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Am J Gastroenterol. 2014 Aug;109(8):1205-14. doi: 10.1038/ajg.2014.153. Epub 2014 Jun 17.

Progress and opportunities in molecular pathological epidemiology of colorectal premalignant lesions.

Author information

1
1] Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK [2] The first two authors contributed equally to this work.
2
1] Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA [2] Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, USA [3] The first two authors contributed equally to this work.
3
1] Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, USA [2] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA [3] Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA.
4
1] Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, USA [2] Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA.
5
Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA.
6
1] Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA [2] Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA.
7
Department of Pathology, Boston University Medical Center, Boston, Massachusetts, USA.
8
1] Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA [2] Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA [3] Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, USA.

Abstract

Molecular pathological epidemiology (MPE) is an integrative molecular and population health science that addresses the molecular pathogenesis and heterogeneity of disease processes. The MPE of colonic and rectal premalignant lesions (including hyperplastic polyps, tubular adenomas, tubulovillous adenomas, villous adenomas, traditional serrated adenomas, sessile serrated adenomas/sessile serrated polyps, and hamartomatous polyps) can provide unique opportunities for examining the influence of diet, lifestyle, and environmental exposures on specific pathways of carcinogenesis. Colorectal neoplasia can provide a practical model by which both malignant epithelial tumor (carcinoma) and its precursor are subjected to molecular pathological analyses. KRAS, BRAF, and PIK3CA oncogene mutations, microsatellite instability, CpG island methylator phenotype, and LINE-1 methylation are commonly examined tumor biomarkers. Future opportunities include interrogation of comprehensive genomic, epigenomic, or panomic datasets, and the adoption of in vivo pathology techniques. Considering the colorectal continuum hypothesis and emerging roles of gut microbiota and host immunity in tumorigenesis, detailed information on tumor location is important. There are unique strengths and caveats, especially with regard to case ascertainment by colonoscopy. The MPE of colorectal premalignant lesions can identify etiologic exposures associated with neoplastic initiation and progression, help us better understand colorectal carcinogenesis, and facilitate personalized prevention, screening, and therapy.

PMID:
24935274
PMCID:
PMC4125459
DOI:
10.1038/ajg.2014.153
[Indexed for MEDLINE]
Free PMC Article

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