Letters 937 Hepatocellular carcinoma and African We entirely support the authors in their hepatocellular carcinoma (HCC) and the tox- iron overload urge that prospective studies should be icity of iron overload in Africa. undertaken to examine the possible role of High quality cancer epidemiological data EDITOR,-Gangaidzo and Gordeuk (Gut African overload in the pathogenesis of HCC. are difficult to come by in Africa. With regard 1995; 37: 727-30) postulate that iron over- However, at the village level, in the requisite to the estimate ofDrs Walker and Segal offive load may be a risk factor for hepatocellular studies, major difficulties will be encountered admissions for HCC per 100 000 population Gut: first published as 10.1136/gut.38.6.937-a on 1 June 1996. Downloaded from carcinoma (HCC) - a subject of obvious regarding participation, especially regarding annually in rural South Africa, we note that interest to workers in Africa. It is especially so blood taking and the fear of AIDS. A compli- hospital based studies may be unreliable to one of us (AW) who, originally, in 1953, cating factor for HCC, as Kew and associates9 estimates of countrywide incidence rates.' propounded the iron overload hypothesis. have shown, is that the infection rate of HBV, HCC is a common and important condition This sought to explain the abnormal iron an important aetiological factor, varies not in Africa. At least one authority has observed, deposition (siderosis) present in many only from region to region, but from village to with regard to HCC, that 'some of the docu- Africans, caused by a high adventitious intake village. Additionally, there will be the usual mented incidences are almost certainly of the element arising from food preparation difficulties in seeking to resolve whether iron underestimates, perhaps by as much as 50 in iron utensils.' overload, if implicated, is a causative or an percent in some countries'.2 A contemporary In comment, firstly, the above authors state associated factor. Not least of perplexities textbook of gastroenterology in the tropics that HCC is probably the commonest malig- is the situation whereby a given parameter, offers an adjusted rate for HCC of 113 per nancy occurring in men worldwide. Actually for example, serum ferritin concentration, 100 000 per annum in Shangaan men inhab- it ranks eighth in numerical importance on a can have a differing significance according to iting the border areas of Mozambique, worldwide basis, accounting for 5-3% of new the context. As a recent example of this Zimbabwe, and South Africa.2 In Harare, cancers in men and 2-6% in women.2 phenomenon, at Belfast and Toulouse, there Zimbabwe, HCC is the most common malig- Next, it is insufficiently appreciated that its is the same average serum cholesterol value nancy in men in the 1990s (Harare Cancer incidence in men in Africa is highly variable, but a fourfold difference in mortality from Registry, 1995). In the internal medicine ranging from 47-9 per 100 000 world popula- coronary heart disease.'0 wards of one of us (ITG) at Harare Central tion, in Mali,3 to 7-5 in Uganda,4 and 6.4 in Finally, should iron overload be meaning- Hospital, HCC was the most common cancer South Africa.5 In agreement with the latter, fully incriminated, the authors say 'it is diagnosis in men in 1993-1994 and recently, in three rural widely separated eminently preventable through changing the accounted for 3-2% of admissions. Among hospitals, responsible for the needs of about practices of preparation and consumption of those of us who regularly provide medical 400 000 Africans, we found an average offive traditional beer, and it is treatable by phlebot- care to rural Africans (constituting more than admissions of men for HCC per 100 000 omy therapy to remove iron from the body'. 80% of the Zimbabwean population), there is annually. Interestingly, the latter rates are In our view, both ofthe suggested procedures, general agreement that HCC represents a much the same as those of Afro-Americans, in the rural context, are non-starters. major health problem. We have seen 'few 50-6.6 per 100 000.3 The citing of 100 cases To reiterate, while we are unconvinced of more depressing tasks than caring for a per 100 000 in Mozambique is inapposite as the clinical importance of iron overload, the patient with this particular malignancy, no current study ofthe painstaking type made issue must be resolved - that is, whether it is and there is no satisfactory treatment'.3 in Uganda,4 has been pursued in or is not of public health significance within The question of whether iron overload in Mozambique - a country at war for 20 years. the context of impoverished Africa. Africa is 'noxious', seems to recapitulate the We know of no present day excessively high A R P WALKER discussion of 30 years ago about whether iron rates for HCC in African countries south of Human Biochemistry Research Unit, overload is damaging in people of European Department of Tropical Diseases, origin with hereditary haemochromatosis. As the Equator. School ofPathology ofthe of iron we learn more about states of excess iron, it is Turning now to the noxiousness University ofthe Witwatersrand, and the http://gut.bmj.com/ overload, in the original hypothesis,' also South African Institutefor Medical Research, our opinion that the weight ofevidence points on 296 Johannesburg, to the conclusion that iron overload of what- in a subsequent local study based South Africa postmortem examinations at Baragwanath ever cause (HLA linked hemochromatosis, Hospital, Soweto, Johannesburg,6 the patho- ISIDOR SEGAL transfusions, ineffective erythropoiesis, or Gastroenterology Unit, dietary iron in Africa) is potentially toxic, genicity of iron overload was doubted, for no Baragwanath Hospital high constant correlation was found between the and University ofthe Witwatersrand, and that medical practitioners are obligated to degrees of fibrosis and cirrhosis and the Johannesburg, work to prevent and treat iron overload in amount ofiron pigment in the liver. However, South Africa their patients.4 In a series of careful patholog- ical studies 35 years ago, Professor T H on September 28, 2021 by guest. Protected copyright. later, at the same hospital, as recently detailed 1 Walker ARP, Arvidsson UB. Iron 'overload' in by Lynch,7 associations were reported of the South African Bantu. Trans R Soc Trop Bothwell and colleagues at the University siderosis with osteoporosis, diabetes, oeso- Med Hyg 1953; 47: 536-48. of the Witwatersrand provided convincing 2 Tomatis L. Cancer: causes, occurrence and control. evidence that dietary iron overload directly phageal cancer, and heart failure. The find- International Agency for Research on Cancer, ings in these studies, however, made over 20 IARC Scientific Publications No 100. Lyon: causes cirrhosis.5-7 Interestingly, in 1960 years ago, have not been currently confirmed. World Health Organization, 1990: 59. Bothwell reported that in Africans the hepatic More to the point, over the decades, no 3 Parkin BM, Muir CS, Whelan SL, et al. Cancer iron threshold above which portal fibrosis and incidence infive continents. Vol 6. Lyon: IARC, are to be is a concen- attempt has been made at the village level to 1992: 930. cirrhosis likely present learn whether iron overload contributes 4 Wabinga HR, Parkin DM, Wabwire-Mangen F, tration of 360 ,umol/g dry weight5 (normal is and that Mugerwa JW. Cancer in Kampala, Uganda, in less than 30 ,umol/g dry weight). Twenty six significantly to morbidity mortality; in the era of is, is it disadvantageous to 1 per 100, or 1 per 1989-91: changes in incidence years later Dr L Powell's group in Australia AIDS. Int_J Cancer 1993; 54: 26-36. for 1000? 5 Sitas F, Pacella R. Cancer regist"y ofSouth Africa, reported an almost identical threshold In an investigation made in 1985 by 1989. Johannesburg: South African Institute hepatic damage among white subjects with Gordeuk et a18 in Zimbabwe, it was estimated for Medical Research, 1994: 33. hereditary hemochromatosis.8 Support for the 6 Higginson J, Gerritsen Th, Walker ARP. African iron overload that there were about 80 000 cases of severe Siderosis in the Bantu of Southern Africa. association between iron overload. In the same year, it was stated Am JPathology 1953; XXIX: 779-815. and cirrhosis is provided by a study con- that in that country there were 14 587 cases of 7 Lynch SR. Iron overload: prevalence and impact ducted in the late 1980s at a mission hospital on health. Nutr Rev 1995; 53: 255-60. in Swaziland: nine of 29 consecutive adults malaria, 2956 of tuberculosis, and 144 of 8 Gordeuk VR, Boyd RD, Brittenham GM. cholera. Surely, were iron overload as patho- Dietary iron overload persists in rural sub- undergoing diagnostic liver biopsy had gnomonic as is conjectured, there should be a Saharan Africa. Lancet 1986; i: 1310-3. hepatic iron concentrations over 360 ,ug/g plethora of evidence incriminating it. This 9 Kew MC. Chronic hepatitis B virus infection dry weight and seven of these subjects (78%) and hepatocellular carcinoma in Africa. SAfrJ fibrosis or cirrhosis on does not seem to be the case. Sci 1992; 88: 524-8. had either portal Gangaidzo and Gordeuk regret that in 10 Evans AE, Ruidavets J-B, McCrum EE, et al. histological examination.9 Africa, only about half of the cases of HCC Autres pays, autres coeurs? Dietary patterns, Two recent studies that we have conducted risk factors and ischaemic heart disease in examine the noxiousness of dietary iron over- are explicable on the basis of HBV infection. Belfast and Toulouse. Q Jf Med 1995; 88: It must be recognised that apart from the 469-77. load in data sets that span the historical spec- cause and effect of classic deficiency diseases, trum of this disease.