Abstract A86: Psychosocial and genetic determinants of cigarette experimentation in Mexican heritage youth
Authors: Wilkinson Anna V. , Etzel Carol J. , D'Amelio Anthony , Prokhorov Alexander V. , Pu Xia , Wu Xifeng , Bondy Melissa L. , Spitz Margaret R. 
Published: May 2012

Mexican American youth have the highest rates of smoking experimentation. We have previously confirmed several psychosocial factors including cognitive susceptibility to smoking, outcome expectations, risk taking tendencies, family influence and demographic characteristics, as risk factors for experimentation in these youth. In this study, we evaluated the incremental value of adding select variants of two candidate genes in the dopamine pathway implicated in the smoking phenotype. Participants were Mexican origin youth recruited from a large population-based cohort study in Houston, TX, who provided prospective data on cigarette experimentation yearly for five years. Psychosocial data on family influence, risk taking tendencies and outcome expectations were elicited at two time points-baseline and final follow-up. At baseline, all participants provided buccal samples, from which DNA was extracted and genotyped for 27 genetic variants in the dopamine receptor DRD2, and Dopamine Transporter (DAT) genes. Of the 1002 youth in the current analysis, 52% were girls, 66% were born in the US, average age at baseline was 11.8 (SD=0.8) years, 78% reported being highly acculturated, and 22% reported being new experimenters (i.e. first experimented with cigarettes only subsequent to the baseline survey). Two SNPs were associated with experimentation: rs10052016 (p&lt;0.004) and rs1826909 (p&lt;0.001). We completed multivariable analyses to predict new experimentation based on previously identified risk factors described above and incorporated the genotype data into the model. After controlling for the established risk factors, we found that participants with 3 or 4 risk alleles were 1.72 (95% CI: 1.09–2.72) times more likely to have experimented since baseline compared to participants with 0 or 1 risk allele. Introducing the genes to the model did not attenuate the ORs of the established psychosocial risk factors. Having determined that the interaction between the risk alleles and susceptibility was significant, we stratified the sample by susceptibility status and reran the multivariable analyses. Among non-susceptible youth (N=778), the genes were not predictive of experimentation but the psychosocial factors were. However, among susceptible youth (N=224) besides standard risk factors for new experimentation (being a boy, age 13 at baseline, and living with a smoker), there was a significant gene dosage effect (p-trend&lt;0.01). Compared with carriers of 0 or 1 risk allele, those having two risk alleles exhibited an OR of 3.58 (95% CI: 1.45–8.84) and for carriers of 3 or 4 risk alleles the OR was 3.99 (95% CI: 1.57–9.91). These results suggest that genetic variations in DRD2 and DAT genes interact with a cognitive predisposition toward smoking to significantly increase the chances of experimenting with cigarettes among Mexican origin youth. We plan to evaluate a more comprehensive panel of genes, and to replicate these findings among youth of other ethnic backgrounds.

Citation Information: Cancer Prev Res 2010;3(1 Suppl):A86.