The 13th World Conference on Tobacco OR Health

The ability to study genetic traits and disease risk has progressed over 20 years, where small laboratories can conducting studies of 10,000 subjects and more. The genetic susceptibility for smoking-related disease begins with behavioral traits (e.g., personalities more likely to initiate smoking and to become addicted and less likely to quit). The number of cigarettes smoked/day, and inhalation is governed by nicotine metabolism and maintaining specific nicotine blood levels. Genetics also codes for harmful effects relating to carcinogen metabolism, DNA repair, cell cycle control and apoptosis. Many candidate genes have been studied, and even more remain. It is problematic how to choose which genes to study, and high-throughput methodologies increase false positive (chance) findings. There is a focus on studying low penetrant genetic traits, but there is no evidence that this approach will be more fruitful than identifying moderate penetrant traits. The study of func tional genetic variants is preferred. However, most are not known, and so haplotyping methods have come into vogue as a screening method. But, the lack of a priori hypotheses yields its own challenges, and also increases the chances of false positives and population effects. To date, phenotyping methods that represent complex genetic traits remain among the best for characterizing susceptibilities, but the technical feasibility is usually beyond all but a handful of laboratories. The choice of studying SNPs, haplotypes and phenotypes will be discussed, and corroborative evidence supporting the roles for candidate genes and phenotypes will be presented.