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Cited by 562Metabolism, Diabetes, and CancerCancer Risks and FactorsPancreatic and Hepatic Oncology Research

Diabetes Mellitus and the Risk of Cancer: Results From a Large-Scale Population-Based Cohort Study in Japan

Inoue, Manami·2006·Archives of Internal Medicine
DOI 10.1001/archinte.166.17.1871
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Abstract

BACKGROUND: An association between diabetes mellitus (DM) and cancer has long been speculated, but no conclusive evidence has been obtained. METHODS: We prospectively examined the association between a history of DM and subsequent risk of cancer in the Japan Public Health Center-Based Prospective Study. A total of 97 771 general Japanese persons (46 548 men and 51 223 women) aged 40 to 69 years who responded to the baseline questionnaire, from January 1990 to December 1994, were followed up for cancer incidence through December 31, 2003. At baseline, 6.7% of men and 3.1% of women had a history of DM. RESULTS: A total of 6462 cases of newly diagnosed cancer were identified. In men, a 27% increase in the risk of total cancer incidence was observed in those with a history of DM (n = 3907 [366 with DM]; hazard ratio [HR], 1.27; 95% confidence interval [CI], 1.14-1.42). The HR was especially high for those with cancer of the liver (n = 312 [52 with DM]; HR, 2.24; 95% CI, 1.64-3.04), pancreas (n = 118 [16 with DM]; HR, 1.85; 95% CI, 1.07-3.20), and kidney (n = 99 [13 with DM]; HR, 1.92; 95% CI, 1.06-3.46). We also observed a moderately increased risk of colon cancer (n = 491 [46 with DM]; HR, 1.36; 95% CI, 1.00-1.85) and of stomach cancer with borderline significance (n = 977 [87 with DM]; HR, 1.23; 95% CI, 0.98-1.54). In women, a borderline significant increase in risk was observed for the incidence of total cancer (n = 2555 [104 with DM]; HR, 1.21; 95% CI, 0.99-1.47), while statistical significance was observed for the incidence of stomach cancer (n = 362 [20 with DM]; HR, 1.61; 95% CI, 1.02-2.54) and liver cancer (n = 120 [10 with DM]; HR, 1.94; 95% CI, 1.00-3.73) and borderline significance was observed for the incidence of ovarian cancer (n = 74 [5 with DM]; HR, 2.42; 95% CI, 0.96-6.09). CONCLUSION: Patients with DM drawn from the general Japanese population may be at increased risk of total cancer and of cancer in specific sites.

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  • The underlying mechanisms of tumorigenesis in type 2 diabetes seem related to insulin resistance, hyperinsulinemia, elevated IGF-1, and hyperglycemia driving ATP production in cancer cells through the glycolytic pathway (Warburg effect).

    “The underlying mechanisms of tumorigenesis in T2DM seem to be related to insulin resistance, hyperinsulinemia, elevated levels of IGF-1 [140-142], and hyperglycemia with the latter driving ATP production in cancer cells through the glycolytic pathway, a mechanism known as the Warburg effect [142].”

    From Metformin: An Old But Still the Best Treatment for Type 2 Diabetes (2013) · cites this paper as [140]

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Authors
Inoue, M.
Affiliations
National Cancer Centre Japan (JP)
Corresponding author
Inoue, Manami
ORCID
Inoue, Manami
Venue
Archives of Internal Medicine
Publisher
American Medical Association (AMA)
Published
2006-09-25
Volume
166
Issue
17
Pages
1871
ISSN
0003-9926 (ISSN-L)
DOI
10.1001/archinte.166.17.1871
OpenAlex
W2096623507
Cited by
561
References
59
Citations by year
2026: 3 · 2025: 6 · 2024: 20 · 2023: 21 · 2022: 29 · 2021: 24 · 2020: 28 · 2019: 29 · 2018: 22 · 2017: 35 · 2016: 22 · 2015: 31 · 2014: 41 · 2013: 51 · 2012: 55
FWCI
6.75
Type
journal article
Language
en
Open access
closed
Locations
  • Archives of Internal Medicine (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
  • Health Sciences › Medicine › Oncology › Cancer Risks and Factors
  • Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
Keywords
diabetes mellitus, cancer risk, cancer incidence, liver cancer, pancreatic cancer, kidney cancer, colon cancer, gastric cancer, sex differences, Japan Public Health Center-based Prospective Study, Japanese adults, prospective cohort, hazard ratio, cancer mortality, cancer prevention, lifestyle modification, cancer survivorship, cancer survivorship support services
MeSH terms
Adult, Aged, Diabetes Mellitus, Digestive System Neoplasms, Female, Humans, Japan, Male, Middle Aged, Neoplasms, Prospective Studies, Risk Factors, Incidence, Diabetes Complications

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