world cancer report - iarc

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