Reply to the letter to the editor on hepatitis B virus infection adds lymphoma burden in Korea

Abstract

We appreciate the valuable comments of Dr Huh on our article about the population attributable fraction (PAF) of infectious agents on cancer in Korea [1.Huh J. Suh C. Hepatitis B virus infection adds lymphoma burden in Korea.Ann Oncol. 2012; 23: 1926Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar]. As Dr Huh mentioned in her letter, evidence on the etiological link between hepatitis B virus (HBV) infection and non-Hodgkin's lymphoma (NHL) has emerged in several epidemiological studies. A meta-analysis of case–control studies suggested an odds ratio of 2.67 for detecting HBV infection in NHL cases when compared with the control population [2.Nath A. Agarwal R. Malhotra P. Varma S. Prevalence of hepatitis B virus infection in non-Hodgkin lymphoma: a systematic review and meta-analysis.Intern Med J. 2010; 40: 633-641Crossref PubMed Scopus (80) Google Scholar]. In addition, four cohort studies, including one study conducted among Korean population, have been published since 2007 and three of the reports were out after 2010 when our article was published [3.Engels E.A. Cho E.R. Jee S.H. Hepatitis B virus infection and risk of non-Hodgkin lymphoma in South Korea: a cohort study.Lancet Oncol. 2010; 11: 827-834Abstract Full Text Full Text PDF PubMed Scopus (166) Google Scholar, 4.Franceschi S. Lise M. Trepo C. et al.Infection with hepatitis B and C viruses and risk of lymphoid malignancies in the European Prospective Investigation into Cancer and Nutrition (EPIC).Cancer Epidemiol Biomarkers Prev. 2011; 20: 208-214Crossref PubMed Scopus (62) Google Scholar, 5.Fwu C.W. Chien Y.C. You S.L. et al.Hepatitis B virus infection and risk of intrahepatic cholangiocarcinoma and non-Hodgkin lymphoma: a cohort study of parous women in Taiwan.Hepatology. 2011; 53: 1217-1225Crossref PubMed Scopus (69) Google Scholar, 6.Ulcickas Yood M. Quesenberry Jr, C.P. Guo D. et al.Incidence of non-Hodgkin's lymphoma among individuals with chronic hepatitis B virus infection.Hepatology. 2007; 46: 107-112Crossref PubMed Scopus (115) Google Scholar]. Therefore, the roles of HBV in hematologic malignancy development, especially for NHL, need to be re-evaluated with more current results from these cohort studies. We conducted a meta-analysis of the four cohort studies on the HBV infection and NHL lymphoma, and found that the pooled relative risk was 1.96 [95% confidence interval (CI) 1.69–2.28] (Figure 1). The corresponding PAF for NHL was 8.02% (95% CI 5.9–10.4) for men and 6.38% (95% CI 4.7–8.3) for women in the application of the same method in our studies with the prevalence of HBV in the year 1990 [7.Shin A. Park S. Shin H.R. et al.Population attributable fraction of infection-related cancers in Korea.Ann Oncol. 2011; 22: 1435-1442Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar]. We, therefore, estimated that 222 NHL cases and 93 deaths among 3031 new cases and 1255 deaths from NHL in the year 2007 were attributed by HBV infection. Unlike hepatocellular carcinoma, whose incidence has decreased concordantly with decrease in the prevalence of hepatitis virus in Korean population, the age-standardized incidence rates for NHL have increased gradually between 1999 (4.5/100 000) and 2009 (6.0/100 000) with an annual percent change of 3.4% [8.Jung K.W. Park S. Kong H.J. et al.Cancer statistics in Korea: incidence, mortality, survival and prevalence in 2009.Cancer Res Treat. 2012; 44: 11-24Crossref PubMed Scopus (227) Google Scholar]. There is some evidence that HBV infection is more strongly associated with specific subtypes of NHL, for example diffuse large B-cell lymphoma [3.Engels E.A. Cho E.R. Jee S.H. Hepatitis B virus infection and risk of non-Hodgkin lymphoma in South Korea: a cohort study.Lancet Oncol. 2010; 11: 827-834Abstract Full Text Full Text PDF PubMed Scopus (166) Google Scholar, 5.Fwu C.W. Chien Y.C. You S.L. et al.Hepatitis B virus infection and risk of intrahepatic cholangiocarcinoma and non-Hodgkin lymphoma: a cohort study of parous women in Taiwan.Hepatology. 2011; 53: 1217-1225Crossref PubMed Scopus (69) Google Scholar] or malignant immunoproliferation [3.Engels E.A. Cho E.R. Jee S.H. Hepatitis B virus infection and risk of non-Hodgkin lymphoma in South Korea: a cohort study.Lancet Oncol. 2010; 11: 827-834Abstract Full Text Full Text PDF PubMed Scopus (166) Google Scholar], whereas follicular or T-cell NHL is not associated with HBV infection.The suggested putative mechanism for HBV infection causing NHL is the chronic activation of B cells in HBV-related hepatitis, which leads to DNA damage and transformation into lymphoma [3.Engels E.A. Cho E.R. Jee S.H. Hepatitis B virus infection and risk of non-Hodgkin lymphoma in South Korea: a cohort study.Lancet Oncol. 2010; 11: 827-834Abstract Full Text Full Text PDF PubMed Scopus (166) Google Scholar]. Still limited knowledge has been accumulated on the causes of NHL and role of HBV vaccination in the prevention of the development of NHL in Korea where a substantial decrease in the prevalence of surface antigen of hepatitis B virus was observed. However, we concluded that HBV infection attributed to the development of NHL cases (7.3%) and deaths (7.4%) without considering the joint effect of co-infection of HBV and HCV in Korea. By considering the effect of HBV infection in the development of NHL risk, the PAF of infectious agents for cancer from our previous report changed slightly from 21.2% to 21.3% for cancer incidence and from 24.7% to 24.8% for cancer death. These are very minor changes in the overall infection-related cancer incidences and deaths in Korea. In addition, we need further research on the increasing tendency of NHL incidence in spite of reduction in the prevalence of HBV since the introduction of HBV vaccination in Korea. The authors declare no conflicts of interest.