IARC MONOGRAPHS ON THE EVALUATION OF CARCINOGENIC ...

Table 15 (contd)
Region/country No. of HCC
analysed
AFLATOXINS 231
No. with codon
249 ser mutation
Reference
Korea (Republic of) 6 0 Oda et al. (1992)
35 0 Park et al. (2000)
Singapore (Chinese) 44 0 Shi et al. (1995)
Taiwan, China 2 0 Oda et al. (1992)
12 0 Hosono et al. (1993)
Europe
France 100 2 Laurent-Puig et al. (2001)
Germany 13 0 Kress et al. (1992)
20 0 Kubicka et al. (1995)
Italy 20 0 Bourdon et al. (1995)
Spain 70 0 Boix-Ferrero et al. (1999)
United Kingdom 19 0 Challen et al. (1992)
170 0 Vautier et al. (1999)
Adapted from Stern et al. (2001)
this codon. The authors of the meta-analyses pointed out that many studies, particularly
the earlier ones, looked only for the presence or absence of the specific codon 249 ser
mutation and as a consequence may have overemphasized the importance of this particular
mutation among the total of TP53 mutations in HCC.]
The vast majority of these studies have not directly assessed either population exposure
or individual exposure to aflatoxin in relation to TP53 mutations. Instead, estimates
were made from data on aflatoxin levels in food, frequency of consumption of those
foods and extrapolation to expected aflatoxin levels based on climatic conditions likely
to promote aflatoxin production. This limits the interpretation of these data. Montesano
et al. (1997) attempted to use biomarker data on human exposure to provide information
additional to the estimates based on geographical origin of the samples.
Fujimoto et al. (1994) studied 25 HCC tissue samples from Qidong County, China,
an area of high aflatoxin exposure, and nine HCC samples from Beijing with lower aflatoxin
exposure. Thirteen of 25 tumours (52%) from Qidong carried the 249 ser mutation,
while none of the nine from Beijing did. Shimizu et al. (1999) studied 31 HCC tissue
samples from different parts of the Jiang-su province. In the northern region of this
province, where aflatoxin exposure is expected to be lower, one of 15 (8%) tumours
showed a 249 ser mutation, while in the southern part, including Haimen City, nine of 16
(56%) HCC samples showed this mutation. Scorsone et al. (1992) found the 249 ser
mutation in 21 of 36 (58%) of HCC tumour tissue samples from Qidong. In contrast, of
26 HCC examined in Hong Kong, only one (4%) had the specific 249 ser mutation,
although another tumour had a G to T transversion at the second nucleotide (Ng et al.,
1994a,b). Wong et al. (2000) found the TP53 249 ser mutation in 4/30 (13%) HCC