Tobacco and Public Health - TCSC Indonesia

634
GENES, NICOTINE ADDICTION, SMOKING BEHAVIOUR, AND CANCER
DAT genotype. However there was some evidence of effect in those who possessed
allelic variants of the cytochrome enzyme CYP2B6 (which may play a part in metabolizing
nicotine and is responsible for metabolizing bupropion to other active compounds).
The subject of genetic contribution to smoking behaviour is clearly still in its
infancy, and the promises and pitfalls of unravelling the contribution are similar to
those involved in the hunt for many other ‘disease’ genes. However the subject is finally
on the agenda in the search for how to reduce the toll tobacco takes.
Some possible implications of improving our understanding of the genetic contribution
to smoking behaviour might be speculated on:
◆ How will the tobacco industry react if genetic susceptibility is demonstrated? Will it
try to argue that responsibility for nicotine addiction lies with the individual
because of their genetic make-up?
◆ How will the pharmaceutical industry, who make the effective smoking cessation
aids respond to the notion that not all smokers should be considered part of the
market for their drug if another might suit them better?
◆ How will professionals respond to the notion of individualizing therapy, based on
treatments preferred for smokers with a particular genotype?
◆ How will smokers react to the notion that their wish to smoke stems partly from
their genetic make up, having become tobacco dependent in the first place?
Investigations in these areas will be needed.
We now turn to a brief overview of the state of understanding of how a smoker’s
genotype may alter their risk of developing cancer. More detailed consideration of
genotype and specific cancer risk amongst active smokers is provided in the cancer
specific chapters elsewhere in this book.
Smoking-related cancer
Cigarette smoking has an aetiological link with several types of cancer, predominantly
solid tumours of the lung, larynx, pharynx, oesophagus, bladder, kidney, and pancreas
but also including myeloid leukemia. Although a large number of cancer deaths are
caused by smoking (in 1999, 22% of all cancer deaths were of lung cancer), only a proportion
of smokers ultimately develop lung cancer (Mattson et al. 1987). The precise
reasons for this remain unclear, but the discrepancy most likely results from the combination
of variation in carcinogen exposure and genetic susceptibility. (Zang and
Wynder) The Table 35.1 earlier in the chapter indicates that lung, and the other smoking-related
cancers, have heritability estimates that, whilst not as great as for some
other cancers, are nonetheless substantial. Current studies focus on genetic susceptibilities
to lung cancer in particular, and how they modify the effects of tobacco smoke
carcinogens. Studies on bladder cancer have also been performed but other cancers are
less well studied in this area.