Statistical methods for studying disease subtype heterogeneity.
Statistical methods for studying disease subtype heterogeneity.
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DOI：
10.1002/sim.6793
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发表时间：
2016-02-28
影响因子：
2
通讯作者：
Ogino S
中科院分区：
文献类型：
--
作者：
Wang M;Spiegelman D;Kuchiba A;Lochhead P;Kim S;Chan AT;Poole EM;Tamimi R;Tworoger SS;Giovannucci E;Rosner B;Ogino S
流行病学研究的一个基本目标是调查暴露与疾病风险之间的关系。这种疾病的病例通常被认为是单一的结果，并被认为具有共同的病因。然而，有证据表明，许多人类疾病的产生和进化是通过一系列异质分子病理过程，受不同暴露的影响。在各种肿瘤，如结直肠癌、肺癌、前列腺癌和乳腺癌、白血病和淋巴瘤，以及非肿瘤性疾病，包括肥胖、2型糖尿病、青光眼、中风、心血管疾病、自闭症和自身免疫性疾病中，已经考虑到致病异质性。在本文中，我们讨论了研究疾病亚型异质性的分析选择，强调了评估潜在危险因素与疾病的关联是否因疾病亚型而异的方法。方法描述了疾病亚型是分类和顺序的情况，以及队列研究，匹配和不匹配的病例对照研究以及病例-病例研究设计。为了说明这一点，我们将这些方法应用于通过肿瘤LINE-1甲基化亚型对酒精摄入和结肠癌风险的分子病理流行病学研究。实现这些方法的用户友好软件是公开可用的。
A fundamental goal of epidemiologic research is to investigate the relationship between exposures and disease risk. Cases of the disease are often considered a single outcome, and assumed to share a common etiology. However, evidence indicates that many human diseases arise and evolve through a range of heterogeneous molecular pathologic processes, influenced by diverse exposures. Pathogenic heterogeneity has been considered in various neoplasms such as colorectal, lung, prostate, and breast cancers, leukemia and lymphoma, as well as non-neoplastic diseases, including obesity, type II diabetes, glaucoma, stroke, cardiovascular disease, autism and autoimmune disease. In this article, we discuss analytic options for studying disease subtype heterogeneity, emphasizing methods for evaluating whether the association of a potential risk factor with disease varies by disease subtype. Methods are described for scenarios where disease subtypes are categorical and ordinal, and for cohort studies, matched and unmatched case-control studies, and case-case study designs. For illustration, we apply the methods to a molecular pathological epidemiology study of alcohol intake and colon cancer risk by tumor LINE-1 methylation subtypes. User-friendly software to implement the methods is publicly available.