Abstract PL04-02: Genetics and health care disparities caused by smoking.

Abstract

Abstract In the U.S., racial/ethnic differences are seen in smoking behavior and related disease risk. Compared to smokers of European ancestry, African Americans smoke fewer cigarettes per day, but take in more nicotine and smoke per cigarette and appear to be more highly dependent. Asians also smoke fewer cigarettes per day put appear to be less dependent than smokers of European ancestry. Lung cancer incidence normalized by cigarettes smoked per day is higher for African Americans and lower in Asians compared to smokers of European Ancestry. Genetic variations in two genes are most strongly associated with smoking behavior and lung cancer risks, and these are found in different frequencies across races. CYP2A6 is the enzyme that is primarily responsible for nicotine metabolism, and is also involved in the bioactivation of the tobacco-specific nitrosamine and lung carcinogen NNK. There are many reduced function variants of the CYP2A6 gene, and these are more frequent in Asians and African Americans compared to those of European ancestry. The presence of reduced function CYP2A6 variants is associated with smoking fewer cigarettes per day and with lower dependence, the latter evidenced by more successful quitting. Among smokers of European ancestry and Asians, reduced function CYP2A6 variants are associated with lower lung cancer risk. However, for unknown reasons, despite having a higher prevalence of reduced function CYP2A6 alleles, African Americans have higher risks for lung cancer. Genes in the nicotine receptor subunit gene cluster CHRNA5-A3-B4 have been associated with lung cancer risk in a number of studies, and have also been associated with nicotine intake and with risk of chronic obstructive lung disease and peripheral arterial disease. It is that believed that the α5 nicotinic receptor subunit influences sensitivity to nicotine; and reduced function of the subunit results in a greater level of nicotine and smoke intake, and therefore a higher level of dependence. Relatively little is known about the effects of this gene cluster on smoking behavior or cancer risk in African Americans or Asians. Among European Ancestry smokers, the CYP2A6 gene and CHRNA5-A3-B4 gene cluster are additively associated with cigarette consumption, nicotine dependence and lung cancer risk. Genetic risk factors are important determinants of racial differences in smoking behavior and lung cancer risk, but explain only a relatively small amount of variation in risk among smokers. Citation Format: Neal L. Benowitz. Genetics and health care disparities caused by smoking. [abstract]. In: Proceedings of the Fifth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2012 Oct 27-30; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(10 Suppl):Abstract nr PL04-02.