Case-control study of the D2 dopamine receptor gene and smoking status in lung cancer patients

Background: Interindividual differences in the structure and expression of the dopamine receptor genes affect dopamine availability and may be the genetic basis for variation in vulnerability to tobacco smoking, In this study, prevalences of polymorphisms in the TaqIA allele (A(1) and A(2)) and the TaqIB allele (B-1 and B-2) of the D-2 dopamine receptor gene in 157 long cancer case patients and 126 control subjects were determined to assess whether individuals homozygous or heterozygous for the less common A(1) and B-1 alleles are more vulnerable to nicotine addiction, Methods: Case and central subjects were accrued from an ongoing epidemiologic study, Blood samples cr;ere collected from them and subjected to molecular genetic analyses, Subjects were interviewed to obtain relevant information. Current and former smokers were administered a questionnaire to quantify their addiction to nicotine, Results: The combined B1B2 genotypes appeared to be more prevalent in ever smokers than in never smokers among case patients (30.3% versus 13.3%; two-sided P = .233) and among control subjects (30.9% and 0%; two-sided P = .02); statistically significant differences were nor observed among those with A(1) genotypes. Statistically significant correlations between the presence of the A(1) and B-1 alleles were observed (r = .73 for case subjects and r = .76 for control subjects; two-sided P < .001), Individuals with rarer genotypes reported having been substantially younger at the time of smoking initiation (statistically significant for both A(1) and B-1) and having attempted to quit smoking fewer times (statistically significant fur only A(1)), Conclusion: Variant alleles of the D2 dopamine receptor gene may play a role in determining nicotine addiction, although the associations between the at-risk genotypes and measures of nicotine addiction were not entirely consistent.