We investigated Hepatitis C virus (HCV) seropositivity and the risk of non-Hodgkin lymphoma (NHL) in a population-based case-control study in British Columbia, Canada. Cases were aged 20-79, diagnosed between March 2000 and February 2004, and resident in greater Vancouver or Victoria. Cases with HIV or a prior transplant were excluded. Controls were chosen from the Client Registry of the British Columbia (BC) Ministry of Health, and were age/sex/region frequency matched to cases. Antibodies for HCV were measured in 795 cases and 697 control subjects. HCV seropositivity was 2.4% in cases and 0.7% in controls [odds ratio (OR) 5 2.6, 95% confidence interval (CI) 5 0.9-7.4]. A significantly elevated risk was observed for B-cell lymphoma (OR 5 2.9, 95%CI 5 1.0-8.6). The highest risks were associated with diffuse large B-cell lymphoma (OR 5 7.3, 95%CI 5 2.1-25.0) and marginal zone lymphoma (OR 5 6.1, 95%CI 5 1.1-33.9). Our results provide further evidence that HCV infection contributes to NHL risk. ' 2007 Wiley-Liss, Inc.Key words: non-Hodgkin lymphoma; virus; hepatitis; hepatitis C; epidemiology; etiology The incidence of non-Hodgkin lymphoma (NHL) has been rising steadily for the past 30 years, but has leveled off in recent years. 1,2 Hepatitis C virus (HCV) infection is well-known to be the primary risk factor for type II mixed cryoglobulinemia (MC). 3,4 MC is a nonmalignant lymphoproliferative condition, which may evolve into B-cell NHL in 5-8% of cases. 5 This possible association between HCV infection and NHL was first suggested in 1993. 6 The epidemiologic evidence concerning this potential association was recently reviewed. 7 Overall, there was a 2-fold risk of NHL associated with HCV, but there was significant heterogeneity found between studies based on study design and HCV prevalence. Higher risks were found with case-control studies particularly those using hospital controls and in studies in high HCV prevalence areas.HCV was first identified in 1989, and was known as ''NonA, NonB Hepatitis'' to describe inflammatory liver disease not attributable to infection with Hepatitis A or Hepatitis B. 8 The World Health Organization estimates there are 170 million people, around 3% of the world's population, infected with hepatitis C, with 3-4 million new infections per year. 9 In Canada, it is estimated that there are 250,000 people (0.8%) infected with hepatitis C and that as few as 30% of those who have hepatitis C know they are infected. 10 The prevalence of HCV infection in British Columbia (BC) is estimated to be 1.5%, nearly twice the national rate, likely due to a high rate of injection drug use (IDU). 11,12 To further investigate the association between HCV infection and NHL in a low prevalence area, we examined data from a population-based case-control study in BC, Canada.
Material and methods
Study populationThe methodology has been described previously. 13 Between March 2000 and February 2004, NHL cases from the Greater Vancouver Regional District (GVRD) and the Capital Regional District (CRD), which i...