Progress and Opportunities in Molecular Pathological Epidemiology of Colorectal Premalignant Lesions

Abstract

Molecular pathological epidemiology (MPE) is integrative molecular and population health science to address molecular pathogenesis and heterogeneity of disease processes. MPE of colon 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 to examine the influence of diet, lifestyle and environmental exposures on specific pathways of carcinogenesis. Colorectal neoplasia can provide a practical model where both malignant epithelial tumor (carcinoma), and its precursor, are subjected to molecular pathology 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 comprehensive interrogation of genomics, epigenomics and pan-omics, as well as in vivo pathology analyses of tissue microenvironment, molecular networks and interactome by endomicroscopy. Considering the colorectal continuum hypothesis and emerging roles of gut microbiota and host immunity in tumorigenesis, detailed tumor location is important information. There are unique strengths and caveats, especially with regard to case ascertainment by colonoscopy. 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.

The Evolving Role of Nonsteroidal Anti-Inflammatory Drugs in Colon Cancer Prevention: A Cause for Optimism

“…In this context, it is reasonable to expect a substantial contribution from molecular epidemiology, an integrative molecular and population health science that addresses the molecular pathogenesis and heterogeneity of diseases. Molecular pathologic analyses of CRC and especially its precursor lesions could facilitate personalized prevention (Lochhead et al, 2014).…”

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“…To date, most of MPE research is applied to cancer [81,82] , but this approach may also be important to UGIB and further investigation is needed to evaluate its contribution.…”

High-Risk Human Papillomavirus and Colorectal Carcinogenesis

“…Chromosomal instability can be demonstrated in late precursor adenomas. In this sequence, APC mutation is a common early event, while the serrated lesions commonly have BRAF or KRAS mutation [31]. Other risk factors include diet and lifestyle (such as consumption of red meat, smoking, excessive alcohol, weight gain, etc.)…”

“…Pathologic entities include tubular adenoma, tubulovillous adenoma, villous adenoma, hyperplastic polyp, sessile serrated adenoma, sessile serrated polyp, and traditional serrated adenoma. In addition, some hamartomatous polyps are considered premalignant lesions [31]. Among precancerous polyps adenomatous and advanced adenomatous polyps that have polyp size >10 mm, in addition to villous/tubulovillous histological features, or having high-grade dysplasia (HGD), are found to have an increased prevalence and incidence in the elderly [26], and have a potential to progress to invasive adenocarcinomas [26,32].…”