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dc.contributor.authorSavas, Sevtap
dc.contributor.authorSchmidt, Steffen
dc.contributor.authorJarjanazi, Hamdi
dc.contributor.authorOzcelik, Hilmi
dc.date.accessioned2009-04-06T07:57:39Z
dc.date.available2009-04-06T07:57:39Z
dc.date.issued2006-03
dc.identifier.citationHum. Genomics 2006, 2 (5):287-296en
dc.identifier.issn1479-7364
dc.identifier.pmid16595073
dc.identifier.urihttp://hdl.handle.net/10146/64473
dc.descriptionKEYWORDS CLASSIFICATION: biomarkers of individual susceptibility: validation;Breast Neoplasms;Canada;Carcinogenicity Tests;epidemiology;Female;genetics;Genes,Brca1;Genes,Brca2;Genes,Tumor Suppressor;Genetics,Population;Humans;Polymorphism,Single Nucleotide;Predictive Value of Tests;Research;Risk Factors;Variation (Genetics).en
dc.description.abstractAlthough highly penetrant alleles of BRCA1 and BRCA2 have been shown to predispose to breast cancer, the majority of breast cancer cases are assumed to result from the presence of low-moderate penetrant alleles and environmental carcinogens. Non-synonymous single nucleotide polymorphisms (nsSNPs) are hypothesised to contribute to disease susceptibility and approximately 30 per cent of them are predicted to have a biological significance. In this study, we have applied a bioinformatics-based strategy to identify breast cancer-related nsSNPs from 981 carcinogenesis-related genes expressed in breast tissue. Our results revealed a total of 367 validated nsSNPs, 109 (29.7 per cent) of which are predicted to affect the protein function (functional nsSNPs), suggesting that these nsSNPs are likely to influence the development and homeostasis of breast tissue and hence contribute to breast cancer susceptibility. Sixty-seven of the functional nsSNPs presented as commonly occurring nsSNPs (minor allele frequencies > or =5 per cent), representing excellent candidates for breast cancer susceptibility. Additionally, a non-uniform distribution of the common functional nsSNPs among different human populations was observed: 15 nsSNPs were reported to be present in all populations analysed, whereas another set of 15 nsSNPs was specific to particular population(s). We propose that the nsSNPs analysed in this study constitute a unique resource of potential genetic factors for breast cancer susceptibility. Furthermore, the variations in functional nsSNP allele frequencies across major population backgrounds may point to the potential variability of the molecular basis of breast cancer predisposition and treatment response among different human populations.
dc.language.isoenen
dc.relation.urlhttp://henrystewart.metapress.com/app/home/contribution.asp?referrer=parent&backto=issue,4,9;journal,4,14;linkingpublicationresults,1:121141,1en
dc.subjectBreast cancer predispositionen
dc.subjectnsSNPsen
dc.subjectBreast tissue expressionen
dc.subjectCarcinogenesis-related genesen
dc.subjectPolyPhenen
dc.subject.meshBreast Neoplasms
dc.subject.meshCarcinogenicity Tests
dc.subject.meshFemale
dc.subject.meshGenes, BRCA1
dc.subject.meshGenes, BRCA2
dc.subject.meshGenes, Tumor Suppressor
dc.subject.meshGenetic Variation
dc.subject.meshGenetics, Population
dc.subject.meshHumans
dc.subject.meshPolymorphism, Single Nucleotide
dc.subject.meshPredictive Value of Tests
dc.subject.meshRisk Factors
dc.titleFunctional nsSNPs from carcinogenesis-related genes expressed in breast tissue: potential breast cancer risk alleles and their distribution across human populations.en
dc.typeArticleen
dc.identifier.journalHuman genomicsen
html.description.abstractAlthough highly penetrant alleles of BRCA1 and BRCA2 have been shown to predispose to breast cancer, the majority of breast cancer cases are assumed to result from the presence of low-moderate penetrant alleles and environmental carcinogens. Non-synonymous single nucleotide polymorphisms (nsSNPs) are hypothesised to contribute to disease susceptibility and approximately 30 per cent of them are predicted to have a biological significance. In this study, we have applied a bioinformatics-based strategy to identify breast cancer-related nsSNPs from 981 carcinogenesis-related genes expressed in breast tissue. Our results revealed a total of 367 validated nsSNPs, 109 (29.7 per cent) of which are predicted to affect the protein function (functional nsSNPs), suggesting that these nsSNPs are likely to influence the development and homeostasis of breast tissue and hence contribute to breast cancer susceptibility. Sixty-seven of the functional nsSNPs presented as commonly occurring nsSNPs (minor allele frequencies > or =5 per cent), representing excellent candidates for breast cancer susceptibility. Additionally, a non-uniform distribution of the common functional nsSNPs among different human populations was observed: 15 nsSNPs were reported to be present in all populations analysed, whereas another set of 15 nsSNPs was specific to particular population(s). We propose that the nsSNPs analysed in this study constitute a unique resource of potential genetic factors for breast cancer susceptibility. Furthermore, the variations in functional nsSNP allele frequencies across major population backgrounds may point to the potential variability of the molecular basis of breast cancer predisposition and treatment response among different human populations.


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