The 13th World Conference on Tobacco OR Health

The relationship between genes and cancer has been investigated but less attention has been paid to the major exposures that cause cancer, notably tobacco, alcohol and energy balance (obesity), each of which has a strong heritable component. Genetic factors influence smoking/nicotine dependence and heritability are substantial (46 to 84%). This does not lessen the importance of environmental factors, a key point since some have argued that genetics research should be limited to areas where the environmental contribution is unknown.

We investigate three 3 overlapping areas: first, genetic influences on smoking itself, with an increasing emphasis on diverse ‘phenotypes' that may share the genetic influence, i.e. smoking initiation, persistence, nicotine dependency, etc. A second area is the influence of genes on treatment outcomes. A third large area is the genetics of ‘harm', to understand which smokers are most vulnerable to major cancer and cardiovascular consequences.

Linkage analysis uses families and identifies chromosome regions shared by those with the trait, i.e. smoking. This approach has implicated various chromosome regions for further study but not unequivocally identified genes. Candidate gene studies nominate specific genes to investigate in large population-based samples and have focused on neurotransmitter genes, i.e. dopamine (DRD2), serotonin (SLC6A4). Metabolic genes such as those that influence the disposition of nicotine and nitrosamine carcinogens (i.e., CYP2A6) are prime candidates to influence both tobacco use and lung cancer.

New genomic technologies are revolutionizing these approaches and the prospects for ‘whole genome' studies and resulting ethical and social questions will be considered.