Diabetes and cancer risk: A Mendelian randomization study

Atsushi Goto, Taiki Yamaji, Norie Sawada, Yukihide Momozawa, Yoichiro Kamatani, Michiaki Kubo, Taichi Shimazu, Manami Inoue, Mitsuhiko Noda, Shoichiro Tsugane, Motoki Iwasaki

Research output: Contribution to journalArticle

Abstract

Earlier cohort studies using conventional regression models have consistently shown an increased cancer risk among individuals with type 2 diabetes. However, reverse causality and residual confounding due to common risk factors could exist, and it remains unclear whether diabetes per se contributes to cancer development. Mendelian randomization analyses might clarify the true association between diabetes and cancer risk. We conducted a case–cohort study with 10,536 subcohort subjects and 3,541 newly diagnosed cancer cases derived from 32,949 eligible participants aged 40–69 years within the Japan Public Health Center-based Prospective Study. With 29 known type 2 diabetes susceptibility variants, we used an inverse variance-weighted method to estimate hazard ratios for the associations of diabetes with risks of total and site-specific cancers. The hazard ratios of cancer per doubling of the probability of diabetes were 1.03 (95% confidence interval [CI], 0.92–1.15) overall, 1.08 (95% CI: 0.73–1.59) for the pancreas, 0.80 (95% CI: 0.57–1.14) for the liver and 0.90 (95% CI: 0.74–1.10) for the colorectum. Additional analyses, using publicly available large-scale genome-wide association study data on colorectal cancer in Japan, resulted in a narrower CI (hazard ratio: 1.00; 95% CI: 0.93–1.07). In this prospective Mendelian randomization study with a large number of incident cancer cases, we found no strong evidence to support associations between diabetes and overall and site-specific cancer risks. Our findings suggest that there is little evidence to support the genetic role of type 2 diabetes in cancer development in the Japanese population.

Original languageEnglish
JournalInternational Journal of Cancer
DOIs
Publication statusPublished - 01-01-2019

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Random Allocation
Confidence Intervals
Neoplasms
Type 2 Diabetes Mellitus
Mendelian Randomization Analysis
Japan
Genome-Wide Association Study
Causality
Pancreas
Colorectal Neoplasms
Cohort Studies
Public Health
Prospective Studies
Liver

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Goto, A., Yamaji, T., Sawada, N., Momozawa, Y., Kamatani, Y., Kubo, M., ... Iwasaki, M. (2019). Diabetes and cancer risk: A Mendelian randomization study. International Journal of Cancer. https://doi.org/10.1002/ijc.32310
Goto, Atsushi ; Yamaji, Taiki ; Sawada, Norie ; Momozawa, Yukihide ; Kamatani, Yoichiro ; Kubo, Michiaki ; Shimazu, Taichi ; Inoue, Manami ; Noda, Mitsuhiko ; Tsugane, Shoichiro ; Iwasaki, Motoki. / Diabetes and cancer risk : A Mendelian randomization study. In: International Journal of Cancer. 2019.
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Goto, A, Yamaji, T, Sawada, N, Momozawa, Y, Kamatani, Y, Kubo, M, Shimazu, T, Inoue, M, Noda, M, Tsugane, S & Iwasaki, M 2019, 'Diabetes and cancer risk: A Mendelian randomization study', International Journal of Cancer. https://doi.org/10.1002/ijc.32310

Diabetes and cancer risk : A Mendelian randomization study. / Goto, Atsushi; Yamaji, Taiki; Sawada, Norie; Momozawa, Yukihide; Kamatani, Yoichiro; Kubo, Michiaki; Shimazu, Taichi; Inoue, Manami; Noda, Mitsuhiko; Tsugane, Shoichiro; Iwasaki, Motoki.

In: International Journal of Cancer, 01.01.2019.

Research output: Contribution to journalArticle

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T1 - Diabetes and cancer risk

T2 - A Mendelian randomization study

AU - Goto, Atsushi

AU - Yamaji, Taiki

AU - Sawada, Norie

AU - Momozawa, Yukihide

AU - Kamatani, Yoichiro

AU - Kubo, Michiaki

AU - Shimazu, Taichi

AU - Inoue, Manami

AU - Noda, Mitsuhiko

AU - Tsugane, Shoichiro

AU - Iwasaki, Motoki

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