Personalized Medicine and Tobacco-Related Health Disparities: Is There a Role for Genetics?

We thank Dr. David for his interest in our work. Dr David laments the absence of genetically-tailored smoking cessation trials. Yet there have been at least 3 studies that would seem to qualify as such [1-3]. These studies have failed to show a benefit of genetic data in enhancing cessation rates. It is always possible that a future study will bear fruit, particularly if new data suggest potential effects not yet fully investigated, such as the opportunity for genetics to direct choice of cessation treatment. We also caution that a robust comparative effectiveness approach be taken, to ensure that any test of genetic approaches is compared to current, proven, smoking cessation methods including counseling on lung age, bans, etc. We do not believe that modeling exercises, particularly those in which the conclusions vary dramatically depending on assumptions, can provide sufficiently compelling evidence on these questions.

We also appreciate the comments of Drs. Carpenter and Strange but must express our strong disagreement with the statement that "genetic testing is the cornerstone of personalized medicine." Rather, we argue that personalized medicine is characterized by careful attention to the individual characteristics and circumstances of each patient, the vast majority of which are ascertained without genetic testing. Furthermore, while genetic testing may be "the most rapidly expanding segment of the molecular diagnostics market worldwide" there is little evidence that this expansion is proportionate to evidence for its usefulness [4]. We agree that our challenge is to “direct new science, provide evidence on its impact, and guide policy for its use". An important component of this effort is critical thinking about which uses of new technology are most likely to provide net benefit, and this was one intention of our paper.

In this context, the claim that "willingness to undergo genetic testing is a self-selected choice" is likely simplistic. Rather, the choice to undergo testing is likely influenced by physician recommendations, funders’ willingness to pay, and media coverage. The need for rigorous evaluation, to ensure that physicians and funders have the evidence and critical review they need, is all the more important given the media attention to genetics.

We agree that genetics should, in concept, be complementary rather than an alternative to existing modes of treatment – a tool to assist in the delivery of personalized medicine in some instances. We argue that there are likely to be limited opportunities for benefit within the smoking cessation context. More importantly, we call for this question to be addressed with rigorous research, to assure that any use of genetic testing to assist smoking cessation is based on a clear demonstration of cost-effectiveness compared to alternative approaches. The best opportunities appear likely to come from the application of pharmacogenomics, but even here, as Carpenter and Strange wisely advocate, caution is indicated.

1. Carpenter MJ, Strange C, Jones Y, Dickson MR, Carter C, Moseley MA, Gilbert GE. Does genetic testing result in behavioral health change? Changes in smoking behavior following testing for Alpha-1 Antitrypsin Deficiency. Ann Behav Med. 2007;33(1):22-28.

2. McBride CM, Bepler G, Lipkus IM, et al. Incorporating genetic susceptibility feedback into a smoking cessation program for African- American smokers with low income. Cancer Epidemiol Biomarkers Prev. 2002;11(6):521–528.

3. Hishida A, Terazawa T, Mamiya T, et al. Efficacy of genotype notification to Japanese smokers on smoking cessation—an intervention study at workplace. Cancer Epidemiol. 2010;34(1):96–100.

4. Evans JP, Meslin EM, Marteau TM, Caulfield T. Genomics. Deflating the genomic bubble. Science. 2011 Feb 18;331(6019):861-2.

Competing interests:   None declared

We endorse Carlsten et al’s analysis of the major limitations in using genomic information to reduce social disparities in smoking prevalence1. We would stress a major limitation in the use of genetic information to tailor smoking cessation assistance to smokers, namely, that smoking risk and likelihood of cessation is likely to involve many risk alleles of small effect which makes it difficult to predict differential responses to smoking cessation interventions2. Combining multiple risk alleles into genetic testing may improve prediction3 but we have shown that a predictive genetic test based on 5 risk alleles was a poorer predictive tool than simple family history information4. The inclusion of more predictive alleles of moderate effect size in such a genetic test only modestly improves prediction. The substantial expense in identifying those genetically at the highest risk of relapse is unlikely to be justified by the small increment in successful cessation.

The use of genetic risk information could also be counter-productive, if geneticising tobacco addiction reduces quitting self-efficacy among disadvantaged smokers2. We agree with Carlsten et al1 that more promising options for reducing the social disparity in smoking rates and tobacco- related disease are population health strategies, such as taxation, smoking bans, subsidised cessation aids, and more controversially, tobacco harm reduction options5, that are tailored to the social needs of disadvantaged smokers.

Coral Gartner, NHMRC Research Fellow and Wayne Hall, NHMRC Australia Fellow, The University of Queensland Centre for Clinical Research.

1. Carlsten C, Halperin A, Crouch J, Burke W. Personalized Medicine and Tobacco-Related Health Disparities: Is There a Role for Genetics? Annals of Family Medicine. 2011;9 (4):366-371.

2. Hall WD, Gartner CE, Carter A. The genetics of nicotine addiction liability: ethical and social policy implications. Addiction. 2008;103 (3):350–359.

3. Yang QH, Khoury MJ, Botto L, Friedman JM, Flanders WD. Improving the prediction of complex diseases by testing for multiple disease- susceptibility genes. American Journal of Human Genetics. 2003; 72 (3): 636–649.

4. Gartner CE, Barendregt JJ, Hall WD. Multiple genetic tests for susceptibility to smoking do not outperform simple family history. Addiction. 2009; 104 (1): 118–126.

5. Gartner CE, Hall WD, Vos T, Bertram MY, Wallace AL, Lim SS. Assessment of Swedish snus for tobacco harm reduction: an epidemiological modelling study. The Lancet. 2007; 369 (9578):2010-4.

Competing interests:   None declared

Carlsten and colleagues (1) provide well-stated cautionary advice on the potential role of genetics in the treatment of tobacco dependence. They argue that access to proven therapy is the most effective public health strategy to lower smoking prevalence, particularly among disadvantaged smokers. While correct, this truism minimizes the impact of the genetic revolution. Genetic testing is the cornerstone of personalized medicine (2) and is the most rapidly expanding segment of the molecular diagnostics market worldwide (3). Our challenge is to direct new science, provide evidence on its impact, and guide policy for its use.

Genetics should not be viewed as an alternative to existing treatments, but rather a complement to them. Genetic information will unlikely supplant existing strategies, either at the individual or community level. However, many smokers either will not engage in or do not respond to existing treatments (4). We need new options. Willingness to undergo genetic testing is a self-selected choice. Smokers will either seek genetic testing or get information from their trusted healthcare provider, but a scenario where all smokers are advised to undergo genetic testing as a part of standard care is hard to envision.

Finally, we are reminded of old maxim: absence of evidence is not evidence of absence. As investigators on one study that examined the impact of genetic testing on downstream smoking behavior (5), we, like others, found that knowledge of genetic status prompted beneficial change (increase in quit attempts). The benefit on actual cessation was less clear: while there was a three-fold increase in abstinence among smokers at higher vs. lower genetic risk, this did not reach statistical significance, largely due to limited sample size. These findings are generally consistent with other research in this area. We are aware of no study that has shown a decrease in cessation as a function of genetic testing.

We agree with Carlsten et al. that more and stronger effort should be made to promote access to the cessation tools we know work. Anyone anticipating a genetic panacea requires corrected vision, but we are more sanguine about its potential role in the future. We believe that genetic testing may someday augment existing treatment and identify familial risks before smoking begins. Genetic testing may someday help us select from the menu of effective cessation medications by identifying populations with enhanced efficacy to medications. We should keep all tools at our disposal in this important task.

Matthew J. Carpenter, PhD and Charlie Strange, MD, Medical University of South Carolina

1. Carlsten C, Halperin A, Crouch J, Burke W. Personalized medicine and tobacco-related health disparities: Is there a role for genetics? Ann Fam Med. 2011;9(4):366-371.
2. Collins F. Has the revolution arrived? Nature. 2010;464:674- 675.
3. http://www.prweb.com/releases/genetic_testing/molecular_diagnostics/prweb8055136.htm
4. Fiore MC, Jaen CR, Baker TB, Bailey WC, Benowitz NL, Curry SJ, et al. Treating tobacco use and dependence: 2008 Update. Clinical Practice Guideline. Rockville, MD: US Public Health Service; 2008.
5. Carpenter MJ, Strange C, Jones Y, Dickson MR, Carter C, Moseley MA, Gilbert GE. Does genetic testing result in behavioral health change? Changes in smoking behavior following testing for Alpha-1 Antitrypsin Deficiency. Ann Behav Med. 2007;33(1):22-28.

Competing interests:   None declared