Impact of a Gene Test for Susceptibility to Lung Cancer in Smokers
Condition: Smoking Cessation
MeSH terms: Lung Neoplasms
Study type: Interventional

Summary: 
      Professor RP Young (Associate Professor of Medicine and Molecular Medicine, School of
      Biological Sciences, University of Auckland) and his team have developed a reliable genetic
      test "Respiragene" based on 20 single nucleotide polymorphisms that can be used (together
      with details of personal and family history) to calculate a smoker's lifetime risk of
      developing lung cancer. The expectation is that whatever the score (estimated lifetime risk
      will vary from 5% to 50%) the result will counter "optimism bias" of the smoker and encourage
      smoking cessation and this assumption is supported by previous research on similar tests and
      smoking cessation. The investigators plan to recruit two groups of subjects for smoking
      cessation but only one group will have the Respiragene test. Eight weekly smoking cessation
      sessions will be carried out at a Surrey primary care medical centre and will follow the
      usual format for National Health Service smoking cessation clinics using Champix
      (varenicline), counselling and the carbon monoxide breath meter but with added: evaluation
      questionnaires, fagerstrom nicotine addiction score, salivary cotinine (metabolite of
      nicotine) test. The main outcome measures will be estimation of smoking cessation at 4 weeks
      and six months after the completion of the seven smoking cessation sessions. Successful
      smoking cessation has to be confirmed by negative salivary cotinine at 4 weeks and six months
      and questionnaires will be used to estimate the influence of the Respiragene test compared
      with standard procedures such as counselling and the carbon monoxide breath readings.
    

Detailed description: 
      Despite the 5-10% probability of lung cancer in smokers, 50% do not believe they are at
      significantly increased risk Despite this, over 80% of smokers would like to know their
      personal risk of lung cancer. RP Young, a clinician at University of Auckland, has show a
      three way link between biomarkers for COPD, a set of 20 single nucleotide polymorphisms
      (SNPs) and lung cancer. He has demonstrated a strong correlation between a risk score
      (derived from family history of cancer, the 20 SNPs & clinical COPD) and the development of
      lung cancers whereas healthy smokers (who had not developed lung cancer) matched for age,
      gender and lifetime smoking habits had a relatively low risk score (n=446 lung cancer
      subjects, 484 healthy current smokers. The odds ratio for lung cancer risk varied from
      0.2-3.2 depending on the genetic risk (p<0.001). The Auckland lung cancer risk score has a
      90% sensitivity for a score of >4. The validity of 20 SNP gene test has also been confirmed
      in populations in Barcelona, Spain and Liverpool, United Kingdom. The test has been given the
      trade name "Respiragene".

      Small uncontrolled trials of use of Respiragene in smoking cessation clinics in New Zealand
      and USA show an improvement in smoking cessation at six months after a Respiragene
      intervention with quit rates of 30-35%. The trial hypothesis is that smokers who have the
      Respiragene test and a full explanation of their risk score will have a better quit rate at 4
      weeks and at six months (after completion of their eight weekly smoking cessation clinic
      sessions) than controls. Smoking cessation at the six month follow up will bw confirmed by
      testing for salivary cotinine. Based on data from Young's small trial, we also hypothesise
      that this uplift of quit rate will be seen for subjects with both high risk scores and
      average risk scores (there is no low risk category for smokers). These hypotheses are the
      basis of the primary end points.

      The investigators will also be administering the same questionnaire to each subject and
      control twice, at 4 weeks and six months (after the smoking cessation course) that is
      primarily designed to evaluate the impact of the Respiragene test in relation to other
      influences:

        -  other components of the smoking cessation clinic sessions (salivary cotinine testing,
           carbon monoxide breath analyser, general clinic help and advice, clinic fact sheets)

        -  general environmental factors (cost of cigarettes, family pressure, work regulations,
           doctor's advice)

      The results will be analysed using Statistical Package for the Social Sciences (SPSS)
      Statistics 17.0 computer programme.
    

Intervention name(s): Respiragene test and risk score
Intervention type(s): Genetic
Intervention description(s): This 12 gene test used with other data (family history, age and spirometry result) to calculate lifetime risk of lung cancer in smokers who do not quit smoking. This intervention is expected to be a motivator to quit.
Other intervention name(s): Respiragene test, Lab 21, Cambridge
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Prevention
Keywords: Nicotine addiction; Behaviour; Gene test; Lung cancer; Lifetime risk of lung cancer in smokers