Impact of a Gene Test for Susceptibility to Lung Cancer in Smokers

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.

Inclusion criteria

• Aged 20-70 years
• Smoking more than 10 cigarettes daily

Exclusion criteria

• Aged under 20 years or over 70 years
• Smoking less than 10 cigarettes daily
• History of major depression and other psychiatric conditions, dementias and serious or terminal illness (cancers etc.).
• Patients on warfarin would be excluded due to interactions between warfarin and varenicline as varenicline will be used as the modern treatment of choice for smoking cessation.

Patients who did not wish to have a genetic test would be referred to the practice nurse for smoking cessation.