Genetic Analysis of Polymorphisms in Dopamine Receptor and Transporter Genes for Association with Smoking among Cancer Patients

Abstract

Background: Smoking among Russian cancer patients may be related to variations in the DRD2/ANKK1 (Taq1), DRD4 (exon III VNTR), and SLC6A3 genes. Methods: Seven hundred fifty patients provided smoking history and DNA. Results: Current smokers were more likely to be DRD2 A2 allele carriers versus nonsmokers (former/never smokers; 69 vs. 56%; OR = 1.69; 95% CI 1.13–2.53, p = 0.01) and former smokers (69 vs. 59%; OR = 1.54; 95% CI 0.97–2.46, p = 0.07). Ever smokers (current/former smokers) were more likely to be DRD2 A2 allele carriers versus never smokers (65 vs. 55%; OR = 1.50; 95% CI 1.00–2.27, p = 0.05). The risk of current smoking among DRD2 A2 allele carriers was present if the DRD4 short allele was also present (OR = 1.76; 95% CI 1.12–2.78, p = 0.02), and the risk of ever smoking among DRD2 A2 allele carriers was present if the DRD4 short allele was also present (OR = 1.62; 95% CI 1.02–2.55, p = 0.04). DRD2 A2 allele carriers had a shorter period of previous abstinence versus DRD2 A1 carriers (p = 0.02). Effects were not statistically significant when controlling for multiple comparisons. Conclusions: The DRD2 A2 allele may increase the risk of smoking among cancer patients, convergent with studies using non-Western samples. However, additional replication is needed.

Meta-analysis reveals significant association of 3′-UTR VNTR in SLC6A3 with smoking cessation in Caucasian populations

“…However, this association was not replicated by follow-up studies. 22 , 23 , 25 , 32 – 34 Although negative or totally opposite results have been published, the general results indicate that smokers who carry one or more 9-repeat alleles are more likely to quit smoking than smokers who carry no such allele.…”

“…Because the data used in the David study 38 consisted of the data from two other independent studies, 39 , 40 we excluded the study with the pooled sample and only included the two original studies for our current meta-analysis. Thus, a total of 12 smoking cessation-related studies were included in this meta-analysis, which consisted of four cross-sectional studies, 19 , 22 , 23 , 25 , 41 one no-treatment longitudinal study, 20 and six treatment longitudinal studies. 32 – 34 , 38 , 41 , 42 In the cross-sectional studies, surveyed participants were classified as either former smokers or current smokers.…”

“…Both Sabol et al 19 and Vandenbergh et al 23 defined current smokers as those who not only had smoked at least 100 cigarettes in their lifetimes but who also smoked either daily or occasionally at the time of the survey and former smokers as those who had smoked at least 100 cigarettes but not smoked immediately before the survey. In two other cross-sectional studies, 22 , 25 participants were classified as current or former smokers according to their answers to the following questions: “Are you currently smoking?” and “Have you ever smoked regularly?” Furthermore, the classification method of the non-treatment longitudinal study 20 depended on the responses of participants who were smokers at baseline to the questions one year later, and biochemical verification as well.…”

“…A 40-base-pair variable number tandem repeat (VNTR) in the 3′ un-translated region (UTR) of the SLC6A3 gene, consisting of 3–16 repeats, is frequently investigated in smoking cessation studies. 19 , 20 , 22 – 25 In all reported studies in various ethnic populations, the common alleles of 3′-UTR VNTR polymorphism are the 10-repeat and 9-repeat. Other rare alleles are excluded in certain studies because of their low frequency.…”

Can Intermittent Theta Burst Stimulation as Add-On to Psychotherapy Improve Nicotine Abstinence? Results from a Pilot Study

“…For a detailed description of the molecular and neural processes involved in nicotine addiction, withdrawal symptoms and craving, the reader is referred to the available literature [e.g. [14,15,16,17,18,19]]. More specifically, studies indicate a positive modulation of addiction-related behaviors, such as decreased craving or consumption following rTMS of the right or left PFC [cocaine: [20], alcohol: [21], nicotine: [22,23]] or transcranial direct current stimulation (tDCS) of the bilateral PFC [alcohol: [24], nicotine: [25]].…”