Spitz M R, Shi H, Yang F, Hudmon K S, Jiang H, Chamberlain R M, Amos C I, Wan Y, Cinciripini P, Hong W K, Wu X
Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
J Natl Cancer Inst. 1998 Mar 4;90(5):358-63. doi: 10.1093/jnci/90.5.358.
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 (A1 and A2) and the TaqIB allele (B1 and B2) of the D2 dopamine receptor gene in 157 lung cancer case patients and 126 control subjects were determined to assess whether individuals homozygous or heterozygous for the less common A1 and B1 alleles are more vulnerable to nicotine addiction.
Case and control subjects were accrued from an ongoing epidemiologic study. Blood samples were 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.
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 not observed among those with A1 genotypes. Statistically significant correlations between the presence of the A1 and B1 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 A1 and B1) and having attempted to quit smoking fewer times (statistically significant for only A1).
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.
多巴胺受体基因的结构和表达存在个体差异，这会影响多巴胺的可用性，可能是吸烟易感性差异的遗传基础。在本研究中，测定了157例肺癌病例患者和126名对照受试者中D2多巴胺受体基因的TaqIA等位基因（A1和A2）和TaqIB等位基因（B1和B2）的多态性患病率，以评估A1和B1这两种较罕见等位基因的纯合子或杂合子个体是否更容易对尼古丁成瘾。
病例和对照受试者来自一项正在进行的流行病学研究。采集他们的血样并进行分子遗传学分析。对受试者进行访谈以获取相关信息。对当前和既往吸烟者进行问卷调查，以量化他们对尼古丁的成瘾程度。
在病例患者中，曾经吸烟者的B1B2基因型组合似乎比从不吸烟者更普遍（30.3%对13.3%；双侧P = 0.233），在对照受试者中也是如此（30.9%对0%；双侧P = 0.02）；A1基因型者之间未观察到统计学上的显著差异。观察到A1和B1等位基因存在之间有统计学上的显著相关性（病例受试者r = 0.73，对照受试者r = 0.76；双侧P<0.001）。基因型较罕见的个体报告开始吸烟时年龄要小得多（A1和B1均具有统计学显著性），且尝试戒烟的次数较少（仅A1具有统计学显著性）。
D2多巴胺受体基因的变异等位基因可能在决定尼古丁成瘾方面发挥作用，尽管高危基因型与尼古丁成瘾指标之间的关联并不完全一致。
