Infection with Hepatitis B and C Viruses and Risk of Lymphoid Malignancies in the European Prospective Investigation into Cancer and Nutrition (EPIC)

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BlankInfection with Hepatitis B and C Viruses and Risk of Lymphoid Malignancies

in the European Prospective Investigation into Cancer and Nutrition (EPIC)

1.. Silvia Franceschi1,

2.. Mauro Lise2,

3.. Christian Trépo3,

4.. Pascale Berthillon3,

5.. Shu-Chun Chuang4,

6.. andra Nieters5,

7.. Ruth C. 6,

8.. Roel Vermeulen7,

9.. Kim Overvad8,

10.. Anne Tjønneland9,

11.. Anja Olsen9,

12.. a M. Bergmann10,

13.. Heiner Boeing10,

14.. Rudolf Kaaks11,

15.. Nikolaus Becker11,

16.. Antonia Trichopoulou12,13,

17.. Pagona Lagiou12,

18.. Bamia12,

19.. Domenico Palli14,

20.. Sabina Sieri15,

21.. Salvatore Panico16,

22.. rio Tumino17,

23.. Carlotta Sacerdote18,

24.. Bas Bueno-de-Mesquita19,20,

25.. Petra H.M. Peeters7,21,

26.. Laudina Rodríguez22,

27.. Leila Luján Barroso23,

28.. Miren Dorronsoro24,25,

29.. María-José Sánchez25,26,

30.. Carmen Navarro25,27,

31.. Aurelio Barricarte25,28,

32.. Sara Regnér29,

33.. Signe Borgquist30,

34.. Beatrice Melin31,

35.. Göran Hallmans32,

36.. Kay-Tee Khaw33,

37.. Nick Wareham34,

38.. Sabina Rinaldi1,

39.. Pierre Hainaut1,

40.. Elio Riboli4 and

41.. Paolo Vineis4

+ Author Affiliations

1.. Authors' Affiliations:1International Agency for Research on Cancer, Lyon

France; 2Aviano Cancer Center, Aviano, Italy; 3Institut National de la Santé et

de la Recherche Médicale (INSERM), Lyon, France; 4Imperial College London,

London, United Kingdom; 5Centre of Chronic Immunodeficiency, Freiburg Medical

Centre and University of Freiburg, Freiburg, Germany; 6Cancer Epidemiology Unit,

University of Oxford, Oxford, United Kingdom; 7Julius Center for Health Sciences

and Primary Care, Department of Epidemiology, University of Utrecht, Utrecht,

the Netherlands; 8 Department of Epidemiology, School of Public Health, Aarhus

University, Aarhus, Denmark; 9Institute of Cancer Epidemiology, Danish Cancer

Society, Copenhagen, Denmark; 10German Institute of Human Nutrition,

Potsdam-Rehbrücke, Nuthetal, Germany; 11German Cancer Research Center (DKFZ),

Heidelberg, Germany; 12WHO Collaborating Center for Food and Nutrition Policies,

Department of Hygiene, Epidemiology and Medical Statistics, University of Athens

Medical School, Athens, Greece; 13Hellenic Health Foundation, Athens, Greece;

14Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention

Institute-ISPO, Florence, Italy; 15Nutritional Epidemiology Unit, Fondazione

IRCCS Istituto Nazionale dei Tumori, Milan, Italy; 16Department of Clinical and

Experimental Medicine Federico II University, Naples, Italy; 17Cancer Registry

and Histopathology Unit, District 1 Hospital, Ragusa, Italy; 18CPO-Piemonte,

Turin, Italy; 19National Institute for Public Health and Environment (RIVM),

Bilthoven, the Netherlands; 20Department of Gastroenterology and Hepatology,

University Medical Centre Utrecht (UMCU), Utrecht, the Netherlands; 21Department

of Epidemiology and Biostatistics, School of Public Health, Faculty of Medicine,

Imperial College London, London, United Kingdom; 22Public Health and

Participation Directorate, Health and Health Care Services Council, Asturias,

Spain; 23Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research

Programme, Catalan Institute of Oncology, Barcelona, Spain; 24Public Health

Division of Gipuzkoa, Basque Government, San Sebastian, Spain; 25CIBER

Epidemiología y Salud Pública (CIBERESP), Spain; 26Andalusian School of Public

Health, Granada, Spain; 27Department of Epidemiology, Regional Health Authority,

Murcia, Spain; 28Navarra Public Health Institute, Pamplona, Spain; 29Department

of Surgery, Skåne University Hospital Malmö, Lund University, Malmö, Sweden;

30Department of Oncology, Skåne University Hospital Lund, Lund University, Lund,

Sweden; 31Department of Radiation Sciences, Umeå University, Umeå, Sweden;

32Public Health and Clinical Medicine, University Hospital of Northern Sweden,

Umeå, Sweden; 33University of Cambridge, Cambridge, United Kingdom; and 34MRC

Epidemiology Unit, Institute of Metabolic Science, Cambridge, United Kingdom

1.. Corresponding Author:

Silvia Franceschi, International Agency for Research on Cancer, 150 cours

Albert , 69372 Lyon, cedex 08, France. Phone: 33-472738402; Fax:

33-472738345. E-mail: franceschi@...

Abstract

Background: Case–control studies suggested a moderate, but consistent,

association of hepatitis C virus (HCV) infection with lymphoid tissue

malignancies, especially non–Hodgkin lymphoma (NHL). More limited data suggested

that hepatitis B virus (HBV) infection might also be associated with NHL.

However, prospective studies on the topic are few.

Methods: A nested case–control study was conducted in eight countries

participating in the EPIC prospective study. Seven hundred thirty-nine incident

cases of NHL, 238 multiple myeloma (MM), and 46 Hodgkin lymphoma (HL) were

matched with 2,028 controls. Seropositivity to anti-HCV, anti-HBc, and HBsAg was

evaluated and conditional logistic regression was used to estimate odds ratios

(OR) and corresponding 95% confidence intervals (CI) for NHL, MM, or HL, and

their combination.

Results: Anti-HCV seropositivity among controls in different countries ranged

from 0% to 5.3%; HBsAg from 0% to 2.7%; and anti-HBc from 1.9% to 45.9%. Similar

nonsignificant associations were found with seropositivity to HBsAg for NHL (OR

= 1.78; 95% CI: 0.78–4.04), MM (OR = 4.00; 95% CI: 1.00–16.0), and HL (OR =

2.00; 95% CI: 0.13–32.0). The association between HBsAg and the combination of

NHL, MM, and HL (OR = 2.21; 95% CI: 1.12–4.33) was similar for cancer diagnosed

less than 3 and 3 or more years after blood collection. No significant

association was found between anti-HCV and NHL, MM, or HL risk, but the

corresponding CIs were very broad.

Conclusions: Chronic HBV infection may increase the risk of lymphoid

malignancies among healthy European volunteers.

Impact: Treatment directed at control of HBV infection should be evaluated in

HBsAg-seropositive patients with lymphoid tissue malignancies. Cancer Epidemiol

Biomarkers Prev; 20(1); 208–14. ©2011 AACR.