Environmental Risk Factors and Canine Malignant Lymphoma

描述(由申请人提供)： 在美国，人类非霍奇金淋巴瘤(NHL)的发病率在过去30年中几乎翻了一番。流行病学研究已经评估了各种可能与非霍奇金淋巴瘤风险相关的因素，但结果并不一致，无法解释发病率的急剧上升。在人类中的几项流行病学研究表明，暴露于家庭环境烟草烟雾(ETS)、草坪护理除草剂和杀虫剂(如蚤类控制产品中所含的杀虫剂)可能会增加患非霍奇金淋巴瘤的风险，但这些关系尚未得到很好的评估。对同伴动物的流行病学研究为确定与动物和人类相关的癌症风险因素提供了一种补充手段。由于犬恶性淋巴瘤(CML)已被建立为NHL的模型，并且家犬与其主人共享它们的生活环境，因此对环境暴露和CML的研究为评估可能与NHL潜在相关的因素提供了独特的机会。拟议的病例对照研究将使用医院记录来确定慢性粒细胞白血病病例和两组对照狗，一组由患有良性肿瘤的狗组成，另一组由患有非癌症慢性病的狗组成，这两组狗是2000年至2005年在塔夫茨大学福斯特医院看到的。慢性粒细胞白血病病例和对照的所有者将在诊断前收到一份问卷，以评估家庭ETS、跳蚤防治产品的使用、草坪护理除草剂和其他因素。然后将使用多变量Logistic回归来评估环境暴露与慢性粒细胞白血病风险之间的关系。此外，由于同伴动物流行病学研究中使用的方法还不成熟，拟议的项目还将包括ETS暴露测量的验证研究，并评估所有者特征是否与退回邮寄问卷的可能性有关。在两个月的时间里，1000只狗的主人将被要求完成一份调查问卷，衡量人口统计和环境因素，并提供他们的狗的尿样。大约130只狗的尿样将被检测可替宁水平，可替宁是尼古丁的代谢物，被公认为暴露于ETS的生物标志，可替宁水平将与问卷报告的家庭吸烟水平进行比较。一年后，第二份问卷将邮寄给所有参与者，并将比较受访者和非受访者业主的特征。然后，在使用一种新的敏感性分析形式计算相对风险时，将考虑到任何差异，以更准确地估计环境暴露与慢性粒细胞白血病风险之间的联系。由于狗和它们的主人在家庭中共享一个共同的环境，这项研究的结果将与正在进行的识别可能增加人类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.