Molecular pathological epidemiology

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Molecular pathological epidemiology (MPE, also molecular pathologic epidemiology) is a discipline combining epidemiology and pathology. It is defined as "epidemiology of molecular pathology and heterogeneity of disease". [1] Pathology and epidemiology share the same goal of elucidating etiology of disease, and MPE aims to achieve this goal at molecular, individual and population levels. Typically, MPE utilizes tissue pathology resources and data within existing epidemiology studies. Molecular epidemiology broadly encompasses MPE and conventional-type molecular epidemiology with the use of traditional disease designation systems.

Contents

Disease process

Data from The Cancer Genome Atlas projects indicate that disease evolution is an inherently heterogeneous process. [2] [3] Each patient has a unique disease process (“the unique disease principle”), considering the uniqueness of the exposome and its unique influence on molecular pathologic process. [2] This concept has been adopted in clinical medicine along with precision medicine and personalized medicine.[ citation needed ]

Methodology

In MPE, investigators dissect interrelationships between exposures (e.g., environmental, dietary, lifestyle and genetic factors); alterations in cellular or extracellular molecules (disease molecular signatures); and disease evolution and progression. [2] Investigators can analyze genome, methylome, epigenome, metabolome, transcriptome, proteome, microbiome, immunity and interactome. A putative risk factor can be linked to specific molecular signatures.[ citation needed ]

MPE research enables identification of a new biomarker for potential clinical utility, using large-scale population-based data (e.g., PIK3CA mutation in colorectal cancer to select patients for aspirin therapy). [1] The MPE approach can be used following a genome-wide association study (GWAS), termed "GWAS-MPE approach". [4] Detailed disease endpoint phenotyping can be conducted by means of molecular pathology or surrogate histopathology or immunohistochemistry analysis of diseased tissues and cells within GWAS. [5] [6]

As an alternative approach, potential risk variants identified by GWAS can be examined in combination with molecular pathology analysis on diseased tissues. [7] [8] [9] [10] This GWAS-MPE approach can give not only more precise effect estimates, even larger effects, for specific molecular subtypes of the disease, but also insights into pathogenesis by linking genetic variants to molecular pathologic signatures of disease. [4] Since molecular diagnostics is becoming routine clinical practice, molecular pathology data can aid epidemiologic research.[ citation needed ]

History

MPE began as analysis of risk factors (e.g., smoking) and molecular pathological findings (e.g., KRAS G12C oncogene mutations in lung carcinoma).[ citation needed ]

Studies to examine the relationship between an exposure and molecular pathological signatures of disease (particularly, cancer) became increasingly common throughout the 1990s and early 2000s. [11]

The use of molecular pathology in epidemiology lacked standardized methodologies and guidelines as well as interdisciplinary experts and training programs. [12] MPE research required a new conceptual framework and methodologies (epidemiological method) because MPE examines heterogeneity in an outcome variable. [13]

The term "molecular pathological epidemiology" was used by Shuji Ogino and Meir Stampfer in 2010. [14] Specific principles of MPE developed following 2010. The MPE paradigm is in widespread use globally, [15] [16] [17] [18] [19] [20] [21] [22] [23] [24] [25] [ excessive citations ] and has been a subject of international conferences. [26] [27] [28] The International Molecular Pathological Epidemiology (MPE) Meeting Series, which was established in 2013, has been open to the research community around the world, and five meetings were held through 2021. [29] [30] [31] [32]

See also

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Shuji Ogino is a molecular pathological epidemiologist, pathologist, and epidemiologist. He is currently Professor of Pathology at Harvard Medical School and Brigham and Women's Hospital, and Professor in the Department of Epidemiology at Harvard T.H. Chan School of Public Health. He is also Chief of Program in MPE Molecular Pathological Epidemiology at Brigham and Women's Hospital, and an associate member of Broad Institute of MIT and Harvard. He has been known for his work on establishing a new discipline, molecular pathological epidemiology, which represents an interdisciplinary science of molecular pathology and epidemiology.

References

  1. 1 2 Ogino S, Lochhead P, Giovannucci E, Meyerhardt JA, Fuchs CS, Chan AT (June 2014). "Discovery of colorectal cancer PIK3CA mutation as potential predictive biomarker: power and promise of molecular pathological epidemiology". review. Oncogene. 33 (23): 2949–55. doi:10.1038/onc.2013.244. PMC   3818472 . PMID   23792451.
  2. 1 2 3 Ogino S, Lochhead P, Chan AT, Nishihara R, Cho E, Wolpin BM, et al. (April 2013). "Molecular pathological epidemiology of epigenetics: emerging integrative science to analyze environment, host, and disease". review. Modern Pathology. 26 (4): 465–84. doi:10.1038/modpathol.2012.214. PMC   3637979 . PMID   23307060.
  3. ↑ Ogino S, Fuchs CS, Giovannucci E (2012). "How many molecular subtypes? Implications of the unique tumor principle in personalized medicine". review. Expert Review of Molecular Diagnostics. 12 (6): 621–8. doi:10.1586/erm.12.46. PMC   3492839 . PMID   22845482.
  4. 1 2 Ogino S, Chan AT, Fuchs CS, Giovannucci E (March 2011). "Molecular pathological epidemiology of colorectal neoplasia: an emerging transdisciplinary and interdisciplinary field". review. Gut. 60 (3): 397–411. doi:10.1136/gut.2010.217182. PMC   3040598 . PMID   21036793.
  5. ↑ Shen H, Fridley BL, Song H, Lawrenson K, Cunningham JM, Ramus SJ, et al. (2013). "Epigenetic analysis leads to identification of HNF1B as a subtype-specific susceptibility gene for ovarian cancer". primary. Nature Communications. 4: 1628. Bibcode:2013NatCo...4.1628.. doi:10.1038/ncomms2629. PMC   3848248 . PMID   23535649.
  6. ↑ Garcia-Closas M, Couch FJ, Lindstrom S, Michailidou K, Schmidt MK, Brook MN, et al. (April 2013). "Genome-wide association studies identify four ER negative-specific breast cancer risk loci". primary. Nature Genetics. 45 (4): 392–8, 398e1-2. doi:10.1038/ng.2561. PMC   3771695 . PMID   23535733.
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  12. ↑ Sherman ME, Howatt W, Blows FM, Pharoah P, Hewitt SM, Garcia-Closas M (April 2010). "Molecular pathology in epidemiologic studies: a primer on key considerations". review. Cancer Epidemiology, Biomarkers & Prevention. 19 (4): 966–72. doi:10.1158/1055-9965.EPI-10-0056. PMC   2852464 . PMID   20332257.
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  16. ↑ Galon J, Pagès F, Marincola FM, Angell HK, Thurin M, Lugli A, et al. (October 2012). "Cancer classification using the Immunoscore: a worldwide task force". review. Journal of Translational Medicine. 10: 205. doi: 10.1186/1479-5876-10-205 . PMC   3554496 . PMID   23034130.
  17. ↑ Ku CS, Cooper DN, Wu M, Roukos DH, Pawitan Y, Soong R, Iacopetta B (August 2012). "Gene discovery in familial cancer syndromes by exome sequencing: prospects for the elucidation of familial colorectal cancer type X". review. Modern Pathology. 25 (8): 1055–68. doi: 10.1038/modpathol.2012.62 . PMID   22522846.
  18. ↑ Koshiol J, Lin SW (July 2012). "Can tissue-based immune markers be used for studying the natural history of cancer?". review. Annals of Epidemiology. 22 (7): 520–30. doi:10.1016/j.annepidem.2012.03.001. PMC   3596808 . PMID   22481034.
  19. ↑ Dogan S, Shen R, Ang DC, Johnson ML, D'Angelo SP, Paik PK, et al. (November 2012). "Molecular epidemiology of EGFR and KRAS mutations in 3,026 lung adenocarcinomas: higher susceptibility of women to smoking-related KRAS-mutant cancers". primary. Clinical Cancer Research. 18 (22): 6169–77. doi:10.1158/1078-0432.CCR-11-3265. PMC   3500422 . PMID   23014527.
  20. ↑ Spitz MR, Caporaso NE, Sellers TA (December 2012). "Integrative cancer epidemiology--the next generation". Cancer Discovery. 2 (12): 1087–90. doi:10.1158/2159-8290.CD-12-0424. PMC   3531829 . PMID   23230187.
  21. ↑ Shanmuganathan R, Basheer NB, Amirthalingam L, Muthukumar H, Kaliaperumal R, Shanmugam K (January 2013). "Conventional and nanotechniques for DNA methylation profiling". review. The Journal of Molecular Diagnostics. 15 (1): 17–26. doi: 10.1016/j.jmoldx.2012.06.007 . PMID   23127612.
  22. ↑ Hughes LA, Melotte V, de Schrijver J, de Maat M, Smit VT, Bovée JV, et al. (October 2013). "The CpG island methylator phenotype: what's in a name?". review. Cancer Research. 73 (19): 5858–68. doi: 10.1158/0008-5472.CAN-12-4306 . PMID   23801749.
  23. ↑ Esterhuyse MM, Kaufmann SH (July 2013). "Diagnostic biomarkers are hidden in the infected host's epigenome". review. Expert Review of Molecular Diagnostics. 13 (6): 625–37. doi:10.1586/14737159.2013.811897. PMID   23895131. S2CID   3463193.
  24. ↑ Hagland HR, Søreide K (January 2015). "Cellular metabolism in colorectal carcinogenesis: Influence of lifestyle, gut microbiome and metabolic pathways". review. Cancer Letters. 356 (2 Pt A): 273–80. doi: 10.1016/j.canlet.2014.02.026 . PMID   24614287.
  25. ↑ Bishehsari F, Mahdavinia M, Vacca M, Malekzadeh R, Mariani-Costantini R (May 2014). "Epidemiological transition of colorectal cancer in developing countries: environmental factors, molecular pathways, and opportunities for prevention". review. World Journal of Gastroenterology. 20 (20): 6055–72. doi: 10.3748/wjg.v20.i20.6055 . PMC   4033445 . PMID   24876728.
  26. ↑ Kuller LH, Bracken MB, Ogino S, Prentice RL, Tracy RP (November 2013). "The role of epidemiology in the era of molecular epidemiology and genomics: Summary of the 2013 AJE-sponsored Society of Epidemiologic Research Symposium". American Journal of Epidemiology. 178 (9): 1350–4. doi:10.1093/aje/kwt239. PMC   3988450 . PMID   24105654.
  27. ↑ Epplein M, Bostick RM, Mu L, Ogino S, Braithwaite D, Kanetsky PA (2014). "Challenges and opportunities in international molecular cancer prevention research: An ASPO Molecular Epidemiology and the Environment and International Cancer Prevention Interest Groups Report". Cancer Epidemiology, Biomarkers & Prevention. 23 (11): 2613–7. doi:10.1158/1055-9965.EPI-14-0848. PMC   4221505 . PMID   25277796.
  28. ↑ Ogino S, Campbell PT, Nishihara R, Phipps AI, Beck AH, Sherman ME, et al. (2015). "Proceedings of the second international molecular pathological epidemiology (MPE) meeting". Cancer Causes & Control. 26 (7): 959–72. doi:10.1007/s10552-015-0596-2. PMC   4466011 . PMID   25956270.
  29. ↑ "The Ogino MPE lab". Dana-Farber Cancer Institute. Archived from the original on 2019-05-15. Retrieved 2020-04-07.
  30. ↑ Campbell PT, Rebbeck TR, Nishihara R, Beck AH, Begg CB, Bogdanov AA, et al. (2017). "Proceedings of the third international molecular pathological epidemiology (MPE) meeting". review. Cancer Causes & Control. 28 (2): 167–176. doi:10.1007/s10552-016-0845-z. PMC   5303153 . PMID   28097472.
  31. ↑ Campbell et al. Cancer Causes Cont 2019
  32. ↑ "Home". mpemeeting.org.

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