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Type 2 diabetes, glycaemic traits and upper gastrointestinal cancer risk: a prospective cohort study
  1. Luyao Cao1,
  2. Tianpei Wang1,2,3,
  3. Huizhang Li4,
  4. Fadoua El Hafa1,
  5. Xia Zhu1,
  6. Yuhui Yu1,
  7. Caiwang Yan1,2,
  8. Lingbin Du4,
  9. Meng Zhu1,2,5,
  10. Guangfu Jin1,2,5
  1. 1Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China
  2. 2Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine and China International Cooperation Center for Environment and Human Health, Nanjing Medical University, Nanjing, Jiangsu, China
  3. 3Health Management Center, The First Affiliated Hospital With Nanjing Medical University, Nanjing, Jiangsu, China
  4. 4Zhejiang Provincial Office for Cancer Prevention and Control, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China
  5. 5The Affiliated Wuxi Center for Disease Control and Prevention of Nanjing Medical University, Wuxi Center for Disease Control and Prevention, Wuxi Medical Center, Nanjing Medical University, Wuxi, Jiangsu, China
  1. Correspondence to Professor Guangfu Jin, Department of Epidemiology, Nanjing Medical University, Nanjing, Jiangsu 211166, China; guangfujin{at}njmu.edu.cn; Dr Meng Zhu, Department of Epidemiology, Nanjing Medical University, Nanjing, Jiangsu 211166, China; zhmnjmu{at}njmu.edu.cn; Lingbin Du, Zhejiang Provincial Office for Cancer Prevention and Control, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310005, China; dulb{at}zjcc.org.cn

Abstract

Background Type 2 diabetes (T2D) has been linked with site-specific upper gastrointestinal (UGI) cancers during the past decades, but associations are still inconclusive. This study aimed to determine the association between T2D, glycaemic traits (random blood glucose and HbA1c) and UGI cancer (oesophageal and gastric cancer).

Methods In the present study, based on the large-scale prospective cohort of UK Biobank, we included 452 631 eligible participants. T2D was defined according to baseline self-report data, clinical data and biochemistry data. Random blood glucose and HbA1c were measured at baseline. Polygenic risk score was used to classify individuals into different UGI cancer genetic risks. Multivariable Cox regression models were used to estimate HRs and 95% CIs.

Results During a median follow-up of 10.26 years (IQR: 9.47–10.97), 1392 incident UGI cancer cases were identified. T2D was significantly associated with a 44% increment in UGI cancer risk (95% CI 1.22 to 1.70, p<0.001). Moreover, per SD increase in random blood glucose and HbA1c was associated with 7% (95% CI 1.03 to 1.12, p<0.001) and 6% (95% CI 1.04 to 1.09, p<0.001) increased hazards of developing UGI cancer, respectively. Patients with T2D at high genetic risk had a 2.33-fold hazard of UGI cancer (95% CI 1.66 to 3.28, p<0.001), compared with non-T2D individuals at low genetic risk.

Conclusion Our results indicate that T2D and elevated levels of glycaemic traits may be risk factors for incident UGI cancer. Individuals with a high genetic risk and T2D have a significantly increased risk of developing UGI cancer.

  • DIABETES MELLITUS
  • EPIDEMIOLOGY
  • GASTROENTEROLOGY

Data availability statement

Data may be obtained from a third party and are not publicly available. Information about data access is available at https://biobank.ndph.ox.ac.uk/ukb/.

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Data availability statement

Data may be obtained from a third party and are not publicly available. Information about data access is available at https://biobank.ndph.ox.ac.uk/ukb/.

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Footnotes

  • LC, TW and HL are joint first authors.

  • Contributors Conceptualisation: LC, MZ and GJ. Methodology: LC and TW. Formal analysis and investigation: LC and TW. Writing—original draft preparation: LC. Writing—review and editing: LC, TW, HL, LD, MZ and GJ. Data acquisition or interpretation: LC, TW, HL, FEH, YY, XZ, CY, LD, MZ and GJ. All authors have read and approved the publication of the final manuscript. GJ is responsible for the overall content as the guarantor.

  • Funding This research was supported by the National Natural Science Foundation of China (82230110, 82125033, 82273714, 82003534); the Excellent Youth Foundation of Jiangsu Province (BK20220100); and the Natural Science Foundation of Jiangsu Province (BK20200674).

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.