Tobacco and Public Health - TCSC Indonesia

426
TOBACCO USE AND RISK OF ORAL CANCER
In the US, Mashberg et al. (1993) estimated that 74% of oral cancer in this population
was attributable to smoking 6 or more cigarette equivalents per day, and 97% of the
disease was attributable to the combination of smoking and drinking. In a populationbased
case–control study of oral cancer involving 4 states in the US, Blot et al. (1988)
estimated that 80% of the oral and pharyngeal cancer cases in men and 61% in women
were attributable to smoking and alcohol drinking. Using the data from this populationbased
case–control study, Day et al. (1993) estimated that 83% of blacks and 73% of
whites developed oral cancer as a result of alcohol and/or tobacco consumption, with
most tumors arising from the combined effect of drinking and smoking. Almost half
of all oral cancer (48%) among black men was attributed to smoking one pack or more
daily in combination with heavy drinking (≥30 drinks per week). For white men, 36%
of oral cancers were accounted for by this level of smoking and drinking. Tobacco
and alcohol consumption account for bulk of the racial and gender differences in oral
cancer in the US.
In Beijing, China, Zheng et al. (1990) found that tobacco smoking accounts for about
34% of all cases of oral cancer in the Chinese population (45% among males and 21%
among females) and 44% of all oral squamous-cell carcinoma. In Bombay, it is estimated
that 70% of oral cancer cases were attributable to smoking and chewing tobacco.
Biological plausibility
Tobacco smoke is a complex mixture of compounds. Over 300 carcinogens have been
identified in cigarette smoke. Polycyclic aromatic hydrocarbons (PAHs) have long been
recognized as carcinogens present in tar. There are about 20–40 ng of benz-pyrene per
cigarette and substantial levels of carcinogenic metals such as hexavalent chromium
(Johnson 2001). The most important and abundant carcinogenic agents in tobacco
smoke are the tobacco-specific N-nitrosamines (TSNA), including nitrosonornicotine
(NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK).
About 30 carcinogens have been identified in smokeless tobacco. Again, the TSNAs
are major contributors to the carcinogenic activity of these types of tobacco (Hoffman
and Djordjevic 1997). TSNAs are formed exclusively from nicotine and from the
minor tobacco alkaloids, primarily formed after harvesting the leaves, during
drying, curing, aging, and especially during fermentation (Hoffmann et al. 1994;
Brunnemann et al. 1996).
The absorbed PAHs, TSNA, and aromatic amines from tobacco use can be metabolically
activated to form electrophilic intermediates, which have the ability to react with
DNA to form covalently bound DNA adducts, which interfere with DNA replication
and initiate the carcinogenesis process. Oral swabbing of a low concentration of a mixture
of NNN plus NNK in water induces oral tumors in rats (Hoffman and Djordjevic 1997).
In vitro assays have shown that human buccal mucosa has the capability to metabolize
NNK and NNN to alkyldiazohydroxides that can react with DNA as reviewed by Gupta
et al. (1996). DNA adducts play a crucial role in tobacco-induced carcinogenesis and