Tobacco and Public Health - TCSC Indonesia

628
GENES, NICOTINE ADDICTION, SMOKING BEHAVIOUR, AND CANCER
studies conducted in 18 countries between 1995 and 2002 of candidate gene variation
and measured personality attributes. Many of the genetic variants in neurochemical
pathways hypothesized to be involved for personality associations are separately objects
of direct interest in nicotine addiction, e.g. serotonergic, dopaminergic, noradrenergic,
and GABAergic pathways. Again there is separate overlap with the neurochemical
pathways thought to be involved in susceptibility to mood disorder and generation of
mood state. The twin studies which have demonstrated strong evidence for heritable
components of smoking behaviour also suggest some overlaps in the genetic contribution
to smoking, personality, and mood, though classical twin studies cannot help to
pinpoint the particular contribution of individual genes (Sullivan and Kendler 1999).
The evidence suggests therefore that in examining the genetic contribution to smoking
behaviour we are looking for the cumulative effect of multiple genes exhibiting
relatively common allelic variations, which each confer only small variations in risk or
liability to the particular aspect of smoking behaviour. They may be differentially
important in different populations, they may exert their effect through a wide range
of mechanisms, they may contribute to different parts of the smoking process, and
the same overall level of risk or liability may arise from many different combinations
(i.e. heterogeneity of genotypic contributions) (Rutter and Plomin 1997).
Figure 35.2 illustrates some of the implications of different hypothetical models of
the population distribution of additive genotypic relative risk under different assumptions
of the number of genetic loci at which a small increase in risk is conferred by
possession of particular allelic variants, and the prevalence of these alleles in the
population. Integrating the notions of heritability and attributable risk is not yet easily
possible, but would serve communication about genotypic contribution to smoking
behaviour risk well if it were. As the figure shows the effects of the fixed small increases in
Percentage of population
40
30
20
10
0
10 genes, allelic prev. 25%
10 genes, allelic prev. 10%
5 genes, allelic prev. 25%
5 genes, allelic prev. 10%
2 4 6 8 10
Relative risk
Fig. 35.2 Hypothetical population distributions of additive genotypic relative risk. For each gene
locus: RR homozygous wildtype = 1; heterozygous variant = 1.22; homozygous variant = 1.5.