Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
Lancet Oncol. 2010 Sep;11(9):827-34. doi: 10.1016/S1470-2045(10)70167-4. Epub 2010 Aug 3.
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.
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.
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.
During extended follow-up, HBsAg-positive individuals had an increased risk of NHL, suggesting that chronic HBV infection promotes lymphomagenesis.
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.
乙型肝炎病毒（HBV）感染在亚洲和非洲很常见。慢性 HBV 感染是否会增加非霍奇金淋巴瘤（NHL）的风险尚不清楚。我们旨在评估韩国队列中慢性 HBV 感染与随后 NHL 发展之间的关联。
韩国癌症预防研究是一项对韩国工人及其家属进行的队列研究，于 1992-95 年进行。从该队列中，我们排除了在 1993 年 1 月 1 日前死亡、在初始就诊时患有癌症、体重、身高、丙氨酸转氨酶或天冬氨酸转氨酶浓度、饮酒或有 HIV 或 HCV 感染证据的个体。在 1284586 名合格参与者中，有 603585 名参与者有基线血清乙型肝炎表面抗原（HBsAg）状态数据，纳入本研究。我们将基线时 HBsAg 阳性视为慢性 HBV 感染的证据。参与者从基线开始随访至 2006 年 12 月 31 日。我们使用住院和门诊诊断以及死亡率记录的国家数据库来确定血液系统恶性肿瘤的发生情况。我们评估了 NHL 总体以及 NHL 亚型、恶性免疫增殖、霍奇金淋巴瘤、多发性骨髓瘤和各种白血病的发病情况。我们使用 Cox 回归来评估 HBsAg 状态与 NHL 发病风险之间的关联，调整了性别、年龄和登记年份。
在 603585 名参与者中，有 53045 名（9%）在基线时 HBsAg 阳性。随后，有 133 名 HBsAg 阳性和 905 名 HBsAg 阴性的个体发展为 NHL。与 HBsAg 阴性的参与者相比，HBsAg 阳性的参与者 NHL 发病风险更高（总发病率为 19.4 比 12.3/100000 人年；调整后的 HR 为 1.74，95%CI 为 1.45-2.09）。在 NHL 亚型中，HBsAg 阳性与弥漫性大 B 细胞淋巴瘤（n=325，发病率为 6.86 比 3.79/100000 人年；调整后的 HR 为 2.01，1.48-2.75）和其他或未知亚型（n=591，发病率为 10.5 比 7.07/100000 人年；调整后的 HR 为 1.65，1.29-2.11）的发病风险增加相关，与 HBsAg 阴性相比。恶性免疫增殖（n=14，发病率为 0.44 比 0.15/100000 人年；调整后的 HR 为 3.79，1.05-13.7）也记录到风险增加。在 14 年的随访期间，HBsAg 阳性参与者的这些恶性肿瘤发病风险一直较高。HBsAg 阳性与滤泡性或 T 细胞 NHL、霍奇金淋巴瘤、多发性骨髓瘤或各种白血病无关。
在长期随访中，HBsAg 阳性个体的 NHL 发病风险增加，表明慢性 HBV 感染促进了淋巴瘤的发生。
韩国首尔市研究和国家癌症控制与发展计划，韩国保健福利部；美国国立癌症研究所。
