Diet, gene-diet interactions and risk of Parkinson's

申请人描述(申请人提供)：候选人陈红雷，医学博士，具有两年以上帕金森氏病(PD)研究经验，现为哈佛大学公共卫生学院副研究员。陈博士的研究兴趣包括散发性帕金森病的环境和遗传病因以及其他神经退行性疾病，他计划在这一领域发展独立的学术生涯。在这项K08建议中，陈博士在癌症预防研究-11营养队列(CPS-IIN)中提出了一项关于饮食与散发性帕金森病风险的大型前瞻性调查，并在卫生专业人员随访研究(HPFS)和护士健康研究(NHS)中提出了一项关于帕金森病基因多态和基因-饮食交互作用的大型嵌套病例对照研究。在CPS-IIn中，他将前瞻性地研究162,408名美国男性和女性中PD与饮食摄入量的关系，重点是叶酸、咖啡、饮食抗氧化剂、脂肪、酒精和乳制品。CPS-IIN正在确认发生的帕金森病病例，他们预计将记录1992年至2001年期间诊断的550例明确和可能的帕金森病病例。在HPFS和NHS队列中，他将评估帕金森病风险与Nat2、CYP1A2、ADH2、ADH3、ADH4和MTHFR常见基因多态的相关性。他还将首次探索帕金森病病因中的基因-饮食相互作用，包括NAT2、CYP1A2和咖啡因摄入量；ADH2、ADH3、ADH4和酒精摄入量；以及MTHFR和叶酸摄入量。截至2000年，他们记录了567例明确和可能的帕金森病病例，其中454例提供了血液或面颊细胞用于基因分析。在这项拟议的嵌套病例对照研究中，将为每个年龄和性别匹配的PD病例选择两个对照。这项建议中包括的所有三个队列都是公认的大型预期队列，具有全面的(基线和最新的)和有效的饮食评估以及严格的结果确定。此外，这项研究的范围使其成为迄今为止规模最大的调查之一。已完成或即将完成的数据收集将进一步使这项研究更具成本效益。因此，K08基金将同时实现两个重要目标：帮助陈博士培养技能，成为神经系统疾病流行病学的独立研究员，并加深我们对饮食、基因和帕金森病病因之间复杂相互关系的理解。

DESCRIPTION (provided by applicant): The candidate, Honglei Chen, M.D., Ph.D., has more than two years research experience in Parkinson's disease (PD) and is currently a Research Associate at Harvard School of Public Health. Dr. Chen's research interest includes the environmental and genetic etiology of sporadic PD and that of other neurodegenerative diseases, and he plans to develop an independent academic career in this area. In this K08 proposal, Dr. Chen proposes a large prospective investigation of diet and risk of sporadic PD in the Cancer Prevention Study-ll Nutrition Cohort (CPS-IIn) and a large nested case-control study of PD with genetic polymorphisms and gene-diet interactions in the Health Professionals Follow-up Study (HPFS) and the Nurses' Health Study (NHS). In the CPS-IIn, he will prospectively examine among 162,408 US men and women associations of PD with dietary intakes, focusing on folate, coffee, dietary antioxidants, fat, alcohol, and dairy products. Confirmation of incident PD cases in CPS-IIn is ongoing and they expect to document 550 definite and probable PD cases diagnosed between 1992 and 2001. In the HPFS and NHS cohorts, he will evaluate the associations of PD risk with common polymorphisms of NAT2, CYP1A2, ADH2, ADH3, ADH4, and MTHFR. He also will, for the first time, explore gene-diet interactions in PD etiology, including NAT2, CYP1A2 and caffeine intake; ADH2, ADH3, ADH4, and alcohol intake; and MTHFR and folate intake. Through the year of 2000, they have documented 567 definite and probable PD cases and 454 of them provided either blood or cheek cells for genetic analysis. In this proposed nested case-control study, two controls will be selected for each PD case matching on age and gender. All three cohorts included in this proposal are well-established large prospective cohorts with comprehensive (baseline and updated) and validated dietary assessments and rigorous outcome ascertainments. Moreover, the scope of this study makes it one of the largest investigations to date. The completed or nearly completed data collection will further make this study most cost-effective. Therefore, this K08 grant will simultaneously accomplish two important goals: helping Dr. Chen develop the skills to become an independent researcher in the epidemiology of neurological diseases and furthering our understanding of the complex interrelationships among diet, genes and PD etiology.