Hepatitis C virus and other risk factors in hepatocellular carcinoma.

UNLABELLED: Hepatocellular carcinoma (HCC) increased in Egypt in the past years, becoming the most common cancer among men. Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the known primary risk factors for HCC. This study describes the viral profile of HCC in a predominantly rural area in Egypt. We included 148 HCC cases and 148 controls from the Tanta Cancer Center and the Gharbiah Cancer Society in the Nile delta region. Serological (ELISA) and molecular (PCR) analysis for HBV and HCV infection were performed on plasma samples from each subject. Epidemiologic, environmental, and medical histories were collected by interviewing of subjects. Around 90.5% of cases and controls were from rural areas. HCV infection was high in both cases and controls (89.2% and 49.3%, for cases and controls respectively by serology). HCV was the most important HCC risk factor [OR 9.7 (95% CI: 3.3-28.0, P <0.01)], and HBV infection showed marginal tendency of increased risk [OR 5.4 (95% CI: 0.9-31.8, P <0.06)]. Ever worked in farming [OR 2.8 (95% CI: 1.1-7.2, P <0.03)] and history of cirrhosis [OR 3.6 (95% CI: 1.6-8.1, P <0.01)] or blood transfusion [OR 4.2 (95% CI: 0.99-17.8, P <0.05)] were also associated with increased HCC risk. This study in a predominantly rural area in Egypt supports previous reports from other parts of Egypt that HCV infection is the primary HCC risk factor in Egypt. Further understanding of the relationship between infection and other risk factors in the development of HCC could lead to targeted interventions for at-risk individuals. KEYWORDS: hepatocellular carcinoma; hepatitis; rural; risk factors; Egypt.

Geographic distribution of hematopoietic cancers in the Nile delta of Egypt.

BACKGROUND: Previous evidence indicated that incidence rates of non-Hodgkin's lymphoma (NHL) are high in Egypt although little is known about risk factors. MATERIALS AND METHODS: Using data from the population-based cancer registry of Gharbiah governorate in Egypt, we assessed the 1999-2005 incidence of hematopoietic cancers (HCs) based on the ICD-O3 by age- and sex-specific urban-rural distribution. RESULTS: NHL showed the highest incidence among all HCs (11.7 per 100 000). Urban incidence of HCs was higher than rural incidence. Incidence rates of Hodgkin's lymphoma (HL) and NHL were high especially among urban males up to the 64-year age category. Rural incidence of HL and NHL was high below age 20. Among the districts of the governorate, we observed NHL incidence pattern similar to that observed for hepatocellular carcinoma because of the possible link to hepatitis C virus for both cancers. Comparison to the published HCs data from Algeria, Cyprus, and Jordan showed the highest NHL rate in Egypt than the other countries in the region. CONCLUSIONS: Future studies should define the role of environmental exposures in hematopoietic carcinogenesis in this population. In-depth studies should also investigate the role of access to health care in the urban-rural variation of HC distribution in this population.

Urban-rural differences of gynaecological malignancies in Egypt (1999-2002).

OBJECTIVE: In previous studies, we have shown a three to four times higher urban incidence of breast cancer and estrogen receptor-positive breast cancers in the Gharbiah Province of Egypt. We investigated the urban-rural incidence differences of gynaecologic malignancies (uterine, ovarian and cervical cancers) to explore if they show the same trend that we found for breast cancer. DESIGN: Cancer registry-based incidence comparison. SETTING: Gharbiah population-based cancer registry (GPCR), Tanta, Egypt. SAMPLE: All patients with uterine, ovarian and cervical cancer in GPCR from 1999 to 2002. METHODS: We calculated uterine, ovarian and cervical cancer incidence from 1999 to 2002. For each of the three cancers, we calculated the overall and age-specific rates for the province as a whole, and by urban-rural status, as well as for the eight districts of the province. RESULTS: Incidence of all three cancer sites was higher in urban than in rural areas. Uterine cancer showed the highest urban-rural incidence rate ratio (IRR = 6.07, 95% CI = 4.17, 8.85). Uterine cancer also showed the highest urban incidence in the oldest age group (70+ age category, IRR = 14.39, 95% CI = 4.24, 48.87) and in developed districts (Tanta, IRR = 4.14, 95% CI = 0.41, 42.04). Incidence rates by groups of cancer sites showed an increasing gradient of urban incidence for cancers related to hormonal aetiology, mainly of the breast and uterus (IRR = 4.96, 95% CI = 2.86, 8.61). CONCLUSIONS: The higher urban incidence of uterine cancer, coupled with our previous findings of higher incidence of breast cancer and estrogen receptor positive breast cancer in urban areas in this region, may be suggestive of possible higher exposure to environmental estrogenic compounds, such as xenoestrogens, in urban areas.

Contrasting molecular pathology of colorectal carcinoma in Egyptian and Western patients.

Colorectal carcinoma is uncommon in Egypt, but a high proportion of cases occurs before age 40 years and in the rectum. We compared the molecular pathology of 59 representative Egyptian patients aged 10-72 to Western patients with sporadic, young-onset, or hereditary non-polyposis colorectal cancer syndrome (HNPCC)-associated carcinoma and found significant differences. Most Egyptian cancers were rectal (51%) and poorly differentiated (58%). High levels of microsatellite instability (MSI-H) were frequent (37%) and attributable in some cases (36%) to methylation of the promoter of the hMLH1 mismatch repair gene, but no MSI-H cancer had loss of hMSH2 mismatch repair gene product of the type seen with germline hMSH2 mutation in HNPCC. K-ras mutation was uncommon (11%). In subset analyses, high frequencies of MSI-H in rectal carcinomas (36%) and p53 gene product overexpression in MSI-H cancers (50%) were found. MSI-H and K-ras mutation in Egyptians under age 40 were unusual (17% and 0%, respectively), and schistosomiasis was associated with MSI and K-ras mutation. Cluster analysis identified 2 groups: predominantly young men with poorly differentiated mucinous and signet-ring cell colorectal carcinoma lacking K-ras mutation; older patients who had well- or moderately differentiated adenocarcinoma often with MSI-H, K-ras mutation and schistosomiasis. Our findings show that the molecular pathology of colorectal cancer in older as well as younger Egyptians has unique differences from Western patients, and schistosomiasis influences the molecular pathogenesis of some tumours.

Inheritance of the 194Trp and the 399Gln variant alleles of the DNA repair gene XRCC1 are associated with increased risk of early-onset colorectal carcinoma in Egypt.

Patients under age 40 constitute 35.6% of all colorectal cancer cases in Egypt, an unusual disease pattern to which both environmental exposures and inefficient DNA repair may contribute. While a number of polymorphisms in DNA repair genes have been recently identified, their role as cancer risk modifiers is yet to be determined. In a pilot case-control study, we tested the hypothesis that polymorphisms in the gene for the DNA repair enzyme XRCC1 are associated with increased risk of colorectal cancer among Egyptians. Using a multiplex polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology, allelic variants of the XRCC1 gene at codons 194 (Arg-->Trp) (194Trp) and 399 (Arg-->Gln) (399Gln), were analyzed in DNA from lymphocytes of 48 newly-diagnosed colorectal cancer cases and 48 age- and sex-matched controls. Overall, the inheritance of 194Trp allele (Arg/Trp genotype) and 399Gln allele (combined Arg/Gln and Gln/Gln genotypes) was associated with increased colorectal cancer risk (odds ratio (OR)=2.56, 95% confidence limits (CL) 0.73-9.40, and P=0. 08 for 194Trp allele and OR=3.98, 95% CL 1.50-10.6, and P<0.001 for 399Gln allele). Interestingly, the frequencies of 194Trp and 399Gln genotypes were higher in colorectal cancer cases under age 40 than in corresponding controls, and an association between both polymorphisms and early age of disease onset was observed (OR=3.33, 95% CL 0.48-35.90, and P=0.16 for 194Trp and OR=11.90, 95% CL 2.30-51.50, and P=0.0003 for 399Gln). Analysis of the data after adjustment for place of residence indicated that the frequencies of the genotypes with the 194Trp and the 399Gln alleles were higher among urban residents (OR=3.33, 95% CL 0.48-35.90, and P=0.16 for 194Trp and OR=9.97, 95% CL 1.98-43.76, and P<0.001 for 399Gln) than among rural residents (OR=2.00, 95% CL 0.36-26.00, and P=0.30 for 194Trp and OR=1.90, 95% CL 0.50-7.53, and P=0.20 for 399Gln). These findings support our hypothesis and suggest that polymorphisms in the XRCC1 gene, in conjunction with place of residence, may modify disease risk. This first demonstration that polymorphisms in DNA repair genes may contribute to colorectal cancer susceptibility and may increase the risk of early onset of the disease opens the door for future studies in that direction.

Polymorphism of glutathione S-transferase loci GSTM1 and GSTT1 and susceptibility to colorectal cancer in Egypt.

Egypt has an unusually high proportion of early-onset colorectal cancer under age 40 years. Environmental exposures and low DNA repair capacity are among the risk factors. Because GSTM1 and GSTT1 gene deficiencies may act as risk modifiers for colorectal cancer risk, we investigated the relationship between genetic polymorphism in these genes and colorectal cancer risk in Egyptians. Sixty-six patients and 55 controls were included. Genotyping for GSTM1 and GSTT1 was conducted using PCR techniques and the results were related to epidemiologic and clinical information. No overall association was observed between GSTM1 or GSTT1 null genotypes and colorectal cancer risk. However, the data suggest a possible role for GSTM1 genotype in influencing tumor site. Furthermore, GSTM1 and GSTT1 genotypes, in conjunction with gender and place of residence, may play a role in modifying disease risk. Further studies on a larger population in Egypt are needed to generalize the results of this study.

Serum organochlorine pesticide levels in patients with colorectal cancer in Egypt.

The widespread use of pesticides in Egypt, the high incidence of colorectal cancer in Egyptian children and young adults, and the published U.S. case reports in which pesticides have been connected with colorectal cancer led the authors to investigate the possible association between organochlorines and colorectal cancer. The authors conducted a pilot study to describe serum organochlorine levels among 31 Egyptian colorectal patients and 17 controls. High levels and large interindividual variability of p,p'-dichloro-diphenyldicholoroethylene (DDE), dichloro-diphenyl-trichloroanthane (DDT), beta-hexachlorocyclohexane (beta-HCH), and hexachlorobenzene (HCB) levels were found among most subjects, especially those from rural areas. Farming and aging were each associated positively with high serum organochlorines. Colorectal cancer patients had higher serum organochlorines levels than controls. The high levels of organochlorines reported and their relation to age, residence, occupation, and disease status justify further study of the possible association between organochlorine pesticides and colorectal cancer in a larger population in Egypt.