world cancer report - iarc
world cancer report - iarc
world cancer report - iarc
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AFLATOXIN B 1<br />
HEPATITIS VIRUS<br />
(chronic active hepatitis)<br />
mutation at codon 249 in the p53 gene<br />
(AGG to AGT, arginine to serine) (Fig. 2.28).<br />
This mutation is rarely found in hepatocellular<br />
carcinomas in areas of low aflatoxin<br />
exposure, but occurs in up to 60% of hepatocellular<br />
carcinomas in regions of very<br />
high exposure to aflatoxins [3]. Naturally<br />
occurring aflatoxins are categorized by<br />
IARC as Group 1 carcinogens (causing <strong>cancer</strong><br />
in humans).<br />
44 The causes of <strong>cancer</strong><br />
Metabolic host factor<br />
(Cytochrome P450s)<br />
Fig. 2.28 Interaction between aflatoxin B 1 and HBV infection in the pathogenesis of human hepatocellular carcinoma.<br />
Fig. 2.29 The fungi Aspergillus and Penicillium<br />
produce ochratoxins in humid conditions on commodities<br />
used for the production of human or animal<br />
food.<br />
Electrophilic<br />
metabolite<br />
Detoxification<br />
(Glutathione transferase)<br />
Aflatoxin-glutathione conjugate<br />
Promutagenic<br />
DNA lesion<br />
p53 gene mutation<br />
(G:T-T:A transversion)<br />
Fusarium<br />
Fusarium verticillioides (previously F.<br />
monoliforme), which is ubiquitous on<br />
maize, produces the toxins fumonisin B 1<br />
and B 2 and fusarin C, under warm dry conditions.<br />
Incidence of oesophageal <strong>cancer</strong><br />
incidence has been related to the occurrence<br />
of F. verticillioides or its toxins in<br />
maize. Fusarium sporotrichioides produces<br />
T-2 toxin, which may have played a<br />
significant role in large-scale human poisonings<br />
in Siberia in the last century and<br />
may be carcinogenic [4].<br />
Ochratoxin<br />
Ochratoxin A, also a fungal metabolite (Fig.<br />
2.29), has been classed as a possible<br />
human carcinogen. This mycotoxin may<br />
contaminate grain and pork products and<br />
has been detected in human blood and<br />
milk. Several studies have suggested correlations<br />
between ochratoxin A and Balkan<br />
endemic nephropathy and between geographical<br />
distribution of Balkan endemic<br />
nephropathy and high incidence of urothelial<br />
urinary tract tumours. In mice, administration<br />
of ochratoxin A causes increased<br />
incidence of hepatocellular carcinomas<br />
and other tumour types [4,5].<br />
Pyrrolizidine alkaloids<br />
Pyrrolizidine alkaloids (including lasiocarpine<br />
and monocrotaline) are naturally<br />
occurring plant toxins which may be<br />
ingested by animals, and by humans eat-<br />
Selective clonal<br />
expansion and p53<br />
allelic deletion<br />
CELL PROLIFERATION<br />
HBV-X protein - interacts with p53 or Rb protein<br />
- transcriptional activation of MYC oncogene<br />
HEPATOCELLULAR<br />
CARCINOMA<br />
ing some medicinal plants (e.g. comfrey)<br />
or honey, in some areas [6]. Several<br />
pyrrolizidine alkaloids have been found to<br />
cause DNA damage and show mutagenic<br />
properties in vitro. Chronic consumption<br />
of some pyrrolizidine alkaloids may cause<br />
liver tumours in rodents, but has not been<br />
associated with <strong>cancer</strong> in humans.<br />
Bracken<br />
Animals grazing on bracken (genus<br />
Pteridium) may show various signs of toxicity,<br />
including tumours in the upper gastrointestinal<br />
tract and bladder, which are<br />
attributable to the carcinogen ptaquiloside<br />
[7]. The corresponding glucoside may<br />
be present in bracken at a concentration<br />
of 13,000 ppm. Metabolism of this compound<br />
gives rise to alkylation adducts in<br />
DNA. Milk from cows fed on bracken fern<br />
causes <strong>cancer</strong> in experimental animals.<br />
Bracken may pose a carcinogenic hazard<br />
for humans in population identified as<br />
exposed in Japan, Costa Rica and the<br />
United Kingdom.<br />
Contamination by industrial chemicals<br />
Certain organochlorines, including DDT<br />
and other pesticides, are resistant to<br />
degradation, are very lipid-soluble and<br />
hence persist in the environment and<br />
are bioconcentrated up the human food<br />
chain. Related industrial chemicals such<br />
as polychlorinated biphenyls are subject<br />
to the same effect. DDT and a number of