Hepatitis C and risk of lymphoma: results of the European multicenter case-control study EPILYMPH.
OBJECTIVE
Increasing evidence points toward a role of hepatitis C virus (HCV) infection in the etiology of malignant lymphomas. However, previous epidemiologic studies were limited in size to establish an association between HCV infection and specific lymphoma subtypes. We performed a large, multicenter, case-control study to address this question.


METHODS
The study comprised 5 European countries and included newly diagnosed cases of any lymphoid malignancy recruited between 1998 and 2004. Controls were matched to cases by 5-year age group, sex, and study center. In-person interviews were conducted to collect data on demographic, medical, and family history as well as environmental exposures. Serum samples of 1807 cases and 1788 controls (excluding human immunodeficiency virus-positive and organ-transplantation subjects) were screened for HCV infection using an enzyme immunoassay. Positive as well as randomly selected negative samples were subjected to HCV RNA detection and HCV genotyping.


RESULTS
HCV infection was detected in 53 (2.9%) lymphoma cases and in 41 (2.3%) control subjects (odds ratio [OR], 1.42; 95% confidence interval [CI]: 0.93-2.15). Restricted to individuals who tested positive for HCV-RNA (indicating persistent infection and active viral replication), the OR was 1.82 (95% CI: 1.13-2.91). In subtype-specific analyses, HCV prevalence was associated with diffuse large B-cell lymphoma (OR, 2.19; 95% CI: 1.23-3.91) but not with chronic lymphocytic leukemia or follicular, Hodgkin's, or T-cell lymphoma. The sample size was not sufficient to derive any conclusions for rare lymphoma entities such as splenic marginal zone lymphoma.


CONCLUSIONS
These results support a model that chronic HCV replication contributes to lymphomagenesis and establish a specific role of HCV infection in the pathogenesis of diffuse large B-cell lymphoma.
Nieters
Alexandra
A
German Cancer Research Center, Heidelberg, Germany. a.nieters@dkfz.de
Kallinowski
Birgit
B
Brennan
Paul
P
Ott
Melanie
M
Maynadié
Marc
M
Benavente
Yolanda
Y
Foretova
Lenka
L
Cocco
Pier Luigi
PL
Staines
Anthony
A
Vornanen
Martine
M
Whitby
Denise
D
Boffetta
Paolo
P
Becker
Nikolaus
N
De Sanjosé
Silvia
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D003627:Data Interpretation, Statistical; D005060:Europe / Q000453:epidemiology; D005260:Female; D016174:Hepacivirus / Q000235:genetics / Q000472:pathogenicity; D006526:Hepatitis C / Q000097:blood / Q000150:complications* / Q000453:epidemiology*; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000097:blood / Q000453:epidemiology* / Q000821:virology*; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D012367:RNA, Viral / Q000097:blood; D012307:Risk Factors
D012367:RNA, Viral