Tobacco and Public Health - TCSC Indonesia

376
LARYNGEAL CANCER
RR
100
10
1
0.1
NS (Ref)
1–7 cpd
8–15 cpd
16–25 cpd
26�cpd
Dosemeci et al. 1997). Without exception, relative risks are higher for supraglottic than
for glottic cancer, which is compatible with a direct contact mechanism of tobacco
carcinogenicity on the organ. As an example, Fig. 21.4 reports the results of the largest
available study from four European countries.
Limited data are available on the synergism between tobacco smoking and alcohol
drinking on cancer in different parts of the organ (Dosemeci et al. 1997; Guenel et al.
1988): although risk estimates are often unstable due to small numbers, it is suggested
that the combined effect of the two exposures on glottic cancer is compatible with a
multiplicative model of interaction, while for supraglottic cancer the combined relative
risks are lower than expected according to the multiplicative model, suggesting some
overlap in the carcinogenic action of the two agents.
Evidence from mechanistic studies
NS (Ref)
1–7 cpd
8–15 cpd
16–25 cpd
glottic cancer supraglottic cancer
RR, relative risk; NS, non-smoker; cpd, cigarettes per day
26�cpd
Fig. 21.4 Relative risk of glottic and supraglottic cancer from cigarette smoking—Europe
(Tuyns et al. 1988).
Mutation in the p53 gene is a common genetic alteration in laryngeal cancer. A distinct
pattern of mutations has been reported in cancer of the larynx, and in other tobaccorelated
cancers, as compared to non-tobacco related cancers. This includes a higher
proportion of tumours harbouring a mutation and a higher proportion in G–T transversions,
in particular at codons 157, 158, 179, and 249. These mutations likely reflect
the effect of the interaction of tobacco carcinogens, such as BPDE, the active metabolite
of benzo(a)pyrene, on the DNA (Brennan and Boffetta in press). The evidence directly
linking tobacco smoking to p53 mutation in laryngeal carcinogenesis, however, is
weak. Out of 171 p53 mutations reported in laryngeal cancers in the IARC p53 database
(www.iarc.fr/p53/index.html), data on smoking habit were available for 73 patients, of
whom only 3 were non-smokers.