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Genetic Expression and Nicotine Withdrawal

CYP2A6 gene graphic

Whereas there is strong evidence that cigarette smokers metabolize nicotine at dramatically different rates, and that the rate of metabolism is largely governed by specific genes, it is not clear how the expression of these genes translates into smoking behavior and the experience of nicotine withdrawal syndrome. Conventional wisdom suggests those smokers who suffer more frequent withdrawal symptoms sooner after smoking a cigarette would be more likely to have difficulty quitting. Unfortunately, there is a paucity of data that explores the role genetic differences in the speed of nicotine metabolism may play in sustaining smoking behavior in the time between one cigarette and the next. We are currently looking at how differences in nicotine metabolism may be related to psychological and physiological symptoms of nicotine withdrawal during an acute period of nicotine abstinence. Specifically, we are looking at how variation in the expression of a gene responsible for eliminating nicotine from the body interacts with the experience of subjective nicotine craving, withdrawal symptoms and negative emotional states during a four-hour period of nicotine withdrawal. Moreover, we are hoping to contribute to the understanding of the early phases of nicotine withdrawal by mapping the temporal sequence of both physiological and psychological signs and symptoms of withdrawal over a short period of time.

Nicotine Addiction

Time to first cigarette (TTFC) is a strong predictor of nicotine uptake as measured by cotinine, the major metabolite of nicotine measured in blood or urine. A dose-dependent relationship has been observed between earlier TTFC and cotinine levels. Even after adjusting for cigarettes smoked per day, adult smokers who smoke within five minutes after waking had double the levels of cotinine than smokers who waited for an hour or more after waking. Our research has shown that TTFC is also a predictor of nicotine uptake in adolescent smokers – even among those teens who do not smoke every day. Additionally, we have shown that TTFC is associated with higher levels of a nicotine-specific carcinogen (NNAL), regardless of the number of cigarettes smoked. We have also shown that among adolescent smokers trying to quit, TTFC was a predictor of cessation outcomes: those teens who smoke sooner after waking up in the morning are significantly less likely to be successful quitters. We are currently working on projects that may help us further understand nicotine addiction as measured by TTFC and specifically how TTFC increases risk.

Cancer patient cessation

The lack of an empirically-validated smoking cessation program specifically designed to meet the needs of cancer survivors represents a critical problem for the comprehensive treatment and long-term survival of a vulnerable population. Each year, hundreds of thousands of smokers receive a cancer diagnosis. Although many of these smokers quit following their diagnoses, as many as 60% may not quit or soon relapse back to regular smoking. Continued smoking following a cancer diagnosis is related to a number of deleterious outcomes including tumor recurrence, development of secondary tumors, decreased quality of life and lower survival rates. Additionally, smoking may reduce the effectiveness of cancer therapy and may increase treatment-related side effects. A cessation program tailored to the specific issues and needs of cancer patients is likely to result in higher rates of cessation among survivors and improved long-term outcomes; unfortunately, only a limited number of interventions have been developed and evaluated specifically to assist this population. Moreover, few of these interventions have demonstrated compelling treatment effects. Our long-term goal is to improve cancer treatment outcomes and cancer patient quality of life through the reduction or elimination of a key behavioral risk-factor: continued cigarette smoking. We are currently collecting data from patients and their family members to garner a comprehensive understanding of the factors relating to ongoing smoking in this population, the barriers to successful cessation attempts, and how family members and the cancer treatment team may help or hinder cessation.