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Eleven Candidate Susceptibility Genes for Common Familial Colorectal Cancer
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نویسنده
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gylfe a.e. ,katainen r. ,kondelin j. ,tanskanen t. ,cajuso t. ,hänninen u. ,taipale j. ,taipale m. ,renkonen-sinisalo l. ,järvinen h. ,mecklin j.-p. ,kilpivaara o. ,pitkänen e. ,vahteristo p. ,tuupanen s. ,karhu a. ,aaltonen l.a.
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منبع
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plos genetics - 2013 - دوره : 9 - شماره : 10
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چکیده
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Hereditary factors are presumed to play a role in one third of colorectal cancer (crc) cases. however,in the majority of familial crc cases the genetic basis of predisposition remains unexplained. this is particularly true for families with few affected individuals. to identify susceptibility genes for this common phenotype,we examined familial cases derived from a consecutive series of 1514 finnish crc patients. ninety-six familial crc patients with no previous diagnosis of a hereditary crc syndrome were included in the analysis. eighty-six patients had one affected first-degree relative,and ten patients had two or more. exome sequencing was utilized to search for genes harboring putative loss-of-function variants,because such alterations are likely candidates for disease-causing mutations. eleven genes with rare truncating variants in two or three familial crc cases were identified: uaca,sfxn4,twsg1,psph,nudt7,znf490,prss37,ccdc18,pradc1,mrpl3,and akr1c4. loss of heterozygosity was examined in all respective cancer samples,and was detected in seven occasions involving four of the candidate genes. in all seven occasions the wild-type allele was lost (p = 0.0078) providing additional evidence that these eleven genes are likely to include true culprits. the study provides a set of candidate predisposition genes which may explain a subset of common familial crc. additional genetic validation in other populations is required to provide firm evidence for causality,as well as to characterize the natural history of the respective phenotypes. © 2013 gylfe et al.
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آدرس
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department of medical genetics,genome-scale biology research program,university of helsinki,helsinki, Finland, department of medical genetics,genome-scale biology research program,university of helsinki,helsinki, Finland, department of medical genetics,genome-scale biology research program,university of helsinki,helsinki, Finland, department of medical genetics,genome-scale biology research program,university of helsinki,helsinki, Finland, department of medical genetics,genome-scale biology research program,university of helsinki,helsinki, Finland, department of medical genetics,genome-scale biology research program,university of helsinki,helsinki, Finland, institute of biomedicine,genome-scale biology research program,university of helsinki,helsinki,finland,science for life center,department of biosciences and nutrition,karolinska institutet,stockholm, Sweden, institute of biomedicine,genome-scale biology research program,university of helsinki,helsinki,finland,science for life center,department of biosciences and nutrition,karolinska institutet,stockholm, Sweden, department of surgery,helsinki university hospital,helsinki, Finland, department of surgery,helsinki university hospital,helsinki, Finland, department of surgery,jyväskylä central hospital,university of eastern finland,jyväskylä, Finland, department of medical genetics,genome-scale biology research program,university of helsinki,helsinki, Finland, department of medical genetics,genome-scale biology research program,university of helsinki,helsinki, Finland, department of medical genetics,genome-scale biology research program,university of helsinki,helsinki, Finland, department of medical genetics,genome-scale biology research program,university of helsinki,helsinki, Finland, department of medical genetics,genome-scale biology research program,university of helsinki,helsinki, Finland, department of medical genetics,genome-scale biology research program,university of helsinki,helsinki, Finland
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Authors
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