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Proceedings of the Third International Molecular Pathological Epidemiology (MPE) Meeting Cancer Causes Control (2017) 28:167–176 DOI 10.1007/s10552-016-0845-z REVIEW Proceedings of the third international molecular pathological epidemiology (MPE) meeting Peter T. Campbell1 · Timothy R. Rebbeck2,3 · Reiko Nishihara3,4 · Andrew H. Beck5,6 · Colin B. Begg7 · Alexei A. Bogdanov8 · Yin Cao4,9,10 · Helen G. Coleman11 · Gordon J. Freeman3 · Yujing J. Heng5,6 · Curtis Huttenhower12,13 · Rafael A. Irizarry12,14 · N. Sertac Kip15 · Franziska Michor12,14 · Daniel Nevo2,12 · Ulrike Peters16,17 · Amanda I. Phipps16,17 · Elizabeth M. Poole2,18 · Zhi Rong Qian3 · John Quackenbush12,14 · Harlan Robins16 · Peter K. Rogan19 · Martha L. Slattery20 · Stephanie A. Smith‑Warner2,4 · Mingyang Song4,9 · Tyler J. VanderWeele2 · Daniel Xia21 · Emily C. Zabor7 · Xuehong Zhang18 · Molin Wang2 · Shuji Ogino2,3,22,23 Received: 30 September 2016 / Accepted: 20 December 2016 / Published online: 17 January 2017 © Springer International Publishing Switzerland 2017 Abstract Molecular pathological epidemiology (MPE) research has been commonly applied to investigating is a transdisciplinary and relatively new scientific disci- breast, lung, and colorectal cancers, its methodology can be pline that integrates theory, methods, and resources from used to study most diseases. Recent successes in MPE stud- epidemiology, pathology, biostatistics, bioinformatics, and ies include: (1) the development of new statistical methods computational biology. The underlying objective of MPE to address etiologic heterogeneity; (2) the enhancement research is to better understand the etiology and progres- of causal inference; (3) the identification of previously sion of complex and heterogeneous human diseases with unknown exposure-subtype disease associations; and (4) the goal of informing prevention and treatment efforts in better understanding of the role of lifestyle/behavioral population health and clinical medicine. Although MPE factors on modifying prognosis according to disease sub- type. Central challenges to MPE include the relative lack of transdisciplinary experts, educational programs, and P. T. Campbell and S. Ogino contributed equally to this work. * Peter T. Campbell Curtis Huttenhower [email protected] [email protected] * Shuji Ogino Rafael A. Irizarry [email protected] [email protected] Timothy R. Rebbeck N. Sertac Kip [email protected] [email protected] Reiko Nishihara Franziska Michor [email protected]; [email protected]. [email protected] edu Daniel Nevo Andrew H. Beck [email protected] [email protected] Ulrike Peters Colin B. Begg [email protected] [email protected] Amanda I. Phipps Alexei A. Bogdanov [email protected] [email protected] Elizabeth M. Poole Yin Cao [email protected] [email protected] Zhi Rong Qian Helen G. Coleman [email protected] [email protected] John Quackenbush Gordon J. Freeman [email protected] [email protected] Harlan Robins Yujing J. Heng [email protected] [email protected] Vol.:(0123456789)1 3 168 Cancer Causes Control (2017) 28:167–176 forums to discuss issues related to the advancement of the and epidemiology was first described in the literature [1]. field. To address these challenges, highlight recent suc- Since then, the field of MPE has expanded considerably to cesses in the field, and identify new opportunities, a series advance population health sciences [2–4]. of MPE meetings have been held at the Dana–Farber Can- As a subdiscipline of epidemiology, MPE studies cer Institute in Boston, MA. Herein, we share the proceed- are usually drawn from larger prospective cohort (e.g., ings of the Third International MPE Meeting, held in May Nurses’ Health Study, Cancer Prevention Study-II) or 2016 and attended by 150 scientists from 17 countries. case-control (e.g., Breast and Colon Cancer Family Reg- Special topics included integration of MPE with immunol- istries) studies that are supported to collect and to use ogy and health disparity research. This meeting series will pathology specimens. In an MPE paradigm, a potential continue to provide an impetus to foster further transdisci- etiologic factor is assessed with risk of an outcome across plinary integration of divergent scientific fields. strata of molecular characteristics for the disease-of- interest. More recently, MPE resources have matured to Keywords Molecular pathological epidemiology · allow examination of the independent and joint influences Meeting report · Proceedings of endogenous/lifestyle/behavioral factors and tissue- based molecular markers on patient prognosis and related outcomes [5]. The underlying premise with an incidence Introduction study in an MPE paradigm is that diseases which have certain molecular perturbations in common are more Molecular pathological epidemiology (MPE) is an inte- likely to share a common cause (or causes); similarly, grative scientific discipline that examines the interplay of for survival studies, it is postulated that endogenous/life- risk and prognostic factors with pathology tissue-based style/behavioral factors differentially influence prognosis biomarkers of health and disease in human populations. according to molecular signatures of the disease, because Although molecular pathology had been integrated into those factors likely interact with the diseased cells in the epidemiologic research for decades, it was only in 2010 local microenvironment. To date, MPE has been largely when the integrative field that unified molecular pathology employed as a method to assess neoplastic disease Peter K. Rogan 5 Cancer Research Institute, Beth Israel Deaconess Cancer [email protected] Center, Boston, MA, USA Martha L. Slattery 6 Department of Pathology, Harvard Medical School, Beth [email protected] Israel Deaconess Medical Center, Boston, MA, USA Stephanie A. Smith-Warner 7 Department of Epidemiology and Biostatistics, Memorial [email protected] Sloan Kettering Cancer Center, New York, NY, USA Mingyang Song 8 Department of Radiology, University of Massachusetts [email protected] Medical School, Worcester, MA, USA Tyler J. VanderWeele 9 Clinical and Translational Epidemiology Unit, Massachusetts [email protected] General Hospital and Harvard Medical School, Boston, MA, USA Daniel Xia [email protected] 10 Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA Emily C. Zabor [email protected] 11 Epidemiology and Health Services Research Group, Centre for Public Health, Queens University Belfast, Belfast, Xuehong Zhang Northern Ireland [email protected] 12 Department of Biostatistics, Harvard T.H. Chan School Molin Wang of Public Health, Boston, MA, USA [email protected] 13 Microbial Systems and Communities, Genome Sequencing 1 Epidemiology Research Program, American Cancer Society, and Analysis Program, The Broad Institute, Cambridge, MA, 250 Williams Street NW, Atlanta, GA 30303, USA USA 2 Department of Epidemiology, Harvard T.H. Chan School 14 Department of Biostatistics and Computational Biology, of Public Health, Boston, MA, USA Dana-Farber Cancer Institute, Boston, MA, USA 3 Department of Medical Oncology, Dana-Farber Cancer 15 Laboratory Medicine and Pathology, Geisinger Health Institute, Harvard Medical School, Boston, MA, USA System, Danville, PA, USA 4 Department of Nutrition, Harvard T.H. Chan School 16 Public Health Sciences Division, Fred Hutchinson Cancer of Public Health, Boston, MA, USA Research Center, Seattle, WA, USA 1 3 Cancer Causes Control (2017) 28:167–176 169 heterogeneity (e.g., cancers of the colorectum, breast, and consistently null associations have been shown for colorec- lung, in particular); however, MPE methods are broadly tal cancers not bearing those phenotypes [21–24]. Beyond applicable to examining any complex disease or health identifying previously unknown exposure-subtype disease condition [6]. The MPE concept as a single, integrative associations and supporting causality, MPE studies may field has obtained increased recognition in recent years also identify disease subtypes that benefit from certain [7–16] due to the increased ability to molecularly charac- behavioral or pharmacologic interventions and discover/ terize tumors. validate molecular markers for risk assessment, early detec- One of the leading opportunities in MPE research is tion, prognosis, and prediction [6]. the ability to better predict disease occurrence and prog- MPE studies also have several limitations that are com- nosis compared to the more conventional disease enti- mon to observational research, in general, and to epidemi- ties without molecular classification. The evidence link- ology in particular when subgroup analyses are performed, ing cigarette smoking and colorectal cancer illustrates including the potential for bias (e.g., selection bias), limited this point. Whereas the association between smoking and generalizability, low statistical power (and the related issue lung cancer is robust, with relative risks (RRs) that often of low risk estimate precision), multiple testing leading to approach 10 when comparing long-term smokers to non- potentially spurious findings, and the potential for measure- smokers [17], the link between smoking and colorectal can- ment errors of the molecular phenotypes of interest. MPE cer overall is much more modest, with RRs usually below also faces unique challenges, including the lack of research- 1.2 [18]. Indeed,
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