Statistical methods for studying disease subtype heterogeneity
Top Cited Papers
- 1 December 2015
- journal article
- tutorial in-biostatistics
- Published by Wiley in Statistics in Medicine
- Vol. 35 (5), 782-800
- https://doi.org/10.1002/sim.6793
Abstract
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, and 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. Copyright © 2015 John Wiley & Sons, Ltd.Keywords
Funding Information
- National Institutes of Health (R01 CA151993, UM1 CA167552, P01 CA55075, P01 CA87969, UM1 CA186107, R01 CA137178, R35 CA197735)
- National Institutes of Health (R01 CA151993, UM1 CA167552, P01 CA55075, P01 CA87969, UM1 CA186107, R01 CA137178, R35 CA197735)
This publication has 97 references indexed in Scilit:
- A Subset-Based Approach Improves Power and Interpretation for the Combined Analysis of Genetic Association Studies of Heterogeneous TraitsAmerican Journal of Human Genetics, 2012
- Body size and risk for colorectal cancers showing BRAF mutations or microsatellite instability: a pooled analysisInternational Journal of Epidemiology, 2012
- A strategy for distinguishing optimal cancer subtypesInternational Journal of Cancer, 2010
- Analysis of cohort studies with multivariate and partially observed disease classification dataBiometrika, 2010
- Case–Control Study of Overweight, Obesity, and Colorectal Cancer Risk, Overall and by Tumor Microsatellite Instability StatusJNCI Journal of the National Cancer Institute, 2010
- Ensuring long-term sustainability of existing cohorts remains the highest priority to inform cancer prevention and controlCancer Causes & Control, 2010
- Risk Factors for Epithelial Ovarian Cancer by Histologic SubtypeAmerican Journal of Epidemiology, 2009
- The MLH1 −93 G>A promoter polymorphism and genetic and epigenetic alterations in colon cancerGenes, Chromosomes and Cancer, 2008
- Criteria for the Evaluation of Large Cohort Studies: An Application to the Nurses’ Health StudyJNCI Journal of the National Cancer Institute, 2008
- Advanced methods in meta‐analysis: multivariate approach and meta‐regressionStatistics in Medicine, 2002