Skip to main content
Top
Published in: Cancer Causes & Control 5/2009

01-07-2009 | Original Paper

Metabolic factors and subsequent risk of hepatocellular carcinoma by hepatitis virus infection status: a large-scale population-based cohort study of Japanese men and women (JPHC Study Cohort II)

Authors: Manami Inoue, Norie Kurahashi, Motoki Iwasaki, Yasuhito Tanaka, Masashi Mizokami, Mitsuhiko Noda, Shoichiro Tsugane, for the Japan Public Health Center-based Prospective Study Group

Published in: Cancer Causes & Control | Issue 5/2009

Login to get access

Abstract

Objective

The association between metabolic factors and hepatocellular carcinoma (HCC) has not been well clarified. We prospectively examined whether metabolic factors predicts the subsequent risk of HCC in the Japan Public Health Center-based Prospective Study Cohort II, in consideration of hepatitis virus infection status.

Methods

A total of 17,590 subjects aged 40–69 participating in a questionnaire and health checkup survey during 1993–1994 were followed for incidence of HCC through 2006. A total of 102 cases of HCC were newly documented. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for metabolic factors controlling for potential confounding factors.

Results

The presence of metabolic factors in the aggregate was associated with a significantly increased risk of HCC, especially with hepatitis virus infection. HCC was positively associated particularly with high glucose (HR = 1.75, CI = 1.11–2.74) and overweight (HR = 2.22, CI = 1.42–3.48). Results were similar when analyses were limited to subjects with HCV infection.

Conclusions

Although metabolic factors in the aggregate may be associated with an increased risk of HCC, the main contributors to this association under HCV infection appear to be overweight and high glucose. Improvement of these factors may be a crucial target in preventing progression to HCC in those with HCV infection.
Appendix
Available only for authorised users
Literature
5.
go back to reference El-Serag HB, Hampel H, Javadi F (2007) The Editorial Board of the Cancer Statistics in Japan. Cancer statistics in Japan 2007. Foundation for Promotion of Cancer Research (FPFR), Tokyo El-Serag HB, Hampel H, Javadi F (2007) The Editorial Board of the Cancer Statistics in Japan. Cancer statistics in Japan 2007. Foundation for Promotion of Cancer Research (FPFR), Tokyo
6.
go back to reference Marugame T, Matsuda T, Kamo K, Katanoda K, Ajiki W, Sobue T (2007) Cancer incidence and incidence rates in Japan in 2001 based on the data from 10 population-based cancer registries. Jpn J Clin Oncol 37:884–891. doi:10.1093/jjco/hym112 PubMedCrossRef Marugame T, Matsuda T, Kamo K, Katanoda K, Ajiki W, Sobue T (2007) Cancer incidence and incidence rates in Japan in 2001 based on the data from 10 population-based cancer registries. Jpn J Clin Oncol 37:884–891. doi:10.​1093/​jjco/​hym112 PubMedCrossRef
7.
go back to reference Shiratori Y, Shiina S, Imamura M, Kato N, Kanai F, Okudaira T, Teratani T, Tohgo G, Toda N, Ohashi M et al (1995) Characteristic difference of hepatocellular carcinoma between hepatitis B- and C-viral infection in Japan. Hepatology 22:1027–1033PubMedCrossRef Shiratori Y, Shiina S, Imamura M, Kato N, Kanai F, Okudaira T, Teratani T, Tohgo G, Toda N, Ohashi M et al (1995) Characteristic difference of hepatocellular carcinoma between hepatitis B- and C-viral infection in Japan. Hepatology 22:1027–1033PubMedCrossRef
10.
go back to reference Chen CL, Yang HI, Yang WS, Liu CJ, Chen PJ, You SL, Wang LY, Sun CA, Lu SN, Chen DS, Chen CJ (2008) Metabolic factors and risk of hepatocellular carcinoma by chronic hepatitis B/C infection: a follow-up study in Taiwan. Gastroenterology 135:111–121. doi:10.1053/j.gastro.2008.03.073 PubMedCrossRef Chen CL, Yang HI, Yang WS, Liu CJ, Chen PJ, You SL, Wang LY, Sun CA, Lu SN, Chen DS, Chen CJ (2008) Metabolic factors and risk of hepatocellular carcinoma by chronic hepatitis B/C infection: a follow-up study in Taiwan. Gastroenterology 135:111–121. doi:10.​1053/​j.​gastro.​2008.​03.​073 PubMedCrossRef
13.
go back to reference Lai MS, Hsieh MS, Chiu YH, Chen TH (2006) Type 2 diabetes and hepatocellular carcinoma: a cohort study in high prevalence area of hepatitis virus infection. Hepatology 43:1295–1302. doi:10.1002/hep.21208 PubMedCrossRef Lai MS, Hsieh MS, Chiu YH, Chen TH (2006) Type 2 diabetes and hepatocellular carcinoma: a cohort study in high prevalence area of hepatitis virus infection. Hepatology 43:1295–1302. doi:10.​1002/​hep.​21208 PubMedCrossRef
15.
go back to reference Yuan JM, Govindarajan S, Arakawa K, Yu MC (2004) Synergism of alcohol, diabetes, and viral hepatitis on the risk of hepatocellular carcinoma in blacks and whites in the U.S. Cancer 101:1009–1017. doi:10.1002/cncr.20427 PubMedCrossRef Yuan JM, Govindarajan S, Arakawa K, Yu MC (2004) Synergism of alcohol, diabetes, and viral hepatitis on the risk of hepatocellular carcinoma in blacks and whites in the U.S. Cancer 101:1009–1017. doi:10.​1002/​cncr.​20427 PubMedCrossRef
16.
go back to reference Hassan MM, Hwang LY, Hatten CJ, Swaim M, Li D, Abbruzzese JL, Beasley P, Patt YZ (2002) Risk factors for hepatocellular carcinoma: synergism of alcohol with viral hepatitis and diabetes mellitus. Hepatology 36:1206–1213. doi:10.1053/jhep.2002.36780 PubMedCrossRef Hassan MM, Hwang LY, Hatten CJ, Swaim M, Li D, Abbruzzese JL, Beasley P, Patt YZ (2002) Risk factors for hepatocellular carcinoma: synergism of alcohol with viral hepatitis and diabetes mellitus. Hepatology 36:1206–1213. doi:10.​1053/​jhep.​2002.​36780 PubMedCrossRef
19.
go back to reference La Vecchia C, Negri E, Decarli A, Franceschi S (1997) Diabetes mellitus and the risk of primary liver cancer. Int J Cancer 73:204–207. doi:10.1002/(SICI)1097-0215(19971009)73:2<204::AID-IJC7>3.0.CO;2-#PubMedCrossRef La Vecchia C, Negri E, Decarli A, Franceschi S (1997) Diabetes mellitus and the risk of primary liver cancer. Int J Cancer 73:204–207. doi:10.1002/(SICI)1097-0215(19971009)73:2<204::AID-IJC7>3.0.CO;2-#PubMedCrossRef
21.
go back to reference Ohishi W, Fujiwara S, Cologne JB, Suzuki G, Akahoshi M, Nishi N, Takahashi I, Chayama K (2008) Risk factors for hepatocellular carcinoma in a Japanese population: a nested case–control study. Cancer Epidemiol Biomarkers Prev 17:846–854. doi:10.1158/1055-9965.EPI-07-2806 PubMedCrossRef Ohishi W, Fujiwara S, Cologne JB, Suzuki G, Akahoshi M, Nishi N, Takahashi I, Chayama K (2008) Risk factors for hepatocellular carcinoma in a Japanese population: a nested case–control study. Cancer Epidemiol Biomarkers Prev 17:846–854. doi:10.​1158/​1055-9965.​EPI-07-2806 PubMedCrossRef
23.
25.
go back to reference Rapp K, Schroeder J, Klenk J, Stoehr S, Ulmer H, Concin H, Diem G, Oberaigner W, Weiland SK (2005) Obesity and incidence of cancer: a large cohort study of over 145,000 adults in Austria. Br J Cancer 93:1062–1067. doi:10.1038/sj.bjc.6602819 PubMedCrossRef Rapp K, Schroeder J, Klenk J, Stoehr S, Ulmer H, Concin H, Diem G, Oberaigner W, Weiland SK (2005) Obesity and incidence of cancer: a large cohort study of over 145,000 adults in Austria. Br J Cancer 93:1062–1067. doi:10.​1038/​sj.​bjc.​6602819 PubMedCrossRef
27.
go back to reference Tsugane S, Sobue T (2001) Baseline survey of JPHC study–design and participation rate, Japan Public Health Center-based Prospective Study on Cancer and Cardiovascular Diseases. J Epidemiol 11:S24–S29PubMed Tsugane S, Sobue T (2001) Baseline survey of JPHC study–design and participation rate, Japan Public Health Center-based Prospective Study on Cancer and Cardiovascular Diseases. J Epidemiol 11:S24–S29PubMed
28.
go back to reference Iida M, Sato S, Nakamura M (2001) Standardization of laboratory test in the JPHC study, Japan Public Health Center-based Prospective Study on Cancer and Cardiovascular Diseases. J Epidemiol 11:S81–S86PubMed Iida M, Sato S, Nakamura M (2001) Standardization of laboratory test in the JPHC study, Japan Public Health Center-based Prospective Study on Cancer and Cardiovascular Diseases. J Epidemiol 11:S81–S86PubMed
29.
go back to reference Nakamura M, Sato S, Shimamoto T (2003) Improvement in Japanese clinical laboratory measurements of total cholesterol and HDL-cholesterol by the US Cholesterol Reference Method Laboratory Network. J Atheroscler Thromb 10:145–153PubMed Nakamura M, Sato S, Shimamoto T (2003) Improvement in Japanese clinical laboratory measurements of total cholesterol and HDL-cholesterol by the US Cholesterol Reference Method Laboratory Network. J Atheroscler Thromb 10:145–153PubMed
30.
go back to reference Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, Gordon DJ, Krauss RM, Savage PJ, Smith SC Jr, Spertus JA, Costa F (2005) Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation 112:2735–2752. doi:10.1161/CIRCULATIONAHA.105.169404 PubMedCrossRef Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, Gordon DJ, Krauss RM, Savage PJ, Smith SC Jr, Spertus JA, Costa F (2005) Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation 112:2735–2752. doi:10.​1161/​CIRCULATIONAHA.​105.​169404 PubMedCrossRef
32.
go back to reference Examination Committee of Criteria for ‘Obesity Disease’ in Japan; Japan Society for the Study of Obesity (2006) New criteria for ‘obesity disease’ in Japan. Circ J 66:987–992. doi:10.1253/circj.66.987 Examination Committee of Criteria for ‘Obesity Disease’ in Japan; Japan Society for the Study of Obesity (2006) New criteria for ‘obesity disease’ in Japan. Circ J 66:987–992. doi:10.​1253/​circj.​66.​987
34.
go back to reference Abdel-Hamid M, El-Daly M, El-Kafrawy S, Mikhail N, Strickland GT, Fix AD (1990) World Health Organization International classification of diseases and health related problem, 10th revision. World Health Organization, Geneva, Switzerland Abdel-Hamid M, El-Daly M, El-Kafrawy S, Mikhail N, Strickland GT, Fix AD (1990) World Health Organization International classification of diseases and health related problem, 10th revision. World Health Organization, Geneva, Switzerland
35.
go back to reference Abdel-Hamid M, El-Daly M, El-Kafrawy S, Mikhail N, Strickland GT, Fix AD (2000) World Health Organization International classification of diseases for oncology, 3rd edn. World Health Organization, Geneva, Switzerland Abdel-Hamid M, El-Daly M, El-Kafrawy S, Mikhail N, Strickland GT, Fix AD (2000) World Health Organization International classification of diseases for oncology, 3rd edn. World Health Organization, Geneva, Switzerland
36.
go back to reference Abdel-Hamid M, El-Daly M, El-Kafrawy S, Mikhail N, Strickland GT, Fix AD (2007) Stata Corporation Stata Statistical Software. Stata Corporation, College Station, TX Abdel-Hamid M, El-Daly M, El-Kafrawy S, Mikhail N, Strickland GT, Fix AD (2007) Stata Corporation Stata Statistical Software. Stata Corporation, College Station, TX
39.
go back to reference Jan CF, Chen CJ, Chiu YH, Chen LS, Wu HM, Huang CC, Yen MF, Chen TH (2006) A population-based study investigating the association between metabolic syndrome and hepatitis B/C infection (Keelung Community-based Integrated Screening study No. 10). Int J Obes (Lond) 30:794–799. doi:10.1038/sj.ijo.0803204 CrossRef Jan CF, Chen CJ, Chiu YH, Chen LS, Wu HM, Huang CC, Yen MF, Chen TH (2006) A population-based study investigating the association between metabolic syndrome and hepatitis B/C infection (Keelung Community-based Integrated Screening study No. 10). Int J Obes (Lond) 30:794–799. doi:10.​1038/​sj.​ijo.​0803204 CrossRef
40.
go back to reference Siagris D, Christofidou M, Theocharis GJ, Pagoni N, Papadimitriou C, Lekkou A, Thomopoulos K, Starakis I, Tsamandas AC, Labropoulou-Karatza C (2006) Serum lipid pattern in chronic hepatitis C: histological and virological correlations. J Viral Hepat 13:56–61. doi:10.1111/j.1365-2893.2005.00655.x PubMedCrossRef Siagris D, Christofidou M, Theocharis GJ, Pagoni N, Papadimitriou C, Lekkou A, Thomopoulos K, Starakis I, Tsamandas AC, Labropoulou-Karatza C (2006) Serum lipid pattern in chronic hepatitis C: histological and virological correlations. J Viral Hepat 13:56–61. doi:10.​1111/​j.​1365-2893.​2005.​00655.​x PubMedCrossRef
41.
go back to reference Donnelly KL, Smith CI, Schwarzenberg SJ, Jessurun J, Boldt MD, Parks EJ (2005) Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. J Clin Invest 115:1343–1351PubMed Donnelly KL, Smith CI, Schwarzenberg SJ, Jessurun J, Boldt MD, Parks EJ (2005) Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. J Clin Invest 115:1343–1351PubMed
43.
go back to reference Hatanaka K, Kudo M, Fukunaga T, Ueshima K, Chung H, Minami Y, Sakaguchi Y, Hagiwara S, Orino A, Osaki Y (2007) Clinical characteristics of NonBNonC-HCC: comparison with HBV and HCV related HCC. Intervirology 50:24–31. doi:10.1159/000096309 PubMedCrossRef Hatanaka K, Kudo M, Fukunaga T, Ueshima K, Chung H, Minami Y, Sakaguchi Y, Hagiwara S, Orino A, Osaki Y (2007) Clinical characteristics of NonBNonC-HCC: comparison with HBV and HCV related HCC. Intervirology 50:24–31. doi:10.​1159/​000096309 PubMedCrossRef
45.
go back to reference Iwasaki M, Otani T, Yamamoto S, Inoue M, Hanaoka T, Sobue T, Tsugane S (2003) Background characteristics of basic health examination participants: the JPHC Study Baseline Survey. J Epidemiol 13:216–225PubMed Iwasaki M, Otani T, Yamamoto S, Inoue M, Hanaoka T, Sobue T, Tsugane S (2003) Background characteristics of basic health examination participants: the JPHC Study Baseline Survey. J Epidemiol 13:216–225PubMed
46.
go back to reference Iwasaki M, Yamamoto S, Otani T, Inoue M, Hanaoka T, Sobue T, Tsugane S (2006) Generalizability of relative risk estimates from a well-defined population to a general population. Eur J Epidemiol 21:253–262. doi:10.1007/s10654-006-0004-z PubMedCrossRef Iwasaki M, Yamamoto S, Otani T, Inoue M, Hanaoka T, Sobue T, Tsugane S (2006) Generalizability of relative risk estimates from a well-defined population to a general population. Eur J Epidemiol 21:253–262. doi:10.​1007/​s10654-006-0004-z PubMedCrossRef
Metadata
Title
Metabolic factors and subsequent risk of hepatocellular carcinoma by hepatitis virus infection status: a large-scale population-based cohort study of Japanese men and women (JPHC Study Cohort II)
Authors
Manami Inoue
Norie Kurahashi
Motoki Iwasaki
Yasuhito Tanaka
Masashi Mizokami
Mitsuhiko Noda
Shoichiro Tsugane
for the Japan Public Health Center-based Prospective Study Group
Publication date
01-07-2009
Publisher
Springer Netherlands
Published in
Cancer Causes & Control / Issue 5/2009
Print ISSN: 0957-5243
Electronic ISSN: 1573-7225
DOI
https://doi.org/10.1007/s10552-008-9287-6

Other articles of this Issue 5/2009

Cancer Causes & Control 5/2009 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine