Christopher Taylor's story tells it all. Here is a man who smoked but wanted to quit. Like many smokers, Taylor was interested in better understanding his own risk profile for lung cancer through the gene-based Respiragene ™test. On the basis of his test result, and with his new determination, he has been successfully smoke free for 4 weeks, much longer than any previous attempts.

Taylor, who is 45 and had smoked for 25 years, told the New York Times that of course he already knew cigarettes were dangerous. But he thought, "It's not going to happen to me." Then came the Respiragene™ test. "To actually take a test that says you are genetically prone to this, then there's no excuse," he said.

Some smokers are particularly susceptible to the damaging effects of cigarette smoke due to genetic factors.  That genetic predisposition, combined with smoking, means an increased risk of lung cancer.  Respiragene™ combines well-established non-genetic and genetic factors to produce a clinically meaningful risk measure that for smokers like Taylor may be just the trigger they need to quit smoking, or to seek the help that will significantly improve their chances of success.

New approaches to old problems should attract informed debate, but some comments quoted in the NYT article about our Respiragene™ lung cancer risk test are inaccurate -- perhaps because some commentators have not kept pace with the latest research in this fast-moving area.

 

• The article quotes geneticist David Goldstein as saying genetic variants used in the test do not meet current standards of evidence. That is not correct. Twelve of 20 genetic markers used have also been validated by leading scientists from all over the world in various studies involving thousands of patients. Several of the risk markers identified by our team relate to susceptibility to chronic obstructive pulmonary disease (COPD or smoker's lung). COPD is the most important risk factor for developing lung cancer in smokers but until now has been overlooked by most other genetic researchers of lung cancer. The COPD risk markers we include have also been robustly reviewed in various scientific publications.
• There is no commonly accepted standard for evidence covering discoveries and conclusions in the rapidly emerging fields of biomarker discovery and translational medicine. Peer-reviewed publications, of which we have several, remain the most reliable benchmark. 
• The test includes risk variables such as age, family history and the presence of COPD; all have been independently associated with increased lung cancer risk. It is well accepted that risk tests are stronger overall when several risk variables are reliably combined. We've shown this is the case with multiple genetic and non-genetic factors, as published in peer-reviewed articles including one in October's Postgraduate Medical Journal.
  
• The Respiragene™ test includes several genetic markers that have emerged from the large genome-wide studies that are the current gold standard for identifying individual susceptibility markers. However Dr Goldstein's comments appear to reflect his previously reported views ("A dissenting voice as genome is sifted to fight disease", NYT September 15, 2008) that such work has yielded only very limited progress in personalized medicine. Many more eminent scientists and researchers strongly disagree. Dr Goldstein's comment that the principal determinant of lung cancer risk is "how much and whether you smoke" misses the point of this test, and is inaccurate when considering the actual risk level differences among smokers, which is the objective of our test. Of course smoking is a critical risk factor -- about 90% of lung cancers are diagnosed in current or former smokers. But Dr Goldstein's statement ignores extensive scientific literature that shows that lung cancer has a genetic basis; and that it affects only some smokers, regardless of how much they smoked.
• The risk tool referred to by Dr Peter Bach, which includes only age, sex and smoking history, was developed before the role of COPD in lung cancer susceptibility was fully appreciated and before a series of genetic markers for lung cancer had been identified in multiple studies. For many smokers, Dr Bach's reported advice, "you should stop smoking", while correct, is neither enlightening nor empowering. Respiragene™, as we are seeing, can be both.
• The studies referred to by Dr Sanderson were based on a single genetic marker then known that identified only a small increase in lung cancer risk for carriers. Yet according to published studies, even this information had a positive impact on would-be quitters. These studies found, as we have, that there is no evidence that genetic testing reduces the individual's desire to quit. Our more advanced test, unlike most single marker assays, provides a significantly more powerful risk indicator than previously available. That distinguishes it from many tests for a variety of indications now on the market.
• The article reviews the tobacco industry's potential research interest in this area and the fact that Auckland University and I discussed research funding with British American Tobacco a decade ago. However, we chose not to accept any funding then, or at any time. I want to make absolutely clear that no group in the tobacco industry has sponsored any part of our research or development.

Smoking cessation is among the most cost-effective preventive health interventions available to doctors today. We agree that the cost-effective use of genetic testing to help spur changes in smoking behavior remains to be confirmed.  Christopher Taylor, whose use of the test prompted him to quit his habit, is a participant in an ongoing pilot trial where 35% of the individuals who took the Respiragene™ test stopped smoking after getting their results. The survey, to be expanded, also shows that over 90% of test takers found it to be useful and said they would recommend it to a family member or friends who smoked. A larger trial in the United States, overseen by smoking cessation thought leaders at prestigious institutions and hospitals, is in the works. Engaging smokers with valid, actionable data about their personal risk informs everything we do.

Prepared by Dr Robert Young, MD, PhD

Chief Scientific Officer - Synergenz BioScience Ltd.

Associate Professor of Medicine and Molecular Medicine

School of Biological Sciences, University of Auckland

Links to the original articles can be found here and here.

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