Grant Number:	2R01CA085888-06A1 Interpret this number
Primary Investigator:	Loffredo, Christopher
Organization:	Georgetown University
Project Title:	Malignant Complications of Chronic Hcv
Fiscal Year:	2005

DESCRIPTION (provided by applicant): Five years ago we began these case-control studies (1R01CA85888) to assess the associations of environmental factors and of chronic infection with hepatitis C virus (HCV) with the risks of hepatocellular carcinoma (HCC) and non-Hodgkin's lymphoma (NHL) in Egypt. We selected Egypt as the study site because of the extremely high prevalence of HCV in that country, the increasing incidence of HCC and NHL, and uncertainty about the roles and attributable risks of HCV and environmental factors in the occurrence of these malignancies. Over 300 HCC cases, 300 NHL cases, and 475 non-cancer controls were recruited. Our results clearly demonstrate statistically significant associations of HCV with NHL and HCC. Exposure to agricultural pesticides was associated with HCC but not with NHL. In addition, we found that the genetic diversity of HCV in Egypt was much higher than previously known, and that the more genetically divergent strains were over-represented in HCC cases compared to controls. The continuing epidemic of HCV in Egypt, the significant association of pesticides with the risk of HCC, and the lack of competing risk factors (e.g. little chronic HBV, moderate to low aflatoxin exposure, and lack of alcohol consumption due to religious practices) represent a unique research setting that cannot be duplicated in other populations. In this competing renewal application we are proposing specific aims that flow logically from the original study results. During the next 5-year period we propose to continue recruiting new cases of HCC and NHL (N=300 in each group) and non-cancer controls (N=300 matched to HCC, and another 300 matched to NHL), so that the total sample size will be 600 HCC, 600 NHL, and 600 controls for each cancer, all with stored biological specimens and questionnaire data. Aim 1 is to assess gene-environment interactions in the etiology of HCC, specifically the role of polymorphisms in key antioxidant genes that mediate the toxicity of organophosphate pesticides. Aim 2 is to sequence the HCV genome from 200 matched pairs of HCC cases and controls, to determine the relative carcinogenicity of the genetic variants of HCV. Aim 3 is to examine associations with HCV and environmental factors with NHL, within molecular-defined subtypes of this heterogeneous malignancy. This set of aims and molecular epidemiology methods represents a novel approach to the study of the malignant complications of chronic HCV infection.




Viral transmission risk factors in an Egyptian population with high hepatitis C prevalence.
Authors: Mohlman M.K. , Saleh D.A. , Ezzat S. , Abdel-Hamid M. , Korba B. , Shetty K. , Amr S. , Loffredo C.A. .
Source: Bmc Public Health, 2015-10-07 00:00:00.0; 15, p. 1030.
EPub date: 2015-10-07 00:00:00.0.
PMID: 26446713
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Preventing hepatocellular carcinoma in Egypt: results of a Pilot Health Education Intervention Study.
Authors: Saleh D.A. , Amr S. , Jillson I.A. , Wang J.H. , Crowell N. , Loffredo C.A. .
Source: Bmc Research Notes, 2015-08-29 00:00:00.0; 8, p. 384.
EPub date: 2015-08-29 00:00:00.0.
PMID: 26319021
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Multiple pregnancies, hepatitis C, and risk for hepatocellular carcinoma in Egyptian women.
Authors: Amr S. , Iarocci E.A. , Nasr G.R. , Saleh D. , Blancato J. , Shetty K. , Loffredo C.A. .
Source: Bmc Cancer, 2014-11-29 00:00:00.0; 14, p. 893.
EPub date: 2014-11-29 00:00:00.0.
PMID: 25432765
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Knowledge and perceptions of hepatitis C infection and pesticides use in two rural villages in Egypt.
Authors: Saleh D.A. , Amr S. , Jillson I.A. , Wang J.H. , Khairy W.A. , Loffredo C.A. .
Source: Bmc Public Health, 2014-05-24 00:00:00.0; 14, p. 501.
EPub date: 2014-05-24 00:00:00.0.
PMID: 24886607
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Evaluation of midkine as a diagnostic serum biomarker in hepatocellular carcinoma.
Authors: Zhu W.W. , Guo J.J. , Guo L. , Jia H.L. , Zhu M. , Zhang J.B. , Loffredo C.A. , Forgues M. , Huang H. , Xing X.J. , et al. .
Source: Clinical Cancer Research : An Official Journal Of The American Association For Cancer Research, 2013-07-15 00:00:00.0; 19(14), p. 3944-54.
EPub date: 2013-07-15 00:00:00.0.
PMID: 23719264
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Immunohistochemical detection of hepatitis C virus (genotype 4) in B-cell NHL in an Egyptian population: correlation with serum HCV-RNA.
Authors: Gouda I. , Nada O. , Ezzat S. , Eldaly M. , Loffredo C. , Taylor C. , Abdel-Hamid M. .
Source: Applied Immunohistochemistry & Molecular Morphology : Aimm / Official Publication Of The Society For Applied Immunohistochemistry, 2010 Jan; 18(1), p. 29-34.
PMID: 19644357
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Viral and non-viral risk factors for non-Hodgkin's lymphoma in Egypt: heterogeneity by histological and immunological subtypes.
Authors: Goldman L. , Ezzat S. , Mokhtar N. , Abdel-Hamid A. , Fowler N. , Gouda I. , Eissa S.A. , Abdel-Hamid M. , Loffredo C.A. .
Source: Cancer Causes & Control : Ccc, 2009 Aug; 20(6), p. 981-7.
PMID: 19263231
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Detection of hepatocellular carcinoma using glycomic analysis.
Authors: Goldman R. , Ressom H.W. , Varghese R.S. , Goldman L. , Bascug G. , Loffredo C.A. , Abdel-Hamid M. , Gouda I. , Ezzat S. , Kyselova Z. , et al. .
Source: Clinical Cancer Research : An Official Journal Of The American Association For Cancer Research, 2009-03-01 00:00:00.0; 15(5), p. 1808-13.
EPub date: 2009-03-01 00:00:00.0.
PMID: 19223512
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Pilot survey of aflatoxin-albumin adducts in sera from Egypt.
Authors: Turner P.C. , Loffredo C. , Kafrawy S.E. , Ezzat S. , Eissa S.A. , Daly M.E. , Nada O. , Abdel-Hamid M. .
Source: Food Additives & Contaminants. Part A, Chemistry, Analysis, Control, Exposure & Risk Assessment, 2008 May; 25(5), p. 583-7.
PMID: 18473213
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Candidate markers for the detection of hepatocellular carcinoma in low-molecular weight fraction of serum.
Authors: Goldman R. , Ressom H.W. , Abdel-Hamid M. , Goldman L. , Wang A. , Varghese R.S. , An Y. , Loffredo C.A. , Drake S.K. , Eissa S.A. , et al. .
Source: Carcinogenesis, 2007 Oct; 28(10), p. 2149-53.
PMID: 17724376
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Genetic diversity in hepatitis C virus in Egypt and possible association with hepatocellular carcinoma.
Authors: Abdel-Hamid M. , El-Daly M. , Molnegren V. , El-Kafrawy S. , Abdel-Latif S. , Esmat G. , Strickland G.T. , Loffredo C. , Albert J. , Widell A. .
Source: The Journal Of General Virology, 2007 May; 88(Pt 5), p. 1526-31.
PMID: 17412982
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Peak selection from MALDI-TOF mass spectra using ant colony optimization.
Authors: Ressom H.W. , Varghese R.S. , Drake S.K. , Hortin G.L. , Abdel-Hamid M. , Loffredo C.A. , Goldman R. .
Source: Bioinformatics (oxford, England), 2007-03-01 00:00:00.0; 23(5), p. 619-26.
EPub date: 2007-03-01 00:00:00.0.
PMID: 17237065
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Liver disease in Egypt: hepatitis C superseded schistosomiasis as a result of iatrogenic and biological factors.
Authors: Strickland G.T. .
Source: Hepatology (baltimore, Md.), 2006 May; 43(5), p. 915-22.
PMID: 16628669
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Associations of pesticides, HCV, HBV, and hepatocellular carcinoma in Egypt.
Authors: Ezzat S. , Abdel-Hamid M. , Eissa S.A. , Mokhtar N. , Labib N.A. , El-Ghorory L. , Mikhail N.N. , Abdel-Hamid A. , Hifnawy T. , Strickland G.T. , et al. .
Source: International Journal Of Hygiene And Environmental Health, 2005; 208(5), p. 329-39.
PMID: 16217918
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Case-control study of non-Hodgkin's lymphoma and hepatitis C virus infection in Egypt.
Authors: Cowgill K.D. , Loffredo C.A. , Eissa S.A. , Mokhtar N. , Abdel-Hamid M. , Fahmy A. , Strickland G.T. .
Source: International Journal Of Epidemiology, 2004 Oct; 33(5), p. 1034-9.
PMID: 15155696
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