Liver cancer epidemiology and risk factors in South Africa

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Date

2019

Authors

Wei-Hong Mak, Daniel

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Abstract

Primary liver cancer (LC) in South Africa (SA) is a public health concern; it is currently the seventh leading cause of death among SA men and women after colon cancer according to GLOBOCAN 2018. Despite this, publications of this disease remains scarce, if not absent. Accordingly, trend analysis for LC incidence (from 1993-2012) and mortality (from 1999-2015) rates demonstrated an overall decrease in SA, and these trends varied between different sex-, age- and population-subgroups. Specifically, rates markedly increased in the middle-aged black African women in the recent years. LC risk was highest in black African men in their early 30s, and survival from this malignancy provided a dismal outlook as most patients were only diagnosed during autopsy rather than during hospital and/or clinic consultations. Barring this, these findings demonstrate the utility of mortality data in supplementing the cancer registries for cancer that progress quickly. Liver cancer has several types, each originate from various type of cells that becomes cancerous. Hepatocellular carcinoma (HCC) accounts for the majority of liver cancers and originates from hepatocellular cells. The study of 150 HCC patients and 438 non-HCC cancer controls showed that risk factors that were significantly associated with HCC include: rural birthplace, male sex and living in an urban area for <14 years, Hepatitis B virus (HBV) DNA levels (>2000-≥200,000 IU/ml) and antibodies against hepatitis C virus (anti-HCV) positivity. Interestingly, human immunodeficiency virus (HIV) infection alone did not confer any risk in developing HCC, nor did it synergistically interact with HBV infection. Comparably, lifestyle-related risk factors (alcohol consumption, tobacco smoking, number of sexual partners, diabetes and hormonal contraceptive use) were not associated with HCC risk. Phylogenetic analyses of the HBV isolates from the HCC patients and non-HCC controls demonstrated that HBV subgenotypes included A1 (90.7%), A2 (2.3%) and A3 (7%). Core promoter mutations (T1753V, A1762T and G1764A), preS deletions, ps2F22L, and preS2 start codon mutations were associated with HCC development, and the combination of which may potentially assist in the development of more targeted screening in high-risk groups. In view of these findings, this work provides much needed analysis of LC trends in SA and provides a critical assessment of current control strategies, or gaps, in the prevention of and interventions for LC in SA. Moreover, this work pays particular attention to the consolidation of what is an overview of LC in SA by reporting various aspects: incidence, mortality, demographics, viral and non-viral risk factors and a combination of HBV mutations as biomarkers.

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Thesis submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in fulfilment of the requirements for the degree of Doctor of Philosophy. November 2019

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Mak, Daniel Wei-Hong, Liver cancer epidemiology and risk factors in South Africa, University of the Witwatersrand, Johannesburg, <http://hdl.handle.net/10539/29762>

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