Diabetes is associated with increased liver cancer incidence and mortality in adults: A report from Asia Cohort Consortium

Author:

Ho Nhan Thi1ORCID,Abe Sarah Krull2ORCID,Rahman Md. Shafiur23ORCID,Islam Rashedul24ORCID,Saito Eiko5ORCID,Gupta Prakash C.6,Pednekar Mangesh S.6,Sawada Norie7ORCID,Tsugane Shoichiro78,Tamakoshi Akiko9,Kimura Takashi9,Shu Xiao‐Ou10ORCID,Gao Yu‐Tang11,Koh Woon‐Puay1213,Cai Hui10,Wen Wanqing10,Sakata Ritsu14,Tsuji Ichiro15,Malekzadeh Reza16,Pourshams Akram17,Kanemura Seiki15,Kim Jeongseon18ORCID,Chen Yu19,Ito Hidemi2021ORCID,Oze Isao20ORCID,Nagata Chisato22,Wada Keiko22ORCID,Sugawara Yumi23ORCID,Park Sue K.24ORCID,Shin Aesun2425ORCID,Yuan Jian‐Min2627ORCID,Wang Renwei28,Kweon Sun‐Seog29,Shin Min‐Ho29,Poustchi Hossein30,Vardanjani Hossein Molavi31,Ahsan Habibul32,Chia Kee Seng33,Matsuo Keitaro3435ORCID,Qiao You‐Lin36ORCID,Rothman Nathaniel37ORCID,Zheng Wei38ORCID,Inoue Manami2ORCID,Kang Daehee39ORCID,Boffetta Paolo4041ORCID

Affiliation:

1. Research Management Department Vinmec Healthcare System Hanoi Vietnam

2. Division of Prevention National Cancer Center Institute for Cancer Control Tokyo Japan

3. Research Center for Child Mental Development Hamamatsu University School of Medicine Hamamatsu Japan

4. Hitotsubashi Institute for Advanced Study Hitotsubashi University Tokyo Japan

5. Institute for Global Health Policy Research National Center for Global Health and Medicine Tokyo Japan

6. Healis—Sekhsaria Institute for Public Health Navi Mumbai India

7. Division of Cohort Research National Cancer Center Institute for Cancer Control Tokyo Japan

8. Graduate School of Public Health International University of Health and Welfare Tokyo Japan

9. Department of Public Health Hokkaido University Faculty of Medicine Sapporo Japan

10. Division of Epidemiology, Department of Medicine Vanderbilt Epidemiology Center, Vanderbilt‐Ingram Cancer Center, Vanderbilt University Medical Center Nashville Tennessee USA

11. Department of Epidemiology Shanghai Cancer Institute Renji Hospital, Shanghai Jiaotong University School of Medicine Shanghai China

12. Healthy Longevity Translational Research Program, Yong Loo Lin School of Medicine National University of Singapore Singapore Singapore

13. Singapore Institute for Clinical Sciences Agency for Science Technology and Research (A*STAR) Singapore Singapore

14. Radiation Effects Research Foundation Hiroshima Japan

15. Tohoku University Graduate School of Medicine Sendai Japan

16. Digestive Oncology Research Center, Digestive Diseases Research Institute Tehran University of Medical Sciences Tehran Iran

17. Digestive Diseases Research Institute Tehran University of Medical Sciences Tehran Iran

18. Graduate School of Cancer Science and Policy National Cancer Center Goyang‐si South Korea

19. Department of Population Health and Environmental Medicine New York University New York New York USA

20. Division of Cancer Information and Control, Department of Preventive Medicine Aichi Cancer Center Research Institute Nagoya Japan

21. Division of Descriptive Cancer Epidemiology Nagoya University Graduate School of Medicine Nagoya Japan

22. Department of Epidemiology and Preventive Medicine Gifu University Graduate School of Medicine Gifu Japan

23. Department of Health Informatics and Public Health, Division of Epidemiology Tohoku University Graduate School of Public Health Sendai Japan

24. Department of Preventive Medicine Seoul National University College of Medicine Seoul Republic of Korea

25. Cancer Research Institute Seoul National University Seoul Republic of Korea

26. Division of Cancer Control and Population Sciences UPMC Hillman Cancer Center, University of Pittsburgh Pittsburgh Pennsylvania USA

27. Department of Epidemiology Graduate School of Public Health, University of Pittsburgh Pittsburgh Pennsylvania USA

28. Division of Cancer Control and Population Sciences UPMC Hillman Cancer Center University of Pittsburgh Pittsburgh Pennsylvania USA

29. Department of Preventive Medicine Chonnam National University Medical School Gwangju Republic of Korea

30. Digestive Disease Research institute Tehran University of Medical Science Tehran Iran

31. MD‐MPH Dual Degree Program, School of Medicine, Research Center for Traditional Medicine and History of Medicine Shiraz University of Medical Science Shiraz Iran

32. Department of Public Health Sciences University of Chicago Chicago Illinois USA

33. Saw Swee Hock School of Public Health National University of Singapore Singapore Singapore

34. Division of Cancer Epidemiology and Prevention Aichi Cancer Center Research Institute Nagoya Japan

35. Department of Cancer Epidemiology Nagoya University Graduate School of Medicine Nagoya Japan

36. School of Population Medicine and Public Health Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China

37. Division of Cancer Epidemiology and Genetics Occupational and Environmental Epidemiology Branch, National Cancer Institute Bethesda Maryland USA

38. Division of Epidemiology Vanderbilt‐Ingram Cancer Center, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center Nashville Tennessee USA

39. Seoul National University College of Medicine Seoul Republic of Korea

40. Stony Brook Cancer Center, Stony Brook University New York New York USA

41. Department of Medical and Surgical Sciences University of Bologna Bologna Italy

Abstract

AbstractThere has been growing evidence suggesting that diabetes may be associated with increased liver cancer risk. However, studies conducted in Asian countries are limited. This project considered data of 968,738 adults pooled from 20 cohort studies of Asia Cohort Consortium to examine the association between baseline diabetes and liver cancer incidence and mortality. Cox proportional hazard model and competing risk approach was used for pooled data. Two‐stage meta‐analysis across studies was also done. There were 839,194 subjects with valid data regarding liver cancer incidence (5654 liver cancer cases [48.29/100,000 person‐years]), follow‐up time and baseline diabetes (44,781 with diabetes [5.3%]). There were 747,198 subjects with valid data regarding liver cancer mortality (5020 liver cancer deaths [44.03/100,000 person‐years]), follow‐up time and baseline diabetes (43,243 with diabetes [5.8%]). Hazard ratio (HR) (95% confidence interval [95%CI]) of liver cancer diagnosis in those with vs. without baseline diabetes was 1.97 (1.79, 2.16) (p < .0001) after adjusting for baseline age, gender, body mass index, tobacco smoking, alcohol use, and heterogeneity across studies (n = 586,072; events = 4620). Baseline diabetes was associated with increased cumulative incidence of death due to liver cancer (adjusted HR (95%CI) = 1.97 (1.79, 2.18); p < .0001) (n = 595,193; events = 4110). A two‐stage meta‐analytic approach showed similar results. This paper adds important population‐based evidence to current literature regarding the increased incidence and mortality of liver cancer in adults with diabetes. The analysis of data pooled from 20 studies of different Asian countries and the meta‐analysis across studies with large number of subjects makes the results robust.

Funder

School of Medicine and Health Sciences, George Washington University

Cancer Research UK Manchester Centre

Office of Patient Care Services, Department of Veterans Affairs

JACC

Lithic Studies Society

Publisher

Wiley

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