a genetic link to smoking addiction and cessation


As an alumni of the University of Toronto, I am often sent their newsletters updating me on the latest research offerings.  This month they report on a new study led by Professor Rachel Tyndale at U of T, which looks at how the use of a biomarker can aid in smoking cessation.  The study researchers will report to the smoker whether he/she has the gene variant that can break down nicotine slowly or quickly, which can affect addiction and therefore chances of quitting.  In this trial, they will randomize these individuals to different treatment conditions (placebo, nicotine patch, or varenicline), but it is envisioned that knowing the status of this biomarker in an individual will help to tailor future cessation treatments.

I have two comments on this.  It has been hypothesized that Asians (Chinese-origin, Japanese-origin, among others) have slower nicotine metabolism due to a genetic variation in the CYP2A6 gene (the same gene of interest in the U of T study).  Consequently, Asians may need less nicotine to become addicted, explain their lower risks of lung cancer and possible require different doses of nicotine replacement drugs when trying to quit (Benowitz et al 2002, Derby et al 2008).  It’s not clear if this new trial led by Professor Tyndale will recruit smokers from ethnic minorities, but it would certainly be interesting to further test this hypothesis on a large scale.

I am also reminded of a study by Colleen M. McBride and colleagues (2002) which used a similar method of incorporating feedback of a different biomarker, GST3 gene (GSTM1), for an African-American population.   The GST3 gene comes in two variants – one that can help detoxify some of the carcinogens in cigarettes and one that can not.  The trial compared two groups of smokers, those that received feedback on their own ability to detoxify carcinogens, and those that did not received this feedback.  All participants received the same quit-smoking guidance.  They found that at 6 months there was a difference in cessation rates between the two groups (19% versus 10%, respectively; P < 0.006),  but that the differences disappeared at 12 months.  This study can offer some sobering insights into the world of cessation research – knowledge of increased risk may not always have the desired long-term impact.


Benowitz et al.  Slower Metabolism and Reduced Intake of Nicotine From Cigarette Smoking in Chinese-Americans.  J Natl Cancer Inst 2002; 94(2):108-15 (PDF)

Derby et al. Nicotine Metabolism in Three Ethnic/Racial Groups with Different Risks of Lung Cancer.  Cancer Epidemiol Biomarkers Prev 2008; 17(12):3526-35 (PDF)

McBride et al (2002) Incorporating genetic susceptibility feedback into a smoking cessation progrm for African-American smokers with low income. Cancer Epidemiol Biomarkers Prev 2002; 11:521-528 (PDF)

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