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Will Nicotine Genetics and a Nicotine Vaccine Prevent Cigarette Smoking and Smoking-Related Diseases?

  • Wayne D Hall
  • Published: September 27, 2005
  • DOI: 10.1371/journal.pmed.0020266

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Genetic Research on Nicotine Dependence Will Facilitate the Public Health

Posted by plosmedicine on 30 Mar 2009 at 23:46 GMT

Author: Joe Cubells
Position: Associate Professor of Human Genetics and
Institution: Emory University School of Medicine
E-mail: jcubells@genetics.emory.edu]
Submitted Date: September 28, 2005
Published Date: September 28, 2005
This comment was originally posted as a “Reader Response” on the publication date indicated above. All Reader Responses are now available as comments.

W.D. Hall's cogent essay on the folly of attempting to use predictive genetic testing in public-health measures to prevent nicotine dependence is a valuable contribution. Indeed, his arguments against predictive testing can easily be applied to virtually any complex genetic disorder. It is certainly important that we in the medical-research community continue to offer such articulate education to clinicians, the lay press, and society at large.

There is a danger, however, that his arguments will be seized upon by those who oppose supporting research on the genetics of nicotine dependence and other addictions, to the detriment of the public health. For example, Merikangas and Risch [1] have already proposed that addictions and several other complex diseases be deprived of Federal research support in favor of other complex disorders, arguing, 'the expensive and laborious tools of molecular genetics [should] be prioritized to those diseases ... that cannot now be treated or prevented with environmental changes [such as] type 1 diabetes, multiple sclerosis, autism and schizophrenia. In contrast, gene hunting for disorders that appear to be highly amenable to environmental modification, such as type 2 diabetes, AIDS, alcohol dependence and nicotine dependence, would have lower priority [for Federal research support], even though genes may be involved in their etiology.' Those arguments were picked up by right-wing commentators and trumpeted in high-profile lay outlets such as the New York Times. For example, Humphreys and Satel [2] (the latter a resident scholar at the American Enterprise Institute) cite Merikangas and Risch when they conclude, 'Some gene research just isn't worth the money ... [because] major cuts in drug- and alcohol-related harm depend not on genes but on choices by policy makers and individual citizens.' Thus the myth that addictive behavior is simply a matter of 'choice' is made to appear to have solid science behind it, when in my view, the only real rationale for opposing genetic research on disorders related to smoking, drinking, over-eating, homosexual sex and other 'sinful' behavior derives from the same strain of religious moralism underlying creationism and intelligent design.

Such arguments miss the most important rationale for genetic research on addictions and other environmentally-influenced complex disorders. These conditions deserve continued vigorous support from the NIH and other sources because genetic research is a powerful tool for pointing us toward new treatments based on improved understanding of the biology of the disorder. Nicotine dependence is an important case in point, because current treatments, which consist of psychosocial interventions, and medication therapies such as nicotine replacement and buproprion, are in a word, ineffective: Relapse rates following smoking cessation with those strategies, while slightly better than no intervention, usually exceed 80% at one-year follow-up [3].

Genetic research, by providing suggestive evidence for associations to the genes encoding the gamma-amino butyric acid (GABA) B receptor subunit 2 [4], or the cannabinoid-1 receptor [5] [6], has already helped to light the way toward potentially more effective interventions for millions who struggle to quit smoking, but repeatedly fail. While predictive testing of risk for nicotine dependence based on those genetic findings is quite useless, it remains to be ascertained whether pharmacogenetic profiling will be useful for identifying those most likely to benefit from specific medications (or for that matter, psychosocial interventions), or who would be at risk for harmful side-effects from an otherwise effective drug. While the potential for such profiling has been hyped in the popular press just as predictive testing has been, we have only to recall the lives saved by understanding the genetic basis of variation in thiopurine methyltransferase activity, in the context of thiopurine chemotherapy for acute lymphoblastic leukemia [7], to convince ourselves of the importance of studying the genetic basis of all common complex diseases, whether partially amenable to environmental prevention or not.

References
1. Merikangas, K.R. and N. Risch, Genomic priorities and public health. Science, 2003. 302(5645): p. 599-601.
2. Humphreys K, S. Satel, Some gene research just isn't worth the money, in New York Times. 2005. p. F5.
3. USDHHS, Reducing Tobacco Use. A Report of the Surgeon General, Atlanta, GA: US Office on Smoking and Health. 2000.
4. Beuten, J., et al., Single- and multilocus allelic variants within the GABA(B) receptor subunit 2 (GABAB2) gene are significantly associated with nicotine dependence. Am J Hum Genet, 2005. 76(5): p. 859-64.
5. Uhl, G.R., et al., Polysubstance abuse-vulnerability genes: genome scans for association, using 1,004 subjects and 1,494 single-nucleotide polymorphisms. Am J Hum Genet, 2001. 69(6): p. 1290-300.
6. Zhang, P.W., et al., Human cannabinoid receptor 1: 5' exons, candidate regulatory regions, polymorphisms, haplotypes and association with polysubstance abuse. Mol Psychiatry, 2004. 9(10): p. 916-31.
7. Weinshilboum, R. and L. Wang, Pharmacogenomics: bench to bedside. Nat Rev Drug Discov, 2004. 3(9): p. 739-48.

Competing interests declared: I am currently supported by a career development award from the National Institute on Drug Abuse, and collaborate in several ongoing basic-research projects in addiction genetics. The opinions expressed here are the solely the author??s.