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.
|Mohlman, Mary Kate; Saleh, Doa'a A; Ezzat, Sameera et al. (2015) Viral transmission risk factors in an Egyptian population with high hepatitis C prevalence. BMC Public Health 15:1030|
|Saleh, Doa'a A; Amr, Sania; Jillson, Irene A et al. (2015) Preventing hepatocellular carcinoma in Egypt: results of a Pilot Health Education Intervention Study. BMC Res Notes 8:384|
|Amr, Sania; Iarocci, Emily A; Nasr, Ghada R et al. (2014) Multiple pregnancies, hepatitis C, and risk for hepatocellular carcinoma in Egyptian women. BMC Cancer 14:893|
|Saleh, Doa'a A; Amr, Sania; Jillson, Irene A et al. (2014) Knowledge and perceptions of hepatitis C infection and pesticides use in two rural villages in Egypt. BMC Public Health 14:501|
|Zhu, Wen-Wei; Guo, Jia-Jian; Guo, Lei et al. (2013) Evaluation of midkine as a diagnostic serum biomarker in hepatocellular carcinoma. Clin Cancer Res 19:3944-54|
|Gouda, Iman; Nada, Ola; Ezzat, Sameera et al. (2010) Immunohistochemical detection of hepatitis C virus (genotype 4) in B-cell NHL in an Egyptian population: correlation with serum HCV-RNA. Appl Immunohistochem Mol Morphol 18:29-34|
|Goldman, Lenka; Ezzat, Sameera; Mokhtar, Nadia et al. (2009) Viral and non-viral risk factors for non-Hodgkin's lymphoma in Egypt: heterogeneity by histological and immunological subtypes. Cancer Causes Control 20:981-7|
|Goldman, Radoslav; Ressom, Habtom W; Varghese, Rency S et al. (2009) Detection of hepatocellular carcinoma using glycomic analysis. Clin Cancer Res 15:1808-13|
|Turner, Paul C; Loffredo, Christopher; Kafrawy, Sharif El et al. (2008) Pilot survey of aflatoxin-albumin adducts in sera from Egypt. Food Addit Contam Part A Chem Anal Control Expo Risk Assess 25:583-7|
|Ressom, H W; Varghese, R S; Drake, S K et al. (2007) Peak selection from MALDI-TOF mass spectra using ant colony optimization. Bioinformatics 23:619-26|
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