Alcohol Consumption and Risk of Rheumatoid Arthritis in Women

描述（由申请人提供）：类风湿性关节炎（RA）是一种慢性、破坏性、使人衰弱的关节炎，主要影响女性，其病因尚不完全清楚。它被认为是一种多因素疾病，是遗传和环境因素共同作用的结果。流行病学研究已经提供了令人信服的数据，说明了强烈的环境风险因素，包括吸烟、使用外源性激素和女性生殖因素。最近，人类遗传学的进展已经确定了22个与类风湿性关节炎相关的风险等位基因。根据以往的病例对照研究，作为一个重要的生活方式因素，饮酒与RA风险降低有关。然而，大多数回顾性确定酒精暴露的病例对照研究受到回忆偏倚的限制。唯一一项关于酒精和类风湿性关节炎的前瞻性队列研究受限于少数病例，并且使用了一次性自我报告的酒精测量，这可能会导致暴露状态的错误分类偏差。因此，需要更大样本量和更准确的酒精测量的控制良好的前瞻性队列研究。护士健康研究（NHS）是世界上对影响妇女健康的因素进行的规模最大、历时最长的调查之一。从1976年开始，1989年扩大，238,000名专职护士参与者提供的信息为研究罕见疾病（如风湿性关节炎）提供了独特的机会。基于现有的NHS数据，我们提出以下具体目标：1)在控制年龄、种族、吸烟、生殖因素和外源性激素使用后，研究饮酒与女性RA发展之间的关系。根据美国风湿病学会的分类标准，所有RA事件病例均由2名委员会认证的风湿病学家确诊。从1980年国民健康保险制度1和1989年国民健康保险制度2开始，到非病例调查问卷的最后一个周期和病例RA发病前，在半定量食物频率问卷中反复评估酒精消费量。我们将使用重复测量的累积平均酒精消费量，而不是一次性测量，以最好地代表长期酒精消费量。2)通过在NHS队列中嵌套的匹配病例对照亚样本（500例RA事件病例，500例匹配对照），研究22个已确定的RA遗传风险等位基因与饮酒之间的相互作用。这些创新的研究将促进对类风湿性关节炎病因的理解，为类风湿性关节炎的预防策略提供额外的信息，并提供潜在的公共卫生影响，如何改变生活方式因素可能影响患类风湿性关节炎的风险。

DESCRIPTION (provided by applicant): The etiology of rheumatoid arthritis (RA), a chronic, destructive, debilitating arthritis that disproportionately affects women, remains incompletely understood. It is considered to be a multifactorial disease, resulting from the interaction of both genetic and environmental factors. Epidemiologic research has produced convincing data for strong environmental risk factors, including cigarette smoking, exogenous hormone use and female reproductive factors. Recently, advances in human genetics have identified 22 risk alleles associated with RA. Alcohol use, as an important lifestyle factor, has been associated with reduced risk of RA based on previous case-control studies. However, most case-control studies which ascertained alcohol exposure retrospectively were limited by the recall bias. The only prospective cohort study on alcohol and RA was limited by small number of cases, and used a one time self-reported alcohol measure that may induce misclassification bias of exposure status. Thus well-controlled prospective cohort studies with larger sample size and more accurate alcohol measures are needed. The Nurses' Health Studies (NHS) are among the largest and longest running investigations of factors that influence women's health in the World. Started in 1976 and expanded in 1989, the information provided by the 238,000 dedicated nurse-participants has provided the unique opportunity to study rare diseases such as RA. We propose the following specific aims based on existing NHS data: 1) To investigate the association between alcohol consumption and the development of RA in women after controlling for age, race, cigarette smoking, reproductive factors and exogenous hormone use using entire NHS cohorts. All RA incident cases were confirmed by 2 board-certified rheumatologists according to American College of Rheumatology classification criteria. Alcohol consumption was assessed repeatedly within a semi-quantitative food frequency questionnaire started from 1980 in NHS 1 and 1989 in NHS II to the last cycle of the questionnaire for non-cases and before RA onset for cases. We will use cumulative average alcohol consumption across repeated measures instead of one-time measure to best represent long-term alcohol consumption. 2) To investigate interactions between 22 identified genetic risk alleles for RA and alcohol consumption using a matched case-control subsample with genotyping (500 incident RA cases, 500 matched controls) nested in NHS cohorts. These innovative studies will advance understanding of RA etiology and furnish additional information for RA prevention strategies, and provide potential public health implications how a modifiable lifestyle factor may influence the risk of developing RA. PUBLIC HEALTH RELEVANCE: Alcohol use as an important lifestyle factor may be associated with decreased risk of RA. However, definitive data supporting this association from well-controlled prospective studies are lacking. Findings from this large cohort study will clarify the possible protective effect of alcohol use on risk of RA in women and furnish additional information for RA prevention strategies.