The Lancet Oncology, Volume 11, Issue 9, Pages 827 - 834, September 2010
doi:10.1016/S1470-2045(10)70167-4 Cite or Link Using DOI
Published Online: 04 August 2010
Original Text
Eric A Engels MD a, Eo Rin Cho PhD b, Prof Sun Ha Jee PhD c
Summary
Background
Hepatitis B virus (HBV) infection is common throughout Asia and Africa. Whether chronic HBV infection increases risk of non-Hodgkin lymphoma (NHL) is unclear. We aimed to assess the association between chronic HBV infection and subsequent development of NHL in a South Korean cohort.
Methods
The Korean Cancer Prevention Study is a cohort study of South Korean workers and their dependants enrolled during 1992—95. From this cohort, we excluded individuals who died before Jan 1, 1993, who had cancer at or before the initial visit, who had missing information about weight, height, alanine aminotransferase or aspartate aminotransferase concentrations, or alcohol use, or who had evidence of HIV or HCV infection. Of 1 284 586 eligible participants, 603 585 had baseline data for serum hepatitis B surface antigen (HBsAg) status and were included in our study. We regarded HBsAg positivity at baseline as evidence of chronic HBV infection. Participants were followed up from baseline until Dec 31, 2006. We used national databases of inpatient and outpatient diagnoses and mortality records to ascertain occurrence of haematological malignancies. We assessed incidence of NHL overall and of NHL subtypes, malignant immunoproliferation, Hodgkin's lymphoma, multiple myeloma, and various leukaemias. We used Cox regression to evaluate associations with HBsAg status, adjusting for sex, age, and enrolment year.
Findings
53 045 (9%) of 603 585 participants tested positive for HBsAg at baseline. Subsequently, 133 HBsAg-positive and 905 HBsAg-negative individuals developed NHL. HBsAg-positive participants had an increased risk of NHL overall compared with those who were HBsAg-negative (incidence 19·4 vs 12·3 per 100 000 person-years; hazard ratio [HR] 1·74, 95% CI 1·45—2·09, adjusted for sex, age at baseline, and enrolment year). Among NHL subtypes, HBsAg positivity was associated with increased risk of diffuse large B-cell lymphoma (n=325, incidence 6·86 vs 3·79 per 100 000 person-years; adjusted HR 2·01, 1·48—2·75) and other or unknown subtypes (n=591, incidence 10·5 vs 7·07 per 100 000 person-years; adjusted HR 1·65, 1·29—2·11), compared with HBsAg negativity. Increased risk was also recorded for malignant immunoproliferation (n=14, incidence 0·44 vs 0·15 per 100 000 person-years; adjusted HR 3·79, 1·05—13·7). Risk of these malignancies was consistently raised in HBsAg-positive participants throughout 14 years of follow-up. HBsAg positivity was not associated with follicular or T-cell NHL, Hodgkin's lymphoma, multiple myeloma, or various leukaemias.
Interpretation
During extended follow-up, HBsAg-positive individuals had an increased risk of NHL, suggesting that chronic HBV infection promotes lymphomagenesis.
Funding
Korean Seoul City Research and the National Research and Development Program for Cancer Control, Ministry for Health, Welfare and Family Affairs, Republic of Korea; US National Cancer Institute.
a Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA
b Institute of Human Genomic Study, College of Medicine, Korea University, Seoul, South Korea
c Department of Epidemiology, Institute for Health Promotion, Graduate School of Public Health, Seoul, South Korea
Correspondence to: Prof Sun Ha Jee, Department of Epidemiology and Health Promotion, Graduate School of Public Health, Yonsei University, Seoul, South Korea
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