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Hepatoma Res. 2018;4. pii: 4. doi: 10.20517/2394-5079.2017.50. Epub 2018 Jan 26.
Qidong hepatitis B virus infection cohort: a 25-year prospective study in high risk area of primary liver cancer.Chen T1, Qian G2, Fan C1,2, Sun Y1, Wang J1, Lu P1, Xue X1, Wu Y1, Zhang Q1, Jin Y2, Wu Y2, Gan Y2, Lu J1, Kensler TW3, Groopman JD3, Tu H2.
Author information
1Department of Etiology, Qidong Liver Cancer Institute, Qidong People's Hospital, Qidong, 226200, Jiangsu, China.2State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200032, China.3Environmental Health and Engineering, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA.
AbstractQidong hepatitis B virus (HBV) infection cohort (QBC) is a prospective community-based study designed to investigate causative factors of primary liver cancer (PLC) in Qidong, China, where both PLC and HBV infection are highly endemic. Residents aged 20-65 years, living in seven townships of Qidong, were surveyed using hepatitis B surface antigen (HBsAg) serum test and invited to participate in QBC from June 1991 to December 1991. A total of 852 and 786 participants were enrolled in HBsAg-positive and HBsAg-negative sub-cohorts in May 1992, respectively. All participants were actively followed up in person, received HBsAg, alanine aminotransferase (ALT), alpha-fetoprotein (AFP) tests and upper abdominal ultrasonic examination, and donated blood and urine samples once or twice a year. The total response rate was 99.6%, and the number of incident PLC was 201 till the end of February 2017. The ratio of incidence rates was 12.32 (95% confidence interval[CI]=7.16-21.21, P < 0.0001) in HBsAg-positive arm compared with HBsAg-negative arm. The relative risk of PLC was 13.25 (95% CI=6.67-26.33, P < 0.0001) and 28.05 (95% CI=13.87-56.73, P < 0.0001) in the HBsAg+/HBeAg- group and the HBsAg+/HBeAg+ group, respectively, as compared to the HBsAg-/HBeAg- group. A series of novel PLC-related mutations including A2159G, A2189C and G2203W at the C gene, A799G, A987G and T1055A at the P gene of HBV genome were identified by using samples from the cohort. The mutation in hepatitis B virus (HBV) basal core promoter region of HBV genome has an accumulative effect on the occurrence of PLC. In addition, the tripartite relationship of aflatoxin exposure, P53 mutation and PLC was also investigated. Dynamic prediction model for PLC risk by using its long-term follow-up information and serial blood samples for QBC was developed. This model is expected to improve the efficiency of PLC screening in HBV infection individuals.
KEYWORDS: Prospective cohort; hepatitis B virus; primary liver cancer
PMID:29479565PMCID:PMC5824723DOI:10.20517/2394-5079.2017.50
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