Linked Life Data

21036793

Source:http://linkedlifedata.com/resource/pubmed/id/21036793

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2011-2-7
pubmed:abstractText
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1468-3288
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
60
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
397-411
pubmed:dateRevised
2011-6-13
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Molecular pathological epidemiology of colorectal neoplasia: an emerging transdisciplinary and interdisciplinary field.
pubmed:affiliation
Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. shuji_ogino@dfci.harvard.edu
pubmed:publicationType
Journal Article, Review, Research Support, N.I.H., Extramural