Dietary iron overload as a risk factor for hepatocellular carcinoma in black africans

Mandishona, Eberhard; Macphail, A. P.; Gordeuk, Victor R.; Kedda, Mary Anne; Paterson, Alan C.; Rouault, Tracey A.; Kew, Michael C.

doi:10.1002/hep.510270614

Cited by 160 publications

(79 citation statements)

References 26 publications

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“…Two such studies from the United States and Sweden showed a strong association of HCC and HH [64,135]. In addition to HH, the hepatic iron overload owing to other causes, such as homozygous beta thalassemia [136] and the dietary form observed in South African blacks [137], is also associated with an increased risk of HCC. There is also evidence that marked iron overload in the setting of end-stage liver disease is also associated with HCC.…”

Section: Hemochromatosis and Hccmentioning

confidence: 99%

Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma

et al. 2010

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Introduction The Asian Pacific Association for the Study of the Liver (APASL) convened an international working party on the management of hepatocellular carcinoma (HCC) in December 2008 to develop consensus recommendations. Methods The working party consisted of expert hepatologist, hepatobiliary surgeon, radiologist, and oncologist from Asian-Pacific region, who were requested to make drafts prior to the consensus meeting held at Bali, Indonesia on 4 December 2008. The quality of existing evidence and strength of recommendations were ranked from 1 (highest) to 5 (lowest) and from A (strongest) to D (weakest), respectively, according to the Oxford system of evidence-based approach for developing the consensus statements. 123Hepatol Int (2010) 4: 439-474 DOI 10.1007/s12072-010-9165-7 Results Participants of the consensus meeting assessed the quality of cited studies and assigned grades to the recommendation statements. Finalized recommendations were presented at the fourth APASL single topic conference on viral-related HCC at Bali, Indonesia and approved by the participants of the conference.

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Section: Hemochromatosis and Hccmentioning

confidence: 99%

Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma

et al. 2010

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“…Mandishona et al in 1998 reported a relative risk of HCC development of 10.6 (95% confidence intervals 1.5-76.8) in black patients in southern Africa with dietary iron overload, after adjusting for the confounding effects of chronic HBV or hepatitis C virus (HCV) infections, cirrhosis, and dietary exposure to aflatoxin B 1 [42]. A similar observation was made in two additional sub-Saharan African studies after allowing for the confounding effects of cirrhosis, although the confounding effects of HBV and HCV were not taken into consideration in these studies [43,44].…”

Section: Hepatocellular Carcinoma In Dietary Iron Overloadmentioning

confidence: 99%

Hepatic iron overload and hepatocellular carcinoma

Kew

2009

Cancer Letters

Self Cite

108

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In recent years it has become increasingly evident that excess body iron may be complicated by the supervention of hepatocellular carcinoma (HCC). Hereditary hemochromatosis (HH) was the first condition in which hepatic iron overload was shown to predispose to the development of HCC. The inherited predisposition to excessive absorption of dietary iron in HH is almost always the result of homozygosity of the C282Y mutation of the HFE gene, which causes inappropriately low secretion of hepcidin. HCC develops in 8-10% of patients with HH and is responsible for approximately 45% of deaths in the HCC patients. Cirrhosis is almost always present when HCC is diagnosed. Dietary iron overload is a condition which occurs in rural-dwelling Black Africans in southern Africa as a result of the consumption, over time, of large volumes of alcohol home-brewed in iron containers and having, as a consequence, a high iron content. Iron loading of the liver results and may be complicated by malignant transformation of the liver (relative risk of approximately 10.0). Accompanying cirrhosis does occur but is less common than that in HH. The development of HCC as a consequence of increased dietary iron, and the fact that it may develop in the absence of cirrhosis, has been confirmed in an animal model. Drinking water with a high iron content might contribute to the high incidence of HCC in parts of Taiwan. The metabolic syndrome [obesity, insulin resistance type 2 (or diabetes mellitus type 2), non-alcoholic fatty liver or non-alcoholic steatohepatitis] has in recent years become a major public health problem in some resource-rich countries. A link between excess body iron and insulin resistance or the metabolic syndrome has become apparent. The metabolic syndrome may be complicated by the supervention of HCC, and recent evidence suggests that increased body iron may contribute to this complication.

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“…Previous studies in Africa are limited to ecological studies comparing regional HCC rates to estimated aflatoxin intake (Autrup et al, 1987;Omer et al, 1998;van Rensburg et al, 1990). Three small case-control studies of HCC in Africa have assessed aflatoxin exposure at the individual level, with equivocal results (Olubuyide et al, 1993;Mandishona et al, 1998;Omer et al, 2001). In the Gambia, levels of aflatoxin-albumin adducts in the serum have been validated to reflect the intake of foods contaminated with AFB1 Wild and Hudson et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

249ser TP53 mutation in plasma DNA, hepatitis B viral infection, and risk of hepatocellular carcinoma

Lesi²,

et al. 2005

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Hepatocellular carcinoma (HCC) from regions with high dietary exposure to aflatoxins and endemic for hepatitis B virus (HBV) often contain a specific mutation at codon 249 in TP53 (249 ser ; AGG to AGT, Arg to Ser). This mutation is also detectable in circulating cell-free DNA from the plasma of HCC patients and healthy subjects in these regions. We have examined the joint effect of plasma 249 ser and HBV infection in a case-control study design involving 348 control, 98 cirrhotic, and 186 HCC participants from The Gambia, West Africa, an area of high HCC incidence. The 249 ser mutation was detected in 3.5% of controls, 15.3% of cirrhotics, and 39.8% of HCC cases (adjusted odds ratios (OR): 4.83, (95% confidence interval (CI): 1.71-13.7) for cirrhosis and 20.3 (8.19-50.0) for HCC). HBsAg positivity along with plasma 249 ser was observed in 45/183 (24.6%) HCC cases compared to only one (0.3%) control. Risk for HCC was associated with markers of HBV alone (OR: 10.0, 95% CI: 5.16-19.6), 249 ser alone (OR: 13.2, 95% CI: 4.99-35.0), and both markers present (OR: 399, 95% CI: 48.6-3270). These results suggest a multiplicative effect on HCC risk resulting from the mutational effect of aflatoxin on TP53, as monitored by detection of plasma 249 ser , with concomitant chronic infection with HBV.

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Dietary iron overload as a risk factor for hepatocellular carcinoma in black africans

Cited by 160 publications

References 26 publications

Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma

Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma

Hepatic iron overload and hepatocellular carcinoma

249ser TP53 mutation in plasma DNA, hepatitis B viral infection, and risk of hepatocellular carcinoma

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