Tobacco and Public Health - TCSC Indonesia

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TOBACCO USE AND RISK OF ORAL CANCER
products (Franco et al. 1989; Zheng et al. 1990; Bundgaard et al. 1994; Schidt 1998), or
daily or weekly or monthly consumption of the products (Rothman and Keller 1972;
Wynder et al. 1976; Elwood et al. 1984; Blot et al. 1988; Tuyns et al. 1988; Merletti
et al. 1989; Franceschi et al. 1990; Day et al. 1993; Mashberg et al. 1993; Kabat et al.
1994; Andre et al. 1995; Chyou et al. 1995; Franceschi et al. 1999; Hayes et al. 1999;
Garrote et al. 2001), or by cumulative tar/amount of alcohol day (Muscat et al. 1996),
or expressed by other means (Baron et al. 1993; Lewin et al. 1997; De Stefani et al. 1998;
Zavras et al. 2001).
A strong interaction between smoking and alcohol use on the risk of oral cancer is
exemplified from the study by Franceschi et al. (1999) in Italy. In this study, the highest
level of risk of oral cancer (OR = 227.8, 95% CI 54.6–950.7) was observed among those
most heavily consuming both tobacco and alcohol.
Tobacco and gene interaction
It is suggested that functional polymorphisms in genes encoding tobacco carcinogenmetabolizing
enzymes may modify the relationship between tobacco smoking and an
individual’s oral cancer risk. This is biologically plausible since the phase I enzymes
(cytochromes P-450) activate many tobacco procarcinogens by forming or exposing
their functional groups. For example, CYP1A1 is the major enzyme responsible for the
metabolic activation of benzo-(a)-pyrene and other polycyclic aromatic hydrocarbons
(PAHs), and CYP2E1 is the major enzyme responsible for the metabolic activation
of nitrosamines. The activated carcinogens can bind covalently to DNA to form DNA
adducts. Accumulation of DNA adducts at critical loci such as oncogenes or tumor
suppressor genes can lead to somatic mutation and disruption of the cell cycle (Geisler
and Olshan 2001).
The phase II enzymes (such as the glutathione S-transferases (GSTs) and N-acetyl
transferase (NATs)) are involved in the detoxification of activated metabolites of
carcinogens by phase I enzymes. GSTM1, for instance, metabolizes and detoxifies
benzo-(a)-pyrene-diol epoxides (14,15), while GSTT1 detoxifies epoxides and other
constituents of tobacco smoke, such as alkyl halides (16,17). Therefore, individuals
who have high phase I metabolizing activities but have low or lack certain phase II
metabolizing activity, may accumulate more DNA adducts, and thus have a particularly
high cancer risk after exposure to tobacco smoke (13,18,19).
A few recent studies have investigated the association between tobacco smoking,
genetic polymorphisms, and oral cancer risk [11,20–26]. For example, Park et al. (1999)
reported a greater risk for those with the GSTP1 (var/var) genotype who were exposed
to low levels of smoking (i.e. ≤20 pack-years, OR = 3.4, 95% CI 1.1–11) than among
heavier smokers (i.e. >20 pack-years, OR = 1.4, 95% CI 0.5–4.0), suggesting GSTP1
genotype may play a role in risk for oral cancer particularly among lighter smokers.
The studies by Sato et al. (1999, 2000) also showed that individuals with a combined
genotype of Val/Val and GSTM1(–) were at an increased risk for oral squamous-cell