Molecular pathological epidemiology gives clues to paradoxical findings.
Molecular pathological epidemiology gives clues to paradoxical findings.
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DOI：
10.1007/s10654-015-0088-4
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发表时间：
2015-10
影响因子：
13.6
通讯作者：
Ogino S
中科院分区：
文献类型：
--
作者：
Nishihara R;VanderWeele TJ;Shibuya K;Mittleman MA;Wang M;Field AE;Giovannucci E;Lochhead P;Ogino S
一些流行病学研究已经描述了似乎是矛盾的关联，其中观察到疾病发生率的某些明确的风险因素与患有该疾病的患者的有利临床结果之间的不一致关系。例如，“肥胖悖论”代表了肥胖与患有某种疾病（如冠心病）的患者的生存率之间的关联。Paranoical观察结果引起了令人烦恼的临床和公共卫生问题，因为它们提出了因果关系的问题，并阻碍了有效干预措施的发展。令人信服的证据表明，致病过程包括细胞和微环境内的分子改变，受到各种外源性和内源性暴露的影响，并且在患有任何特定疾病的患者中存在分子病理学和病理生理学的人际异质性。本文介绍了分子病理流行病学（MPE）这一新兴的综合性跨学科领域的研究方法，MPE是建立在独特的疾病原理和疾病连续体理论基础上的。我们利用MPE方法和现有的肿瘤体细胞遗传学和表观遗传学特征的文献数据，分析和破译明显的矛盾结果。通过我们对结直肠癌、肾细胞癌和胶质母细胞瘤（恶性脑肿瘤）的分析，我们可以很容易地解释疾病风险因素与疾病患者预后良好之间的矛盾关系。MPE范式和方法不仅可以应用于肿瘤，而且可以应用于各种非肿瘤性疾病，其中存在无可争议的普遍存在的发病机制和分子病理学异质性。包括考虑疾病异质性的MPE范式在精准医学和公共卫生的进步中起着至关重要的作用。
A number of epidemiologic studies have described what appear to be paradoxical associations, where an incongruous relationship is observed between a certain well-established risk factor for disease incidence and favorable clinical outcome among patients with that disease. For example, the “obesity paradox” represents the association between obesity and better survival among patients with a certain disease such as coronary heart disease. Paradoxical observations cause vexing clinical and public health problems as they raise questions on causal relationships and hinder the development of effective interventions. Compelling evidence indicates that pathogenic processes encompass molecular alterations within cells and the microenvironment, influenced by various exogenous and endogenous exposures, and that interpersonal heterogeneity in molecular pathology and pathophysiology exists among patients with any given disease. In this article, we introduce methods of the emerging integrative interdisciplinary field of molecular pathological epidemiology (MPE), which is founded on the unique disease principle and disease continuum theory. We analyze and decipher apparent paradoxical findings, utilizing the MPE approach and available literature data on tumor somatic genetic and epigenetic characteristics. Through our analyses in colorectal cancer, renal cell carcinoma, and glioblastoma (malignant brain tumor), we can readily explain paradoxical associations between disease risk factors and better prognosis among disease patients. The MPE paradigm and approach can be applied to not only neoplasms but also various non-neoplastic diseases where there exists indisputable ubiquitous heterogeneity of pathogenesis and molecular pathology. The MPE paradigm including consideration of disease heterogeneity plays an essential role in advancements of precision medicine and public health.