Biobehavioral Model of Smoking By Russians with Cancer

自2000年以来，Fox Chase癌症中心与俄罗斯Blokhin癌症中心合作，促进俄罗斯肿瘤学家的培训，并促进国际研究，以降低癌症发病率和死亡率。为此，这些中心一直在研究与治疗癌症患者尼古丁成瘾有关的问题。这项提案将通过关注尼古丁成瘾的生物行为方面来扩展这项研究。影响多巴胺释放和可用性的遗传多态性可能是戒烟能力极端变异的原因。该领域的大多数研究评估了多巴胺受体基因DRD 2和DRD 4的多态性以及多巴胺转运蛋白基因SLC 6A 3的多态性。最近还研究了新的基因，如大麻素CB 1受体。这一领域的复制受到以下因素的阻碍：1）种族混合，这可能导致人群分层偏倚; 2）使用粗略和不同的吸烟表型评估; 3）依赖横截面数据; 4）使用小样本，这妨碍了对基因-环境和基因-基因相互作用的评估。在本研究中，我们将考虑这些方法学问题：1）评估新诊断癌症患者样本中DRD 2、DRD 4、SLC 6A 3基因型和CB 1受体的患病率，并将这些基因与吸烟状态相关联; 2）检查这些基因是否预测戒烟以及在多大程度上预测戒烟; 3）评估这些基因之间的相互作用以预测吸烟状态;（4）探讨抑郁症状与这些基因在预测吸烟状况方面的相互作用。如果尼古丁成瘾的基因研究要导致个性化的吸烟治疗和新的预防方法，那么就需要考虑这些方法学问题的研究。这些研究还解决了俄罗斯的一个重大公共卫生问题，促进了Blokhin癌症中心专业知识的发展，并更广泛地推进了尼古丁成瘾治疗领域。

DESCRIPTION (provided by applicant): Since 2000, Fox Chase Cancer Center has partnered with the Blokhin Cancer Center in Russia to foster the training of Russian oncologists and to facilitate international research to reduce cancer morbidity and mortality. To this end, the centers have been studying issues related to treating nicotine addiction among cancer patients. This proposal will extend this research by focusing on the biobehavioral aspects of nicotine addiction. Genetic polymorphisms that affect the release and availability of dopamine may account for the extreme variability in the ability to quit smoking. Most research in this area has assessed polymorphisms on dopamine receptor genes DRD2 and DRD4 and polymorphisms in the dopamine transporter gene SLC6A3. New genes have also been recently examined such as the cannabinoid CB1 receptor. Replication in this area has been hampered by: 1) ethnic admixture, which can cause population stratification bias; 2) use of crude and varying assessments of smoking phenotypes; 3) a reliance on cross-sectional data; and 4) use of small samples, which prevent the assessment of gene-environment and gene-gene interactions. In this study, we will consider these methodological issues and: 1) Assess the prevalence of DRD2, DRD4, SLC6A3 genotypes, and the CB1 receptor in a sample of newly diagnosed cancer patients and correlate these genes with smoking status; 2) Examine whether or not and to what degree these genes predict cessation longitudinally; 3) Evaluate the interaction among these genes in terms of predicting smoking status; and 4) Explore the interaction between depressive symptoms and these genes in terms of predicting smoking status. If genetic studies of nicotine addiction are to lead to personalized treatments for smoking and novel methods for prevention, studies that consider these methodological issues are needed. Such research also addresses a major public health problem in Russia, facilitates the development of expertise at the Blokhin Cancer Center, and advances the field of nicotine addiction treatment more broadly.