function (HOMA-b) were calculated. A total of 36,745 subjects aged 40-69 years in the Japan Public Health Center-based prospective study (JPHC) who returned the baseline questionnaire and provided blood samples were followed from 1990 to 2004. In the present analysis, 477 cases and 477 matched controls were used. The odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) for developing gastric cancer were calculated using conditional logistic regression models. Plasma insulin was positively associated with increased risk of gastric cancer; compared to tertile 1, ORs were 1.69 (95% CI 5 1.11-2.59) and 2.01 (1.19-3.38) for tertiles 2 and 3, respectively (p for trend 5 0.009). In men, Cpeptide was also positively associated with a significant risk; corresponding ORs were 1.42 (0.85-2.38) and 1.91 (1.03-3.54), respectively (p for trend 5 0.04). These findings were confirmed for blood samples from the fasting group (8 hr after a meal). Higher HOMA-IR was also associated with increased risk, whereas no association was observed for blood glucose. Our findings suggest that Japanese population with higher insulin and C-peptide levels derived from insulin resistance have an elevated risk of gastric cancer.Gastric cancer is the second leading cause of death and the fourth most common cancer in the world. 1 Although Helicobacter pylori (H. pylori) infection is well known as a major risk factor for gastric cancer, only some of the people infected with H. pylori will develop gastric cancer. Therefore, other risk factors might affect the association between H. pylori and gastric cancer occurrence.Diabetes mellitus (DM) is associated with many types of cancer, including colorectal, liver, breast, and pancreatic cancer.2 However, the association between DM and gastric cancer remains to be clarified. Some prospective studies reported that DM determined by questionnaire or medical records is positively associated with gastric cancer, 3-6 but others found a null association.7-12 However, DM can be easily misclassified when based on self-report of disease in questionnaire survey or medical records. To overcome this problem, several studies were directly based on diabetic biomarkers, such as hemoglobin A1c (HbA1c) and blood glucose, but the associations were also inconsistent in these prospective studies. [13][14][15][16]

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“…26 Stocks et al showed that the elevated blood levels of glucose were linked with increased cancer risk. 27 Yeh et al demonstrated that glucose and glycolysis-related genes participated in tumorigenesis of human colorectal cancers. 28 The levels of intermediates of glucose metabolism (citrate and lactate) were markedly lowered in serum samples from BC patients compared with those from healthy subjects, which might account for the accumulation of glucose observed in this study.…”

Section: Glucose Metabolismmentioning

confidence: 99%

NMR-based Metabolomic Analysis of Human Bladder Cancer

et al. 2012

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

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.

Cited by 214 publications

References 42 publications

Cancer Risk Among People With Type 1 and Type 2 Diabetes: Disentangling True Associations, Detection Bias, and Reverse Causation

Cancer Risk Among People With Type 1 and Type 2 Diabetes: Disentangling True Associations, Detection Bias, and Reverse Causation

Plasma insulin, C‐peptide and blood glucose and the risk of gastric cancer: The Japan Public Health Center‐based prospective study

NMR-based Metabolomic Analysis of Human Bladder Cancer

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