Hepatitis: Parkin DM

Sitas F, Parkin DM, Chirenje M, Stein L, Abratt R, Wabinga H. · Research Division, The Cancer Council New South Wales, Australia. · Lancet Oncol. · Pubmed #18672214 No free full text.

Abstract: Africa has contributed substantial knowledge to the understanding of certain risk factors for cancer, such as the role of several infectious agents (eg, viruses, bacteria, and parasites), aflatoxins, and certain lifestyle factors. Although the relative importance of many lifestyle factors is becoming better understood in developed countries, more work is needed to understand the importance of these factors in different African settings. In view of the substantial genetic diversity in Africa, it would be prudent not to generalize too widely from one place to the next. We argue that risks for several exposures related to certain cancers differ from the patterns seen in developed countries. In this paper, we review the current knowledge of causes of some of the leading cancers in Africa, namely cancers of the cervix, breast, liver, prostate, stomach, bladder, and oesophagus, Kaposi's sarcoma, non-Hodgkin lymphoma, and tobacco-related cancers. There are no comprehensive cancer-control programmes in Africa and provision of radiotherapy, chemotherapy, and palliation is inadequate. Certain cost-effective interventions, such as tobacco control, provision of antiretroviral therapy, and malarial and bilharzial control, can cause substantial decreases in the burden of some of these cancers. Vaccinations against hepatitis B and oncogenic human papilloma viruses can make the biggest difference, but very few countries in Africa can afford these vaccines without substantial subsidization.

Chen JG, Parkin DM, Chen QG, Lu JH, Shen QJ, Zhang BC, Zhu YR. · Qidong Liver Cancer Institute, Qidong, Jiangsu, China. · J Med Screen. · Pubmed #14738659 No free full text.

Abstract: OBJECTIVES: To investigate the effectiveness of screening for liver cancer in reducing mortality from the disease in a high-risk population in China. SETTING: A randomised controlled trial was carried out among men aged 30-69 who were chronic carriers of hepatitis-B virus (HBsAg positive) during the period 1989-1995 in Qidong county, Jiangsu Province, China. METHODS: 5581 HBsAg carriers were identified by population screening and randomly assigned to a screening group (group A, 3712 men), and controls (group B, 1869 men). Screening was planned to be six monthly alpha-fetoprotein (AFP) assays, with follow-up of subjects having an abnormal (>/=20 micrograms/l) test. All subjects were followed up for liver cancer and/or death until 31 December 1995. RESULTS: The overall sensitivity and specificity of the programme was 55.3% and 86.5%, respectively; in subjects who complied with all scheduled screening tests, the values were 80.0% and 80.9%. Three hundred and seventy-four primary liver cancer (PLC) cases were diagnosed. The percentage of cases in stage I was significantly higher in group A (29.6%) than in group B (6.0%). The one-, three-, and five-year relative survival rates were 23.7%, 7.0%, and 4.0% in group A, and 9.7%, 4.0%, and 4.1% in group B respectively, with no difference in five-year survival between the groups. The mortality rate in the screened group (1138 per 100,000 person-years) was not significantly different from that in the controls (1114 per 100,000). A Poisson regression model showed that the probability of death (rate ratio) in the screening group was 0.83 (95% CI 0.68-1.03) relative to the control group. CONCLUSIONS: Screening with AFP resulted in earlier diagnosis of liver cancer, but the gain in lead time did not result in any overall reduction in mortality, because therapy for the patients found by screening was ineffective. Further studies using improved methods of screening, diagnosis and treatment are indicated.

Szymañska K, Chen JG, Cui Y, Gong YY, Turner PC, Villar S, Wild CP, Parkin DM, Hainaut P. · IARC, Lyon Cedex 08, France. · Cancer Epidemiol Biomarkers Prev. · Pubmed #19366907 No free full text.

Abstract: Hepatocellular carcinoma (HCC) has a high mortality in East Asia and Sub-Saharan Africa, two regions where the main etiologic factors are chronic infections with hepatitis B virus and dietary exposure to aflatoxin. A single base substitution at the third nucleotide of codon 249 of TP53 (R249S) is common in HCC in these regions and has been associated with aflatoxin-DNA adducts. To determine whether R249S may be detected in plasma DNA before HCC diagnosis, we conducted a case-control study nested in a cohort of adult chronic hepatitis B virus carriers from Qidong County, People's Republic of China. Of the 234 plasma specimens that yielded adequate DNA, only 2 (0.9%) were positive for R249S by restriction fragment length polymorphisms, and both of them were controls. Of the 249 subjects tested for aflatoxin-albumin adducts, 168 (67%) were positive, with equal distribution between cases and controls. Aflatoxin-albumin adduct levels were low in the study, suggesting an overall low ongoing exposure to aflatoxin in this cohort. The R249S mutation was detected in 11 of 18 (61%) available tumor tissues. To assess whether low levels of mutant DNA were detectable in pre-diagnosis plasma, 14 plasma specimens from these patients were analyzed by short oligonucleotide mass analysis. Nine of them (64%) were found to be positive. Overall, these results suggest that HCC containing R249S can occur in the absence of significant recent exposure to aflatoxins. The use of short oligonucleotide mass analysis in the context of low ongoing aflatoxin exposure may allow the detection of R249S in plasma several months ahead of clinical diagnosis.

Parkin DM. · Clinical Trials Service Unit and Epidemiological Studies Unit, University of Oxford, Headington, UK. · Int J Cancer. · Pubmed #16404738 No free full text.

Abstract: Several infectious agents are considered to be causes of cancer in humans. The fraction of the different types of cancer, and of all cancers worldwide and in different regions, has been estimated using several methods; primarily by reviewing the evidence for the strength of the association (relative risk) and the prevalence of infection in different world areas. The estimated total of infection-attributable cancer in the year 2002 is 1.9 million cases, or 17.8% of the global cancer burden. The principal agents are the bacterium Helicobacter pylori (5.5% of all cancer), the human papilloma viruses (5.2%), the hepatitis B and C viruses (4.9%), Epstein-Barr virus (1%), human immunodeficiency virus (HIV) together with the human herpes virus 8 (0.9%). Relatively less important causes of cancer are the schistosomes (0.1%), human T-cell lymphotropic virus type I (0.03%) and the liver flukes (0.02%). There would be 26.3% fewer cancers in developing countries (1.5 million cases per year) and 7.7% in developed countries (390,000 cases) if these infectious diseases were prevented. The attributable fraction at the specific sites varies from 100% of cervix cancers attributable to the papilloma viruses to a tiny proportion (0.4%) of liver cancers (worldwide) caused by liver flukes.

Bah E, Parkin DM, Hall AJ, Jack AD, Whittle H. · International Agency for Research on Cancer, c/o The Gambia Hepatitis Intervention Study, MRC Laboratories, Fajara PO. Box 273, Banjul, The Gambia. · Br J Cancer. · Pubmed #11336472 links to  free full text

Abstract: We describe the incidence of cancer in The Gambia over a 10-year period using data collected through the Gambian National Cancer Registry. Major problems involved with cancer registration in a developing country, specifically in Africa are discussed. The data accumulated show a low overall rate of cancer incidence compared to more developed parts of the world. The overall age standardized incidence rates (ASR) were 61.0 and 55.7 per 100 000 for males and females, respectively. In males, liver cancer was most frequent, comprising 58% of cases (ASR 35.7) followed by non-Hodgkin lymphoma, 5.4% (ASR 2.4), lung 4.0%, (ASR 2.8) and prostate 3.3% (ASR 2.5) cancers. The most frequent cancers in females were cervix uteri 34.0% (ASR 18.9), liver 19.4% (ASR 11.2), breast 9.2% (ASR 5.5) and ovary 3.2% (ASR 1.6). The data indicate that cancers of the liver and cervix are the most prevalent cancers, and are likely to be due to infectious agents. It is hoped that immunization of children under 1 year against hepatitis B will drastically reduce the incidence of liver cancer in The Gambia.