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) (original) (raw)

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.

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References

  1. Lonardo A, Loria P, Carulli N (2008) Dysmetabolic changes associated with HCV: a distinct syndrome? Intern Emerg Med 3:99–108. doi:10.1007/s11739-008-0127-1
    Article PubMed Google Scholar
  2. Bugianesi E (2005) Review article: steatosis, the metabolic syndrome and cancer. Aliment Pharmacol Ther 22(Suppl 2):40–43. doi:10.1111/j.1365-2036.2005.02594.x
    Article PubMed Google Scholar
  3. Bugianesi E, Zannoni C, Vanni E, Marzocchi R, Marchesini G (2004) Non-alcoholic fatty liver and insulin resistance: a cause–effect relationship? Dig Liver Dis 36:165–173. doi:10.1016/j.dld.2003.12.008
    Article PubMed CAS Google Scholar
  4. El-Serag HB, Hampel H, Javadi F (2006) The association between diabetes and hepatocellular carcinoma: a systematic review of epidemiologic evidence. Clin Gastroenterol Hepatol 4:369–380. doi:10.1016/j.cgh.2005.12.007
    Article PubMed Google Scholar
  5. 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. 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
    Article PubMed Google Scholar
  7. 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 22:1027–1033
    Article PubMed CAS Google Scholar
  8. Eckel RH, Grundy SM, Zimmet PZ (2005) The metabolic syndrome. Lancet 365:1415–1428. doi:10.1016/S0140-6736(05)66378-7
    Article PubMed CAS Google Scholar
  9. Russo A, Autelitano M, Bisanti L (2008) Metabolic syndrome and cancer risk. Eur J Cancer 44:293–297. doi:10.1016/j.ejca.2007.11.005
    Article PubMed Google Scholar
  10. 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
    Article PubMed CAS Google Scholar
  11. Inoue M, Iwasaki M, Otani T, Sasazuki S, Noda M, Tsugane S (2006) Diabetes mellitus and the risk of cancer: results from a large-scale population-based cohort study in Japan. Arch Intern Med 166:1871–1877. doi:10.1001/archinte.166.17.1871
    Article PubMed Google Scholar
  12. Kuriki K, Hirose K, Tajima K (2007) Diabetes and cancer risk for all and specific sites among Japanese men and women. Eur J Cancer Prev 16:83–89. doi:10.1097/01.cej.0000228404.37858.40
    Article PubMed Google Scholar
  13. 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
    Article PubMed Google Scholar
  14. Jee SH, Ohrr H, Sull JW, Yun JE, Ji M, Samet JM (2005) Fasting serum glucose level and cancer risk in Korean men and women. JAMA 293:194–202. doi:10.1001/jama.293.2.194
    Article PubMed CAS Google Scholar
  15. 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
    Article PubMed Google Scholar
  16. 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
    Article PubMed CAS Google Scholar
  17. El-Serag HB, Richardson PA, Everhart JE (2001) The role of diabetes in hepatocellular carcinoma: a case–control study among United States Veterans. Am J Gastroenterol 96:2462–2467. doi:10.1111/j.1572-0241.2001.04054.x
    Article PubMed CAS Google Scholar
  18. Lagiou P, Kuper H, Stuver SO, Tzonou A, Trichopoulos D, Adami HO (2000) Role of diabetes mellitus in the etiology of hepatocellular carcinoma. J Natl Cancer Inst 92:1096–1099. doi:10.1093/jnci/92.13.1096
    Article PubMed CAS Google Scholar
  19. 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-#
    Article PubMed Google Scholar
  20. Davila JA, Morgan RO, Shaib Y, McGlynn KA, El-Serag HB (2005) Diabetes increases the risk of hepatocellular carcinoma in the United States: a population based case control study. Gut 54:533–539. doi:10.1136/gut.2004.052167
    Article PubMed CAS Google Scholar
  21. 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
    Article PubMed CAS Google Scholar
  22. Samanic C, Gridley G, Chow WH, Lubin J, Hoover RN, Fraumeni JF Jr (2004) Obesity and cancer risk among white and black United States veterans. Cancer Causes Control 15:35–43. doi:10.1023/B:CACO.0000016573.79453.ba
    Article PubMed Google Scholar
  23. Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ (2003) Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med 348:1625–1638. doi:10.1056/NEJMoa021423
    Article PubMed Google Scholar
  24. Moller H, Mellemgaard A, Lindvig K, Olsen JH (1994) Obesity and cancer risk: a Danish record-linkage study. Eur J Cancer 30A:344–350. doi:10.1016/0959-8049(94)90254-2
    Article PubMed CAS Google Scholar
  25. 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
    Article PubMed CAS Google Scholar
  26. Wolk A, Gridley G, Svensson M, Nyren O, McLaughlin JK, Fraumeni JF, Adam HO (2001) A prospective study of obesity and cancer risk (Sweden). Cancer Causes Control 12:13–21. doi:10.1023/A:1008995217664
    Article PubMed CAS Google Scholar
  27. 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–S29
    PubMed CAS Google Scholar
  28. 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–S86
    PubMed CAS Google Scholar
  29. 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 10:145–153
    PubMed CAS Google Scholar
  30. 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
    Article PubMed Google Scholar
  31. Alberti KG, Zimmet P, Shaw J (2006) Metabolic syndrome—a new world-wide definition, A Consensus Statement from the International Diabetes Federation. Diabet Med 23:469–480. doi:10.1111/j.1464-5491.2006.01858.x
    Article PubMed CAS Google Scholar
  32. 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
    Google Scholar
  33. Abdel-Hamid M, El-Daly M, El-Kafrawy S, Mikhail N, Strickland GT, Fix AD (2002) Comparison of second- and third-generation enzyme immunoassays for detecting antibodies to hepatitis C virus. J Clin Microbiol 40:1656–1659. doi:10.1128/JCM.40.5.1656-1659.2002
    Article PubMed CAS Google Scholar
  34. 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
    Google Scholar
  35. 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
    Google Scholar
  36. 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
    Google Scholar
  37. Yu MC, Yuan JM (2004) Environmental factors and risk for hepatocellular carcinoma. Gastroenterology 127:S72–S78. doi:10.1016/j.gastro.2004.09.018
    Article PubMed CAS Google Scholar
  38. McIntyre N (1978) Plasma lipids and lipoproteins in liver disease. Gut 19:526–530. doi:10.1136/gut.19.6.526
    Article PubMed CAS Google Scholar
  39. 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
    Article Google Scholar
  40. 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
    Article PubMed CAS Google Scholar
  41. 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 115:1343–1351
    PubMed CAS Google Scholar
  42. Ono M, Saibara T (2006) Clinical features of nonalcoholic steatohepatitis in Japan: evidence from the literature. J Gastroenterol 41:725–732. doi:10.1007/s00535-006-1876-0
    Article PubMed Google Scholar
  43. 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
    Article PubMed Google Scholar
  44. Hashimoto E, Yatsuji S, Kaneda H, Yoshioka Y, Taniai M, Tokushige K, Shiratori K (2005) The characteristics and natural history of Japanese patients with nonalcoholic fatty liver disease. Hepatol Res 33:72–76. doi:10.1016/j.hepres.2005.09.007
    Article PubMed Google Scholar
  45. 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 13:216–225
    PubMed Google Scholar
  46. 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
    Article PubMed Google Scholar

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Aknowledgment

This study was supported by a Grant-in-Aid for Cancer Research, for Research on Hepatitis, for the Third Term Comprehensive Control Research for Cancer, and for Health Science Research from the Ministry of Health, Labour and Welfare of Japan.

Author information

Authors and Affiliations

  1. Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
    Manami Inoue, Norie Kurahashi, Motoki Iwasaki & Shoichiro Tsugane
  2. Department of Clinical Molecular Informative Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
    Yasuhito Tanaka & Masashi Mizokami
  3. Department of Diabetes and Metabolic Medicine, International Medical Center of Japan, Tokyo, Japan
    Mitsuhiko Noda

Authors

  1. Manami Inoue
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  2. Norie Kurahashi
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  3. Motoki Iwasaki
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  4. Yasuhito Tanaka
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  5. Masashi Mizokami
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  6. Mitsuhiko Noda
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  7. Shoichiro Tsugane
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Consortia

for the Japan Public Health Center-based Prospective Study Group

Corresponding author

Correspondence toManami Inoue.

Additional information

The members of the Japan Public Health Center-based Prospective Study Group are listed in Appendix.

Appendix

Appendix

Members of the Japan Public Health Center-based Prospective Study (JPHC Study, principal investigator: S. Tsugane) Group are: S. Tsugane, M. Inoue, T. Sobue, and T. Hanaoka, National Cancer Center, Tokyo; J. Ogata, S. Baba, T. Mannami, A. Okayama, and Y. Kokubo, National Cardiovascular Center, Osaka; K. Miyakawa, F. Saito, A. Koizumi, Y. Sano, I. Hashimoto, T. Ikuta, and Y. Tanaba, Iwate Prefectural Ninohe Public Health Center, Iwate; Y. Miyajima, N. Suzuki, S. Nagasawa, Y. Furusugi, and N. Nagai, Akita Prefectural Yokote Public Health Center, Akita; H. Sanada, Y. Hatayama, F. Kobayashi, H. Uchino, Y. Shirai, T. Kondo, R. Sasaki, Y. Watanabe, Y. Miyagawa, and Y. Kobayashi, Nagano Prefectural Saku Public Health Center, Nagano; Y. Kishimoto, E. Takara, T. Fukuyama, M. Kinjo, M. Irei, and H. Sakiyama, Okinawa Prefectural Chubu Public Health Center, Okinawa; K. Imoto, H. Yazawa, T. Seo, A. Seiko, F. Ito, F. Shoji, and R. Saito, Katsushika Public Health Center, Tokyo; A. Murata, K. Minato, K. Motegi, and T. Fujieda, Ibaraki Prefectural Mito Public Health Center, Ibaraki; K. Matsui, T. Abe, M. Katagiri, M. Suzuki, and K. Matsui, Niigata Prefectural Kashiwazaki and Nagaoka Public Health Center, Niigata; M. Doi, A. Terao, Y. Ishikawa, and T. Tagami, Kochi Prefectural Chuo-higashi Public Health Center, Kochi; H. Sueta, H. Doi, M. Urata, N. Okamoto, and F. Ide, Nagasaki Prefectural Kamigoto Public Health Center, Nagasaki; H. Sakiyama, N. Onga, H. Takaesu, and M. Uehara, Okinawa Prefectural Miyako Public Health Center, Okinawa; F. Horii, I. Asano, H. Yamaguchi, K. Aoki, S. Maruyama, M. Ichii, and M. Takano, Osaka Prefectural Suita Public Health Center, Osaka; Y. Tsubono, Tohoku University, Miyagi; K. Suzuki, Research Institute for Brain and Blood Vessels Akita, Akita; Y. Honda, K. Yamagishi, and S. Sakurai, Tsukuba University, Ibaraki; M. Kabuto, National Institute for Environmental Studies, Ibaraki; M. Yamaguchi, Y. Matsumura, S. Sasaki, and S. Watanabe, National Institute of Health and Nutrition, Tokyo; M. Akabane, Tokyo University of Agriculture, Tokyo; T. Kadowaki, Tokyo University, Tokyo; M. Noda and T. Mizoue, International Medical Center of Japan, Tokyo; Y. Kawaguchi, Tokyo Medical and Dental University, Tokyo; Y. Takashima, Kyorin University, Tokyo; K. Nakamura, Niigata University, Niigata; S. Matsushima and S. Natsukawa, Saku General Hospital, Nagano; H. Shimizu, Sakihae Institute, Gifu; H. Sugimura, Hamamatsu University, Shizuoka; S. Tominaga, Aichi Cancer Center Research Institute, Aichi; H. Iso, Osaka University, Osaka; M. Iida, W. Ajiki, and A. Ioka, Osaka Medical Center for Cancer and Cardiovascular Disease, Osaka; S. Sato, Osaka Medical Center for Health Science and Promotion, Osaka; E. Maruyama, Kobe University, Hyogo; M. Konishi, K. Okada, and I. Saito, Ehime University, Ehime; N. Yasuda, Kochi University, Kochi; S. Kono, Kyushu University, Fukuoka.

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Inoue, M., Kurahashi, N., Iwasaki, M. et al. 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).Cancer Causes Control 20, 741–750 (2009). https://doi.org/10.1007/s10552-008-9287-6

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