Environmental Risk Factors and Canine Malignant Lymphoma

描述（由申请人提供）： 在过去的30年里，美国人非霍奇金淋巴瘤（NHL）的发病率几乎翻了一番。流行病学研究已经评估了各种可能与NHL风险相关的因素，但结果不一致，无法解释发病率的急剧增加。几项人类流行病学研究表明，暴露于家庭环境烟草烟雾（ETS），草坪护理除草剂和杀虫剂（如跳蚤控制产品中所含的杀虫剂）可能会增加NHL的风险，但这些关系尚未得到很好的评价。伴侣动物的流行病学研究提供了一种补充手段，通过这种手段可以确定与动物和人类相关的癌症风险因素。由于犬恶性淋巴瘤（CML）已被确立为NHL的模型，家犬与人类主人共享其生活环境，因此环境暴露和CML的研究提供了一个独特的机会来评估可能与NHL相关的因素。拟议的病例对照研究将使用医院记录来识别CML病例和2个对照组的狗，一个由良性肿瘤狗组成，另一个由2000年至2005年期间在塔夫茨大学福斯特医院看到的非癌症慢性疾病狗组成。CML病例和对照组的所有者将在诊断前收到一份问卷，以评估家庭ETS、跳蚤控制产品的使用、草坪护理除草剂和其他因素。然后将使用多变量逻辑回归来评估环境暴露与CML风险之间的关系。此外，由于伴侣动物流行病学研究中使用的方法尚未得到很好的确立，因此拟议项目还将包括ETS暴露测量的验证研究，并评估主人特征是否与邮寄问卷的可能性相关。在两个月的时间内，1000只狗的主人将被要求完成一份测量人口统计学和环境因素的问卷，并提供他们的狗的尿样。将对大约130只狗的尿液样本进行可替宁水平分析，可替宁是尼古丁的代谢物，已被确定为ETS暴露的生物标志物，并将可替宁水平与问卷报告的家庭吸烟水平进行比较。一年后，将向所有参与者邮寄第二份调查问卷，并将比较答复者和非答复者的特点。然后，在使用一种新形式的敏感性分析计算相对风险时，将考虑任何差异，以更准确地估计环境暴露与CML风险之间的关联。由于狗和它们的主人在家庭中共享一个共同的环境，因此本研究的结果将与正在进行的确定可能增加人类NHL风险的因素的努力直接相关。

DESCRIPTION (provided by applicant): The incidence of human non-Hodgkin's lymphoma (NHL) in the US has nearly doubled over the previous 30 years. Epidemiologic research has evaluated a variety of factors potentially associated with risk of NHL but results have been inconsistent and cannot explain the dramatic increase in incidence. Several epidemiologic studies in humans have suggested that exposure to household environmental tobacco smoke (ETS), lawn care herbicides, and pesticides such as those contained in flea control products may plausibly increase risk of NHL, but these relationships have not been well evaluated. Epidemiologic studies of companion animals offer a complementary means by which to identify risk factors for cancers of relevance to both animals and humans. Because canine malignant lymphoma (CML) has been established as a model for NHL and domestic dogs share their living environment with their human owners, a study of environmental exposures and CML provides a unique opportunity to evaluate factors that may potentially relate to NHL. The proposed case-control study will use hospital records to identify cases of CML and 2 control groups of dogs, one consisting of dogs with benign tumors and one consisting of dog with non-cancer chronic diseases, seen at the Foster Hospital at Tufts University between 2000 and 2005. Owners of CML cases and controls will be sent a questionnaire to assess household ETS, use of flea control products, lawn care herbicides and other factors prior to diagnosis. Multivariate logistic regression will then be used to evaluate the relationship between environmental exposures and risk of CML. In addition, because the methods used in epidemiologic studies of companion animals are not well established, the proposed project will also include a validation study of ETS exposure measurement, and evaluate if owner characteristics are associated with likelihood of returning a mailed questionnaire. Owners of 1000 dogs presenting to Foster Hospital over a two-month period will be asked to complete a questionnaire measuring demographic and environmental factors, and to provide a urine sample from their dog. Urine samples from approximately 130 dogs will be assayed for level of cotinine, a metabolite of nicotine well established as a biologic marker for ETS exposure, and cotinine levels will be compared with level of household smoking reported by questionnaire. One year later, a second questionnaire will be mailed to all participants, and characteristics of respondent and non-respondent owners will be compared. Any differences will then be taken into consideration in the calculation of relative risks using a novel form of sensitivity analysis to produce more accurate estimates of the association between environmental exposures and risk of CML. Because dogs and their human owners share a common environment within the household, results from this study will have direct relevance to the on-going effort to identify factors that may increase risk of human NHL.