6.4 Influence of genetic factors on addiction
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Many influences contribute to the initiation of smoking, as discussed in Chapter 5. There is clear evidence that experimentation with tobacco and the progression to regular smoking are influenced by environmental factors; but it is also increasingly recognised that addiction may also be significantly influenced by physiological factors, which may have an underlying genetic variability.20-23 Twin studies have variously reported that heritability for smoking (that is to say, the proportion in the variance in smoking that is attributable to genetic factors) ranges from about 50%-80%, which is in keeping with heritability estimates for alcoholism, asthma, and hypertension.22 Inherited factors influencing initiation and dependence are likely to overlap, to some degree, but there is evidence that independent genetic influences may mediate each stage of tobacco use.24-26
Research on the genetic variability of addiction, as distinct from initiation or experimentation, suggests that 60% to 75%20, 25, 26 of the variation may be due to individual genetic factors.
Although a limited number of genes have so far been implicated in addiction, it is likely that multiple genes are involved, each having only a small effect.21, 27 The range of studies of various 'candidate' genes to date has resulted in inconsistent findings, probably due to the technical difficulties in analysing so complex a behaviour as smoking in which genes and environment both play a part.23 Plausible pathways by which individual genetic differences might influence susceptibility to addiction include variations in the number and sensitivity of nicotine receptors, the speed and efficiency of nicotine metabolism, and variations in physiological and behavioural responses to nicotine exposure.21, 22, 27 Recent research has found that inherited variation within the human CYP2A6 gene influences the rate at which the body metabolises nicotine,28 which in turn may affect an individual's level of tobacco consumption.29
While research into the genetics of addiction may eventually yield benefits of more targeted and enhanced pharmacological assistance with cessation, the role of environmental factors contributing to long term smoking rates is not to be underestimated, given that up to 50% of the variance in smoking appears to be due to environmental factors.30 According to Hall et al, 'Improved understanding of the genetics of smoking are not likely to affect public health tobacco control policies. It is much simpler, cheaper and more efficient to discourage the whole population from smoking tobacco than it is to attempt to make smoking safer by identifying those at highest risk of nicotine addiction or smoking-related disease.'23 p 123
Further issues relating to genetic predisposition to tobacco-caused disease are discussed in Chapter 3, Section 3.22. The possible contribution of genetic research to advances in smoking cessation is discussed in Chapter 7, Section 7.7.7.6.
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