1 Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, China.
2 Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China.
3 Pathology Center and Department of Pathology, Soochow University, Suzhou, China.
4 Qidong Liver Cancer Institute, The First People's Hospital of Qidong, Qidong, China.
5 Zhejiang Cancer Center, Zhejiang Cancer Hospital, Hangzhou, China.
6 Chinese Academy of Medical Sciences, Beijing, China.
7 Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, United Kingdom.
8 Department of Hepatobiliary Surgery, Nantong Tumor Hospital, Nantong, China.
9 Jiangsu Province Center for Disease Prevention and Control, Nanjing, China.
Hepatitis B virus (HBV) has been identified as a major risk factor for hepatocellular carcinoma. However, the associations between HBV infection and other cancer types are not well understood.
To assess the associations between chronic HBV infection and risk of all cancer types.
DESIGN, SETTING, AND PARTICIPANTS:
This population-based study involved 3 cohorts in China. The China Kadoorie Biobank (CKB) prospective cohort study, conducted between June 2004 and July 2008, used a dipstick assay for detection of serum hepatitis B surface antigen (HBsAg) among 496?732 participants to determine the association between HBV infection and risk of all cancer types. Two cohort studies were used to validate the associations by applying more precise serum HBsAg detection assays: the Qidong cohort (37?336 participants enrolled from November 2007 to April 2011) and the Changzhou nested case-control study (17?723 participants enrolled from June 2004 to September 2005). A total of 97 samples of stomach cancer tissues, 10 samples of pancreatic cancer tissues, and 9 samples of lung cancer tissues were included to assess the presence of HBV replication and expression. Statistical analysis was performed from December 2016 to October 2018.
Serum HBsAg status in the population-based stage and HBV DNA status, the expression of hepatitis B X protein, and hepatitis B core antibody (anti-HBc) in the tissue-based stage.
MAIN OUTCOMES AND MEASURES:
Incidence of all cancer types during follow-up.
In the CKB cohort, the mean (SD) age of the 496?732 participants was 51.5 (10.7) years; 59.0% of the participants were women. After 4.4 million person-years of follow-up, participants who were HBsAg seropositive (n = 15?355) had a higher risk of hepatocellular carcinoma (hazard ratio [HR], 15.77; 95% CI, 14.15-17.57), stomach cancer (HR, 1.41; 95% CI, 1.11-1.80), colorectal cancer (HR, 1.42; 95% CI, 1.12-1.81), oral cancer (HR, 1.58; 95% CI, 1.01-2.49), pancreatic cancer (HR, 1.65; 95% CI, 1.03-2.65), and lymphoma (HR, 2.10; 95% CI, 1.34-3.31) when compared with participants who were HBsAg seronegative (n = 481?377). Because of the limitation of sample size, only associations of HBV infection with hepatocellular carcinoma and stomach cancer were validated in the Qidong cohort (hepatocellular carcinoma: HR, 17.51; 95% CI, 13.86-22.11; stomach cancer: HR, 2.02; 95% CI, 1.24-3.29); the Changzhou nested case-control study validated only an association between HBV infection and stomach cancer (odds ratio, 1.76; 95% CI, 1.04-2.98). Moreover, among 22 participants with stomach cancer from the Qidong cohort who were anti-HBc seropositive, 12 samples (54.5%) of cancer tissues were HBV DNA positive, while among 25 participants with stomach cancer who were anti-HBc seronegative, no HBV DNA was detected. The same negative and positive rate was observed in the validation set from Zhejiang Tumor Hospital (19 of 35 samples [54.3%] were HBV DNA positive). Moreover, among the 8 patients with stomach cancer from the Qidong cohort who were anti-HBc seropositive, anti-HBc and hepatitis B X protein were expressed in all of their stomach cancer tissue samples. The same phenomenon was observed in the patients with pancreatic cancer but not in the patients with lung cancer, which was consistent with the population-based results of the CKB cohort.
CONCLUSIONS AND RELEVANCE:
This study found that HBV infection was also associated with the risk of nonliver cancer, especially digestive system cancers among adults in China.