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Declining rates of hepatocellular carcinoma in urban Shanghai: incidence trends in 1976–2005

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In China, hepatocellular carcinoma (HCC) incidence rates in several registry catchment populations are amongst the highest worldwide. The incidence rates in urban Shanghai were analyzed between 1976 and 2005 to describe and interpret the time trends. Age-specific and age-standardized rates were calculated and graphically presented. An age-period-cohort model was fitted to assess the effects of age at diagnosis, calendar period, and birth cohort on the changing HCC incidence rates. In total, 35,241 and 13,931 men and women were diagnosed with HCC during 1976–2005 in urban Shanghai. The age-standardized incidence rates in urban Shanghai were 33.9 per 105 among men and 11.4 per 105 among women in 1976–1980, but decreased in both sexes to 25.8 per 105 and 8.5 per 105, respectively by 2001–2005. Accelerating rates in birth cohorts born in the early-1930s and decelerating rates circa 1945 were observed in both sexes, with further accelerations noted in the late-1950s (in women) and early-1960s (in men). Given the parameterization, increases in risk of HCC were seen in successive male and female generations between 1900 and 1935, followed by a further increase among successive cohorts born around 1960, with a reduction in risk in the most recent generations. The incidence rates of HCC in urban Shanghai from 1976 to 2005 have declined in both sexes, with the complex but similar patterns observed in successive generations suggestive of a shared changing prevalence in risk factors in men and women, with a role possibly for HBV interventions reducing risk of HCC in cohorts born after 1960.

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  1. International Agency for Research on Cancer. GLOBOCAN 2008: cancer incidence and mortality worldwide in 2008. 2008. Cited 2010 December 1. Available from:

  2. Curado MP, Edwards B, Shin HR, Storm H, Ferlay J, Heanue M, Boyle P. Cancer incidence in five continents, vol. IX. Lyon: IARC Scientific Publications; 2007. vol. 160, pp. 1–897.

  3. International Agency for Research on Cancer. Cancer incidence in five continents. 2010 [Internet] [cited 2010 December 3]. Available from URL:

  4. The Shanghai Cancer Registry. The incidence rates of malignant tumors in urban Shanghai, 2007. Tumor (Shanghai) 2010;30:726.

  5. Clayton D, Schifflers E. Models for temporal variation in cancer rates I: age-period and age-cohort models. Stat Med. 1987;6(4):449–67.

    Article  PubMed  CAS  Google Scholar 

  6. Clayton D, Schifflers E. Models for temporal variation in cancer rates II: age- period- cohort models. Stat Med. 1987;6(4):469–81.

    Article  PubMed  CAS  Google Scholar 

  7. Lee LT, Huang HY, Huang KC, Chen CY, Lee WC. Age-period-cohort analysis of hepatocellular carcinoma mortality in Taiwan, 1976–2005. Ann Epidemiol. 2009;19(5):323–8.

    Article  PubMed  Google Scholar 

  8. Dal Maso L, Lise M, Zambon P, Crocetti E, Serraino D, Ricceri F, Vercelli M, De Lisi V, Tagliabue G, Federico M, Falcini F, Cassetti T, et al. Incidence of primary liver cancer in Italy between 1988 and 2002: an age-period-cohort analysis. Eur J Cancer. 2008;44(2):285–92.

    Article  PubMed  Google Scholar 

  9. Gao YT, Lu W. Cancer incidence, mortality and survival rates in urban Shanghai (1973-2000). Shanghai: Second Military Medical University Press; 2007. p. 443.

  10. Carstensen B. Age-period cohort models for the Lexis diagram. Stat Med. 2007;26(15):3018–45.

    Article  PubMed  CAS  Google Scholar 

  11. Parkin DM, Whelan SL, Ferlay J, Teppo L, Thomas DB. Cancer incidence in five continents, vol. VIII. Lyon, France: IARC Science Publication; 2002. vol. 155, pp. 1–781.

  12. Hankey BF, Ries LA, Kosary CL, Feuer EJ, Merrill RM, Clegg LX, Edwards BK. Partitioning linear trends in age-adjusted rates. Cancer Cause Control. 2000;11(1):31–5.

    Article  CAS  Google Scholar 

  13. Viel JF, Fournier E, Danzon A. Age-period-cohort modeling of non-Hodgkin’s lymphoma incidence in a French region: a period effect compatible with an environmental exposure. Environ Health. 2010;9:47.

    Article  PubMed  Google Scholar 

  14. Zong ZH, Shen QJ, Chen JG, Li WG, Yao HY. Application of Bayesian graphical modeling to analysis of the incidence data of primary liver cancer in Qidong county. Chin J Health Stat. 2005;22:13–5.

    Google Scholar 

  15. Shen QJ, Zhang XF, Chen JG, Li WG, Yao HY. An age-period-cohort modeling study on primary liver cancer incidence rate in Qidong. Clin J Epidemiol. 2004;25:902–4.

    Google Scholar 

  16. R Development Core Team. R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. 2010. ISBN 3-900051-07-0. [Internet] 2010 [cited 2010 December 3]. Available from:

  17. Carstensen B, Plummer M, Laara E, Hills M, et. al. Epi: a package for statistical analysis in epidemiology. R package version 1.1.17. 2010. [Internet] [cited 2010 December 3]. Available from:

  18. Chuang SC, La Vecchia C, Boffetta P. Liver cancer: descriptive epidemiology and risk factors other than HBV and HCV infection. Cancer Lett. 2009;286(1):9–14.

    Google Scholar 

  19. Veldt BJ, Chen W, Heathcote EJ, Wedemeyer H, Reichen J, Hofmann WP, de Knegt RJ, Zeuzem S, Manns MP, Hansen BE, Schalm SW, Janssen HL. Increased risk of hepatocellular carcinoma among patients with hepatitis C cirrhosis and diabetes. Hepatology. 2008;47(6):1856–62.

    Article  PubMed  Google Scholar 

  20. Lu F, Zhuan H. Prevention of hepatitis B in China: achievements and challenges. Chin Med J. 2009;122:2925–7.

    PubMed  Google Scholar 

  21. Barazani Y, Hiatt JR, Tong MJ, Busuttil RW. Chronic viral hepatitis and hepatocellular carcinoma. World J Surg. 2007;31(6):1243–8.

    Article  PubMed  Google Scholar 

  22. Yao GB. Importance of perinatal versus horizontal transmission of hepatitis B virus infection in China. Gut. 1996;38(Suppl 2):S39–42.

    Article  PubMed  Google Scholar 

  23. Li YT, Wu HY, Zhang AX, Shen WJ, Yuan GJ. Epidemiological effect observed after hepatitis B immunization of newborns in different regions in Shanghai. Shanghai J Prev Med. 2000;12:410–1.

    Google Scholar 

  24. Lu W, Zheng Y. Prevalence and prevention measure of cancer in Shanghai. China Cancer. 2009;18:90–1.

    Google Scholar 

  25. Zhang AX, Li YT, Xu Q, et al. Review and measures of hepatitis B immunization in Shanghai. Shanghai J Prev Med. 2000;12:408–10.

    Google Scholar 

  26. Castells L, Vargas V, Gonzalez A, Esteban J, Esteban R, Guardia J. Long interval between HCV infection and the development of hepatocellular carcinoma. Liver. 1995;15(3):159–63.

    PubMed  CAS  Google Scholar 

  27. Zhao SJ, Xu ZY, Lu Y. A mathematical model of hepatitis B virus transmission and its application for vaccination strategy in China. Int J Epidemiol. 2000;29(4):744–52.

    Article  PubMed  CAS  Google Scholar 

  28. Lu W, Li DL, Zheng Y. Conception of cancer prevention and control strategy in Shanghai. China Cancer. 2001;10:187–8.

    Google Scholar 

  29. Wang J, Liu XM. Assessment of dietary aflatoxins exposure in Chinese residents. Chin J Food Hygiene. 2007;19(3):238–40.

    Google Scholar 

  30. Yeh FS, Shen KN. Epidemiology and early diagnosis of primary liver cancer in China. Adv Cancer Res. 1986;47:297–329.

    Article  Google Scholar 

  31. China Cancer Prevention and Treatment Office. The diagnostic standard on primary liver cancer. Chin J Hepato Surg. 1998;4:103.

    Google Scholar 

  32. Keyes KM, Utz RL, Robinson W, Li GH. What is a cohort effect? Comparison of three statistical methods for modeling cohort effects in obesity prevalence in the United States, 1971–2006. Soc Sci Med. 2010;70(7):1100–8.

    Article  PubMed  Google Scholar 

  33. Reimers LL, Anderson WF, Rosenberg PS, Henson DE, Castle PE. Etiological heterogeneity for cervical carcinoma by histopathological type, using comparative age-period-cohort (APC) models. Cancer Epidemiol Biomarkers Prev. 2009;18(3):792–800.

    Article  PubMed  Google Scholar 

  34. Jia WH, Huang QH, Liao J, et al. Trends in incidence and mortality of nasopharyngeal carcinoma over a 20-25 year period (1978/1983–2002) in Sihui and Cangwu counties in southern China. BMC Cancer. 2006;6:178.

    Article  PubMed  Google Scholar 

  35. Gao S, Yang WS, Gao J, Wang J, Xiang YB. A Meta-analysis of cohort studies on the association between diabetes and the risk of primary liver cancer. Chin J Prev Med. 2010;44(8):711–6.

    Google Scholar 

  36. Lai MS, Hsieh MS, Chiu YH, Chen TH. Type 2 diabetes and hepatocellular carcinoma: a cohort study in high prevalence area of hepatitis virus infection. Hepatology. 2006;43(6):1295–302.

    Article  PubMed  Google Scholar 

  37. Kiyosawa K, Umemura T, Ichijo T, Matsumoto A, Yoshizawa K, Gad A, Tanaka E. Hepatocellular carcinoma: recent trends in Japan. Gastroenterology. 2004;127(5 Suppl 1):S17–26.

    Article  PubMed  Google Scholar 

  38. Samanic C, Chow WH, Gridley G, Jarvholm B, Fraumeni JF Jr. Relation of body mass index to cancer risk in 362, 552 Swedish men. Cancer Causes Control. 2006;17(7):901–9.

    Article  PubMed  Google Scholar 

  39. Ohishi W, Fujiwara S, Cologne JB, Suzuki G, Akahoshi M, Nishi N, Takahashi I, Chayama K. Risk factors for hepatocellular carcinoma in a Japanese population: a nested case-control study. Cancer Epidemiol Biomarkers Prev. 2008;17(4):846–54.

    Article  PubMed  CAS  Google Scholar 

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Dr. Puthiery Va, a training fellow from University of New England College of Osteopathic Medicine, was supported by the Fogarty International Clinical Research Scholars and Fellows Support Center at the Vanderbilt Institute for Global Health, funded by the Fogarty International Center, NIH, through an R24 Training Grant (Grant number: R24TW007988). This work was supported by the fund of the state key project specialized for infectious diseases of China (No. 2008ZX10002-015).

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Correspondence to Yong-Bing Xiang.

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Shan Gao and Wan-Shui Yang contributed equally to this work.

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Gao, S., Yang, WS., Bray, F. et al. Declining rates of hepatocellular carcinoma in urban Shanghai: incidence trends in 1976–2005. Eur J Epidemiol 27, 39–46 (2012).

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