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1 Epidemiology and Biostatistics Unit, Aviano Cancer Center, Aviano, Italy and 2 International Agency for Research on Cancer, Lyon, France
Requests for reprints: Luigino Dal Maso, Epidemiology and Biostatistics Unit, Centro di Riferimento Oncologico, IRCCS, Via Pedemontana occidentale 12, 33081 Aviano (PN), Italy. Phone: 39-0434-659354; Fax: 39-0434-659222. E-mail: epidemiology{at}cro.it
The present meta-analysis was conducted to evaluate the strength and the consistency of the association between hepatitis C virus (HCV) infection and non–Hodgkin lymphoma (NHL) and other lymphoid neoplasms. Only studies with 
100 cases which were also adjusted for sex and age were included. Fifteen case-control studies and three prospective studies contributed to present analysis, nine of which had not been included in previous meta-analyses. We calculated the pooled relative risks (RR) with corresponding 95% confidence intervals (95% CI), as a weighted average of the estimated RRs by random-effect models. The pooled RR of all NHL among HCV-positive individuals was 2.5 (95% CI, 2.1-3.0), but substantial heterogeneity was found between studies and by study design. Pooled RRs were 2.5 (95% CI, 2.1-3.1) in case-control studies and 2.0 (95% CI, 1.8-2.2) in cohort ones. The strongest source of heterogeneity seemed to be the prevalence of HCV among NHL-free study subjects (RR for NHL among HCV-positive individuals 3.0 and 1.9, respectively, for 5% and <5% HCV prevalence). RRs were consistently increased for all major B-NHL subtypes, T-NHL, and primary sites of NHL presentation. Thus, previous suggestions that the RRs for HCV differed by NHL subtype were not confirmed in our meta-analysis. Associations weaker than with NHL were found between HCV infection and Hodgkin's lymphoma (RR, 1.5; 95% CI, 1.0-2.1) and multiple myeloma (RR, 1.6; 95% CI, 0.7-3.6), but they were based on much fewer studies than NHL. The etiologic fraction of NHL attributable to HCV varies greatly by country, and may be upward of 10% in areas where HCV prevalence is high. (Cancer Epidemiol Biomarkers Prev 2006;15(11):2078–85)
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