Developing Genetic Education for Smoking Cessation. Julia F. Houfek, PhD, APRN-CNS, BC Associate Professor UNMC College of Nursing

Transcription

1 Developing Genetic Education for Smoking Cessation Julia F. Houfek, PhD, APRN-CNS, BC Associate Professor UNMC College of Nursing

2 Research Team Members Lynne Buchanan, PhD, APRN-NP Pamela Jones, PhD, RN, MPH Gwendolyn M. Reiser, MS, CGC Victoria Graeve-Cunningham, BS Mamie Carlson, MPH Cecilia R. Barron, PhD, RN

3 Funding National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) R21 Grant (R21 DK ) RFA-DK : Translation of Common Disease Genetics into Clinical Applications

4 Smoking Prevalence: Adults Current smoking rates in the US (2009): Adults > 18 years: 20.6% Males: 23.5% Females: 17.9% Adults > 25 years & < H.S. diploma: 28.5% 45.3% (20.8 million) have quit for at least one day in the past year Little change in past 5 years Goal of Healthy People 2010: < 12% Sources: CDC (9/10/2010). MMWR, 59 (35), CDC (11/13/2009). MMWR, 58 (44),

5 Smoking Prevalence: Children & Adolescents Current tobacco use in US (2009): Middle School (grades 6-8): 8.2% for any tobacco and 5.2% for cigarette use High School (grades 9-12): 23.9% for any tobacco and 17.2% for cigarette use Little change from Goal of Healthy People 2010: < 16% for cigarettes and 21% for any tobacco use Source: CDC. (08/27/2010). MMWR, 59 (33),

6 Background & Significance Smoking is typically viewed as a behavior that can be changed with willpower. Viewed as a chronic disease Treatment is effective for only a portion of smokers Nicotine patch relapse long-term: 70-80% Bupropion: Most users do not achieve cessation Varenicline: 22% at 1 year, but significant SE for some smokers

7 Background & Significance Since the 1950s there has been evidence that smoking may be, in part, a heritable behavior Familial (Adoption and Twin) studies show a consistent relationship between smoking and heritability.

8 ADOPTION STUDIES Correlations between relatives for average reported cigarette consumption Biological Nonbiological Relationship Eysenck HJ, Correlation Coefficient Parent and offspring Identical (monozygotic) twins Fraternal (dizygotic) twins Siblings Adoptive parents and adoptive offspring 0.02 Adoptive siblings

9 Identical Twins 100% Genes in Common Non-identical Twins 50% Genes in Common Raised Together Raised Apart Raised Together Raised Apart Equally likely to smoke. Environment has less effect. No more difference in smoking. No more likely to smoke whether raised apart or together.

10 Heritability of Smoking from Familial Studies Smoking Initiation: genetic influences ~ 60 % shared environmental influences ~ 20% environment specific to individual ~ 20% Source: Sullivan, P.F. & Kendler, K.S. (1999). The genetic epidemiology of smoking. Nicotine & Tobacco Research, 1, S51-S57.

11 Heritability of Smoking from Familial Studies Smoking Maintenance: genetic influences ~ 70 % shared environmental influences: negligible environment specific to individual ~ 30% Genes that influence smoking maintenance may not be the same as for initiation Source: Sullivan, P.F. & Kendler, K.S. (1999). The genetic epidemiology of smoking. Nicotine & Tobacco Research, 1, S51-S57.

12 Heritability of Smoking: Genetic Influences Linkage studies and genome-wide association studies (GWAS) do not indicate there are genes with major effects for smoking Therefore, smoking is believed to be a complex trait influenced by: many genes, each with a small contribution environmental factors

13 Background & Significance Molecular genetic studies are focusing on identifying specific genes involved in smoking initiation, maintenance, and cessation: Candidate Gene Studies Genome Wide Association Studies (GWAS)

14 Smoking-Related Chromosomes Linkage Analyses and GWAS have identified the following chromosomes as having susceptibility loci for smokingrelated genes: 1, 2, 4, 5, 6, 9 10, 11, 14, 15 17, 18, 19, & 21.

15 Smoking-Related Genes Pharmacodyamics Dopamine Receptor activation DRD2, DRD4 Reuptake Dopamine Transporter SLC6A3 Metabolism Catechol-O-methyltransferase MAO A, MAO B Nicotinic acetylcholine receptor genes (CHRNA5/CHRNA3/ CHRNB4) Pharmacokinetics Nicotine Metabolism CYP2A6 CYP2B6 CYP2D6

16 Chromosome 11 DRD2 gene 5 Dopamine Receptor Gene 3 B 1 A 1 B 2 A 2 A1 allele associated with: Decreased number of receptors Younger age at initiation Fewer quit attempts

17 Genetic Studies Selected Findings: nach receptor genes Influence the structure and function of the nach proteins, 2-10 and β 2-4 Most research has focused on the 4β 2 subunit; varenicline is a partial agonist of this receptor Smokers with the TC genotype on the 4 subunit of the CHRNA4 were more likely to stay quit using nicotine nasal spray vs. patch Smokers with the GG vs. the A allele on the β 2 subunit of CHRNAB2 were more likely to quit with bupropion.

18 Chromosome 15 Nicotinic Acetylcholine Receptor genes: CHRNA3 CHRNA5 CHRNB4

19 Nicotinic Acetylcholine Receptor Genes Genetic variants in three subunit genes (CHRNA3, CHRNA5, and CHRNB4) associated with influencing smoking behaviors Nicotine levels Nicotine dependence Smoking quantity

20 Chromosome 19 CYP2A6 CYP1 CYP2 CYP3

21 Nicotine Metabolism Cancer Nicotine Breaks down Cotinine CYP2A6 Gene Carcinogens Activates Procarcinogens Excreted in Urine

22 Fast nicotine remover CYP1 Nicotine removed quickly More cigarettes needed Increased cancer risk CYP2 or 3 Nicotine stays longer Slow nicotine remover 10% of Population Fewer cigarettes needed Less dependency on cigarettes Less activation of procarcinogens Lower cancer risk

23 Background & Significance Great interest in using genetic information to develop better cessation treatments Goal of genetically-based smoking research: improve cessation outcomes by individualizing treatment based on a smokers genotypes Use of genotypes will require that smokers have an understanding of: genes and smoking benefits/drawbacks of having genetic information.

24

25 Challenges of Individualized Smoking Cessation Identify and teach smokers the knowledge and skills they need to fully participate in treatment. Use new genetically-based technologies in smoking cessation without promoting the perception that smoking is influenced solely by genetic or biological factors.

26 Purposes of Study Determine the effects of education about genetics and smoking on smoking-related schemas and behavior. Explore whether personality characteristics (trait negative affectivity and curiosity) and education moderate the effects of genetic education. Determine the feasibility of the study design.

27 Smoking is a Complex Trait Genes Environment Nicotine Dependence DRD2 Other Genes Nicotine Metabolism CYP2A6 Other Genes Peer Pressure Nicotine Availability Parental Smoking Stress Behavioral Traits Predisposition To Smoking

28 Aim 1 Moderating Variables Personality Traits: Negative Affectivity & Curiosity Educational Level Intervention Experimental Group: Education about Genetic Contributions to Smoking + Standard Smoking Cessation Attention Control Group: Education about Nutritional Guidelines + Standard Smoking Cessation Aim 2 Aim 1 Primary Outcomes Mental Representations: Genetic Contributions to Smoking: Knowledge Endorsement Attitudes Towards NRT Appraisals: Risk Perception for Genetic Predisposition for Smoking Self-Efficacy: Resisting Smoking & Achieving Abstinence Behaviors: Use of Cessation Strategies Abstinence: Point Prevalence & Continuous Interest in Genotyping Secondary Outcomes Mental Representations: Self-Schemas: Smoker & Abstainer Behaviors: Quit Attempts Nicotine Dependence Affective Responses: State Negative Affect & Intrusive/Avoidant Thoughts Figure 1. Genetic Education and Smoking Model

29 Methodology: Study Design Exploratory, experimental Convenience sampling Two-groups: Intervention and Control Longitudinal data collection at: Baseline After Intervention/Attention Control 3 & 6 months post-intervention

30 Baseline Assessment (Ti) Randomization Intervention Outcomes (Ta&b-T4) Background Variables: Sociodmographics Tobacco Use History Personality Traits: Negative Affectivity Curiosity Smoking-Related Mental Representations: Genetic Contributions to Smoking: Knowledge Endorsement Attitudes Towards NRT Self-Schemas: Smoker & Abstainer Smoking-Related Appraisals: Risk Perceptions for Genetic Predispositions Self-Efficacy: Resisting Smoking & Achieving Abstinence Smoking-Related Behaviors: Use of Cessation Strategies Randomization to Experimental and Attention Control Groups Stratification Variables: Gender (M/F); Number of Cigarettes Smoked/Day ( 20/> 20) Education about Genetic Contributions to Smoking Experimental Group SSC: Congnitive- Behavioral Smoking Cessation + NRT (TN) Attention Control Group Education about Nutritional Guidelines SSC: Cognitive- Behavioral Smoking Cessation + NRT (TN) Primary Outcomes Mental Representations: Genetic Contributions to Smoking: Knowledge Endorsement Attitudes Towards NRT Appraisals: Risk Perceptions for Genetic Predispositions Self-Efficacy: Resisting Smoking & Achieving Abstinence Behaviors: Use of Cessation Strategies Abstinence: Point Prevalence & Continuous Interest in Genotyping Secondary Outcomes Mental Representations: Self-Schemas: Smoker & Abstainer Behaviors: Quit Attempts Nicotine Dependence Affective Responses: State Negative Affect Intrusive/Avoidant Thoughts Figure 2. Schematic Diagram of the Experimental Design

31 Description of Intervention and Attention Control Groups Intervention Group Two 90-minute educational sessions: Basic Genetics Genetic contributions to smoking: DRD2 CYP2A6 Standard group smoking cessation over 5 weeks Attention Control Group Two 90-minute educational sessions: Healthy Eating/Current Nutritional Guidelines Nutrition Labeling & Safe Food Handling Standard group smoking cessation over 5 weeks

32 Selected Outcome Variables Knowledge of Genetic Contributions to Smoking (Knowledge Test) Genetic Predisposition Interest in Genotyping Smoker Self-Concept (Smoker & Abstainer Schemas) Smoking Cessation

33 Methodology: Instrumentation Knowledge Test: Genetics & Smoking 9 item investigator-developed test (T/F) Alpha (KR-20): r =.81 Smoker Self-Concept (Smoker & Abstainer Schemas): Alpha: r =.86 Risk Perceptions: Single-itemRating Scale: 1-10.

34 Instrumentation (con t) Interest in Genotyping: Investigatordeveloped single items on 5-pt. rating scale: Not at all (1) to Extremely (5) Abstinence: Point-prevalence and continuous: expired CO confirmed with salivary cotinine

35 Methodology: Data Analysis Descriptive Statistics T-tests Additional Analysis Repeated Measures ANOVA

36 Sample N = 72 (Intervention = 41; Control = 31) Gender: 37 Male; 35 Female Age: X = 44 years (SD = 12); Range: yrs Ethnicity: Caucasian = 63 (88%); African Americans = 6 (8%); Other = 3 (4%) Education: Most were H.S. graduates; very few with higher education Income: 67% < $40,000/yr

37 Sample (con t) Marital Status: 15 (21%) were married Employment: Full-time:31(44%); Other: 41 (56%) Perceived Health: Poor/Fair: 24(35%); Good: 31(46%); Very good/excellent: 12 (9%) Amount Smoked: X = 23 cigs/day (SD = 11 ) FTND Score: X = 6 (SD = 2)

38 Results: Knowledge Mean Scores at baseline were higher for the Intervention Group: t (df = 57) = 2.21, p =.03 Intervention: 4.78 (SD = 2.29) Control: 3.39 (SD = 2.42) Sample Questions: Different genes may affect whether or not a person begins smoking and whether s/he develops a regular smoking habit. Some genes may determine whether or not a smoker will develop lung cancer.

39 Results: Knowledge Change scores at the end of the Genetic and Nutritional Information Sessions also different: t (df = 57) = 3.17, p <.01 Intervention: 6.97 (SD = 1.82) Control: 3.70 (SD = 2.63)

40 Results: Interest in Genotyping Genetic Predisposition: t (df = 50) = 2.29, p <.03 Intervention: 4.16 (SD =.99) Control: 3.70 (SD = 2.63) Individualizing Cessation: t (df = 50) = 2.86, p <.01 Intervention: 4.47 (SD =.84) Control: 3.75 (SD = 1.11)

41 Results: Risk Perceptions Blood Test Predisposition: t (df = 63) = 1.55, p =.12 Intervention: 4.41 (SD =.96) Control: 4.00 (SD = 1.15) Blood Test Cessation: t (df = 63) = 1.57, p =.12 Intervention: 4.47 (SD =.90) Control: 4.07 (SD = 1.08)

42 Results: Interest in Genotyping Genotyping for Lung Cancer Predisposition: t (df = 63) = 1.91, p =.06 Intervention: 4.43 (SD = 1.01) Control: 3.89 (SD = 1.26) Payment: t (df = 63) = 1.46, p =.15 Intervention: 2.23 (SD = 1.31) Control: 1.83 (SD = 1.11) Most would pay $25-50

43 Results: Risk Perceptions Baseline: t (df = 60 ) = 1.46, p =.15 Intervention: 9.17 (SD = 2.89) Control: 8.04 (SD = 3.17) End of Genetic or Nutrition Information Sessions Change Scores: t (df = 60) = 3.09, p =.003 Intervention: (SD = 2.73) Control: 7.08 (SD = 2.92)

44 Results: Self-Concept & Abstinence Smoker Self-Concept: No significant differences in Smoker and Abstainer Self-Concept Scores at end of smoking cessation. Smoker Self-Concept: t (df = 24) = 0.70, p =.61 Abstainer Self-Concept: t (df = 25) = 0.74, p =.49 Abstinence: At the end of the Smoking Cessation Intervention 15 Intervention and 12 Control Participants were abstinent. t (df = 25) = 1.24, p =.23

45 Conclusions Intervention Group participants were able to assimilate and retain information from the genetic educational session (GES) The Intervention Group perceived that they were at higher risk for a genetic predisposition to smoking than the Attention Control Group.

46 Conclusions Intervention group participants had more interest in participating in Genotyping for genetic predisposition for smoking, individualizing cessation, and predisposion for lung cancer. The Intervention did not appear to influence Smoker/Abstainer Self-Concepts or Cessation rates.

47 Limitations Most data were self-report Difficulty in retaining the sample Difficulty in recruiting and retaining a diverse sample Many participants viewed the study as treatment rather than a research study

48 Future Analyses Look specifically at which questions in the Knowledge Test accounted for differences Examine if any of the items in the Self-Concept Scales changed over time and also whether scale scores were associated with Abstinence. Determine if risk perceptions are associated with Self-Concept Scores and Abstinence.

49 Thank you. Questions?