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Molecular Pathologic Epidemiology of Colorectal Neoplasia: An Emerging Transdisciplinary and Interdisciplinary Field

机译：结直肠瘤的分子病理流行病学：一种新兴跨学科和跨学科领域

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Colorectal cancer is a complex disease resulting from somatic genetic and epigenetic alterations, including locus-specific CpG island methylation and global DNA or LINE-1 hypomethylation. Global molecular characteristics such as microsatellite instability (MSI), CpG island methylator phenotype (CIMP), global DNA hypomethylation, and chromosomal instability cause alterations of gene function in a genome-wide scale. Activation of oncogenes including KRAS, BRAF and PIK3CA affects intracellular signaling pathways and has been associated with CIMP and MSI. Traditional epidemiology research has investigated various factors in relation to an overall risk of colon and/or rectal cancer. However, colorectal cancers comprise a heterogeneous group of diseases with different sets of genetic and epigenetic alterations. To better understand how a particular exposure influences the carcinogenic process, somatic molecular changes and tumor biomarkers have been studied in relation to the exposure of interest. Moreover, an investigation of interactive effects of tumor molecular changes and the exposures of interest on tumor behavior (prognosis or clinical outcome) can lead to a better understanding of tumor molecular changes, which may be prognostic or predictive tissue biomarkers. These new research efforts represent “Molecular Pathologic Epidemiology”, which is a multidisciplinary field of investigations of the interrelationship between exogenous and endogenous (e.g., genetic) factors, tumoral molecular signatures and tumor progression. Furthermore, integrating genome-wide association studies (GWAS) with molecular pathologic investigation is a promising area. Examining the relationship between susceptibility alleles identified by GWAS and specific molecular alterations can help elucidate the function of these alleles and provide insights into whether susceptibility alleles are truly causal. Although there are challenges, molecular pathologic epidemiology has unique strengths, and can provide insights into the pathogenic process and help optimize personalized prevention and therapy. In this review, we overview this relatively new field of research and discuss measures to overcome challenges and move this field forward.

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