Molecular pathological epidemiology of colorectal neoplasia: an emerging transdisciplinary and interdisciplinary field
TLDR
Molecular pathologic epidemiology is overviewed, which is a multidisciplinary field of investigations of the inter-relationship between exogenous and endogenous factors, tumoural molecular signatures and tumour progression, and integrating genome-wide association studies (GWAS) with molecular pathological investigation is a promising area.Abstract:
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 on a genome-wide scale. Activation of oncogenes including KRAS, BRAF and PIK3CA affects intracellular signalling 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 and pathologic process, somatic molecular changes and tumour biomarkers have been studied in relation to the exposure of interest. Moreover, an investigation of interactive effects of tumour molecular changes and the exposures of interest on tumour behaviour (prognosis or clinical outcome) can lead to a better understanding of tumour 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 inter-relationship between exogenous and endogenous (eg, genetic) factors, tumoural molecular signatures and tumour progression. Furthermore, integrating genome-wide association studies (GWAS) with molecular pathological investigation is a promising area (GWAS-MPE approach). 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 pathological epidemiology has unique strengths, and can provide insights into the pathogenic process and help optimise personalised 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.read more
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Aspirin use, tumor PIK3CA mutation, and colorectal-cancer survival.
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Cancer classification using the Immunoscore: a worldwide task force
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Fusobacterium nucleatum in colorectal carcinoma tissue and patient prognosis
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TL;DR: The amount of F. nucleatum DNA in colorectal cancer tissue is associated with shorter survival, and may potentially serve as a prognostic biomarker, which may have implications in developing cancer prevention and treatment strategies through targeting GI microflora by diet, probiotics and antibiotics.
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Meta-analysis of fecal metagenomes reveals global microbial signatures that are specific for colorectal cancer
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TL;DR: A meta-analysis of eight geographically and technically diverse fecal shotgun metagenomic studies of colorectal cancer identified a core set of 29 species significantly enriched in CRC metagenomes, establishing globally generalizable, predictive taxonomic and functional microbiome CRC signatures as a basis for future diagnostics.
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