Risk of Non-Hodgkin's Lymphoma in Relation to Tricyclic Antidepressant Use

描述（由申请人提供）：在美国和大多数西方化国家，非霍奇金淋巴瘤（NHL）的发病率在过去40年中几乎翻了一番，疾病报告和分类的变化以及已知风险因素的患病率并不能解释这种增加的全部原因。两项先前的研究提供了三环类抗抑郁药（TCAs）的使用与NHL发生之间相关性的证据，但他们无法研究NHL亚型之间的相关性，已知NHL亚型在病因上是多样的。为了响应美国国立卫生研究院宣布在癌症流行病学的小额赠款，我们建议进行一项病例对照研究，NHL的成员组健康（GH），一个大型的综合医疗服务系统在西部华盛顿州。病例将包括1980-2009年期间诊断为NHL的所有GH成员，年龄为25岁，诊断时已成为GH成员2年，并且符合排除标准。将从GH成员的定义人群中选择对照，因此它们应代表引起病例的人群。他们将与年龄（5岁年龄组）、性别、病例诊断日期（参考日期）和成员年限的病例按8：1进行匹配。将使用30年自动化药房数据库确定TCA的使用，该数据库包含在GH分发的每种处方的详细数据，在整个研究期间一致和前瞻性地记录，因此在参考日期之前，病例和对照组也是如此。我们将测试是否：（1）以前的TCA用户是在NHL的风险增加，和（2）是否协会不同类型的NHL。这些数据将允许有效评估NHL的风险与TCA使用的持续时间、剂量、剂量和类型有关，包括总体和特定类型的NHL。该研究具有典型的病例对照设计的优点，因为它在成本和时间轴方面都是有效的，同时也避免了病例对照研究中经常发现的许多偏倚。使用前瞻性收集的自动化数据可防止回忆偏倚和信息偏倚，使用GH入组者的定义人群可确保对照代表NHL风险人群。 公共卫生相关性：在过去的四十年里，美国非霍奇金淋巴瘤（NHL）的发病率几乎翻了一番，使其成为男性和女性中第六常见的癌症，这种增长并不能完全由已知因素解释。以前的研究表明，三环类抗抑郁药（TCA）使用者患NHL的风险增加，但他们没有检查与TCA使用相关的特定NHL亚型的风险。由于TCA继续被广泛使用，并且由于这类常见癌症亚型的病因异质性，因此评估TCA使用者的NHL发病率是一项重要任务。

DESCRIPTION (provided by applicant): The incidence of non-Hodgkin's lymphoma (NHL) has nearly doubled over the past four decades in the US and most westernized countries, and changes in disease reporting and classification and in the prevalence of known risk factors do not account for the entirety of this increase. Two prior studies provided evidence for an association between use of tricyclic antidepressants (TCAs) and the occurrence of NHLs, but they were unable to investigate associations within NHL subtypes, which are known to be etiologically diverse. In response to the National Institutes of Health announcement for small grants in cancer epidemiology, we propose to conduct a case-control study of NHL among members of Group Health (GH), a large integrated healthcare delivery system in western Washington State. Cases will include all GH members with a diagnosis of NHL between 1980-2009, who were e25 years old and had been GH members for e2 years at diagnosis, and who meet the exclusion criteria. Controls will be selected from the defined population of GH members, thus they should be representative of the population that gave rise to cases. They will be matched 8:1 with cases on age (5-year age groups), sex, date of case's diagnosis (the reference date), and length of membership. TCA use will be ascertained using a 30-year automated pharmacy database which contains detailed data on every prescription dispensed at GH, recorded consistently and prospectively throughout the study period and thus prior to reference date and similarly for cases and controls. We will test whether: (1) prior TCA users are at an increased risk of NHL, and (2) whether the association varies by type of NHL. These data will permit a valid assessment of the risk of NHL in relation to the duration, dose, regency, and type of TCA use, both overall and for specific types of NHL. The proposed study has the advantages typical of the case-control design, as it is efficient in terms of both costs and timeline, while also avoiding many of the biases often found in case-control studies. The use of prospectively collected automated data prevents recall bias and information bias, and use of the defined population of GH enrollees ensures that controls are representative of the population at risk of NHL. PUBLIC HEALTH RELEVANCE: Rates of non-Hodgkin's lymphoma (NHL) have nearly doubled over the past four decades in the US, making it the sixth most common cancer in both men and women, and this increase is not entirely explained by known factors. Previous studies suggest that tricyclic antidepressant (TCA) users are at an increased risk of NHL, but they did not examine the risk of specific NHL subtypes in association with TCA use. Because TCAs continue to be widely used, and because of the etiologic heterogeneity across subtypes in this common class of cancers, an assessment of NHL incidence in TCA users represents an important undertaking.