Tobacco and Public Health - TCSC Indonesia

646
TOBACCO AND ALCOHOL INTERACTION
and cigarette smoke. Target organs included the esophagus, the lung, and the
heart. At each organ site, the damage induced by combined exposure to alcohol and
cigarette smoke was greater than the DNA damage induced by smoke or alcohol
alone (Izzotti et al. 1998). In human studies, both alcohol consumption and tobacco
are associated with p53 mutations in non-small cell lung cancer, compatible
with the possibility that alcohol enhances mutagenicity induced by tobacco smoke
(Ahrendt et al. 2000).
Alcohol is not considered to be a carcinogen, but more likely acts as a co-carcinogen
or a tumor promoter to increase the toxic effects of tobacco-specific carcinogens such
as N-nitrosoamines (Hecht 1999). Another mechanism of action of alcohol metabolism
possibly leading to cancer relates to the formation of acetaldehyde and to highly
reactive free radicals. Acetaldehyde has greater cellular toxicity than alcohol and could
induce DNA damage or interfere with DNA repair mechanisms (Homann et al. 2000)
For some organs, such as the mouth or the esophagus, alcohol could increase the permeability
of mucous membranes to tobacco-specific carcinogens (Du et al. 2000). Finally,
heavy consumption of alcohol can be associated with nutritional deficiencies such as
vitamin A and selenium, which could enhance tumor development (Seitz et al. 1998).
Genetic factors
There is abundant evidence reminding us that at all levels of consumption smoking
patterns correlate with alcohol consumption. This association is especially true for
higher consumption categories (Gulliver et al. 1995). A natural question pertains to the
reason for this association: Is there a genetic component? If so, how strong is the association,
and what gene(s) might be implicated?
Swan and associates in a multivariate analysis of Caucasian male twins identified
a genetic factor that explained the link between smoking, alcohol, and coffee use
(Swan et al. 1996). In a group of adolescent twins, Han et al. (1999) estimated the
heritable factor for tobacco and alcohol to be, respectively, 59 and 60% in males,
and 11 and 10% in females. The data could be explained by a common underlying
substance abuse factor. Koopmans and colleagues (1997) in a study of 1266 young
adult Dutch twins noted that alcohol and tobacco use was associated due to the same
genetic risk factors.
Since about 1990, evidence has been accumulating implicating a dopamine receptor
gene (DRD2) as a major factor in addictive disorders, including alcohol addiction and
smoking (Noble 1998; Noble 2000a, b). The prevalence of the A1 allele of the D2 dopamine receptor (DRD2) gene appears to be increased in both alcoholics, and
smokers. DRD2 may act as a reward or ‘pleasure’ gene; exposure to alcohol, tobacco, or
other addictive drugs, in conjunction with alterations in the DRD2 gene, might result
in an increase in brain dopamine levels, leading to enhanced feelings of reward and
satisfaction. These genetic defects could be important because they are potentially
associated with early age of onset of smoking or alcoholism (Comings et al. 1996; Kono
et al. 1997; Spitz et al. 1998).