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Article: Frequent microsatellite instability and mismatch repair gene mutations in young Chinese patients with colorectal cancer

TitleFrequent microsatellite instability and mismatch repair gene mutations in young Chinese patients with colorectal cancer
Authors
Issue Date1999
PublisherOxford University Press. The Journal's web site is located at http://jncicancerspectrum.oxfordjournals.org/
Citation
Journal Of The National Cancer Institute, 1999, v. 91 n. 14, p. 1221-1226 How to Cite?
AbstractBackground: The incidence of colorectal cancer in persons under 46 years of age is substantially higher in Hong Kong than in Scotland and many other countries. Consequently, we examined whether there is a hereditary predisposition for colorectal cancer in this Southern Chinese population. Methods: We investigated the incidence of microsatellite instability (MSI) at 10 DNA sites in 117 colorectal cancer specimens from Chinese patients of various ages. Those tumors with new alleles at 40% or more of the sites investigated were identified as highly unstable MSI (MSI-H). In young patients, we also searched for germline mutations in three mismatch repair genes (hMSH2, hMLH1, and hMSH6). Results: The incidence of MSI-H varied statistically significantly with age, being observed in more than 60% of those younger than age 31 years at diagnosis and in fewer than 15% of those age 46 years or older. In 15 patients (<46 years old) whose colorectal cancers showed MSI-H, eight possessed germline mutations in either hMSH2 or hMLH1. When mutations in hMSH6 were included, more than 80% of Chinese colorectal cancer patients younger than 31 years had germline mutations in mismatch repair genes. We found a novel germline missense mutation in hMSH6 in a 29-year-old man whose tumor showed no MSI. Two patients had a 4-base- pair insertion in exon 10 causing a truncated protein; this insertion is a common polymorphism with a population allele frequency in Chinese of 5.6%. Conclusions: Our results indicate that germline mutations in mismatch repair genes contribute substantially to the pathogenesis and high incidence of colorectal cancer in young Hong Kong Chinese. However, because young Chinese and Caucasians show similar proportions of colorectal cancers with MSI-H, despite the higher incidence in the former, additional factors may underlie the high susceptibility of young Chinese to colorectal cancer.
Persistent Identifierhttp://hdl.handle.net/10722/88411
ISSN
2015 Impact Factor: 11.37
2015 SCImago Journal Rankings: 6.192
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorChan, TLen_HK
dc.contributor.authorYuen, STen_HK
dc.contributor.authorChung, LPen_HK
dc.contributor.authorHo, JWCen_HK
dc.contributor.authorKwan, KYMen_HK
dc.contributor.authorChan, ASYen_HK
dc.contributor.authorHo, JCYen_HK
dc.contributor.authorLeung, SYen_HK
dc.contributor.authorWyllie, AHen_HK
dc.date.accessioned2010-09-06T09:43:01Z-
dc.date.available2010-09-06T09:43:01Z-
dc.date.issued1999en_HK
dc.identifier.citationJournal Of The National Cancer Institute, 1999, v. 91 n. 14, p. 1221-1226en_HK
dc.identifier.issn0027-8874en_HK
dc.identifier.urihttp://hdl.handle.net/10722/88411-
dc.description.abstractBackground: The incidence of colorectal cancer in persons under 46 years of age is substantially higher in Hong Kong than in Scotland and many other countries. Consequently, we examined whether there is a hereditary predisposition for colorectal cancer in this Southern Chinese population. Methods: We investigated the incidence of microsatellite instability (MSI) at 10 DNA sites in 117 colorectal cancer specimens from Chinese patients of various ages. Those tumors with new alleles at 40% or more of the sites investigated were identified as highly unstable MSI (MSI-H). In young patients, we also searched for germline mutations in three mismatch repair genes (hMSH2, hMLH1, and hMSH6). Results: The incidence of MSI-H varied statistically significantly with age, being observed in more than 60% of those younger than age 31 years at diagnosis and in fewer than 15% of those age 46 years or older. In 15 patients (<46 years old) whose colorectal cancers showed MSI-H, eight possessed germline mutations in either hMSH2 or hMLH1. When mutations in hMSH6 were included, more than 80% of Chinese colorectal cancer patients younger than 31 years had germline mutations in mismatch repair genes. We found a novel germline missense mutation in hMSH6 in a 29-year-old man whose tumor showed no MSI. Two patients had a 4-base- pair insertion in exon 10 causing a truncated protein; this insertion is a common polymorphism with a population allele frequency in Chinese of 5.6%. Conclusions: Our results indicate that germline mutations in mismatch repair genes contribute substantially to the pathogenesis and high incidence of colorectal cancer in young Hong Kong Chinese. However, because young Chinese and Caucasians show similar proportions of colorectal cancers with MSI-H, despite the higher incidence in the former, additional factors may underlie the high susceptibility of young Chinese to colorectal cancer.en_HK
dc.languageengen_HK
dc.publisherOxford University Press. The Journal's web site is located at http://jncicancerspectrum.oxfordjournals.org/en_HK
dc.relation.ispartofJournal of the National Cancer Instituteen_HK
dc.rightsJournal of the National Cancer Institute (Print). Copyright © Oxford University Press.en_HK
dc.subject.meshAdenocarcinoma - ethnology - geneticsen_HK
dc.subject.meshAdulten_HK
dc.subject.meshAge Factorsen_HK
dc.subject.meshAgeden_HK
dc.subject.meshAsian Continental Ancestry Group - geneticsen_HK
dc.subject.meshChinaen_HK
dc.subject.meshColorectal Neoplasms - ethnology - geneticsen_HK
dc.subject.meshDNA Repair - geneticsen_HK
dc.subject.meshEuropean Continental Ancestry Group - geneticsen_HK
dc.subject.meshFemaleen_HK
dc.subject.meshGerm-Line Mutationen_HK
dc.subject.meshHong Kongen_HK
dc.subject.meshHumansen_HK
dc.subject.meshMaleen_HK
dc.subject.meshMicrosatellite Repeats - geneticsen_HK
dc.subject.meshMiddle Ageden_HK
dc.subject.meshPolymorphism, Single-Stranded Conformationalen_HK
dc.titleFrequent microsatellite instability and mismatch repair gene mutations in young Chinese patients with colorectal canceren_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0027-8874&volume=91&spage=1221&epage=1226&date=1999&atitle=Frequent+microsatellite+instability+and+mismatch+repair+gene+mutations+in+young+Chinese+patients+with+colorectal+canceren_HK
dc.identifier.emailChan, TL: tlchan@hku.hken_HK
dc.identifier.emailChung, LP: lpchung@hkucc.hku.hken_HK
dc.identifier.emailLeung, SY: suetyi@hku.hken_HK
dc.identifier.authorityChan, TL=rp00418en_HK
dc.identifier.authorityChung, LP=rp00249en_HK
dc.identifier.authorityLeung, SY=rp00359en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.pmid10413423-
dc.identifier.scopuseid_2-s2.0-0001298972en_HK
dc.identifier.hkuros47263en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0001298972&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume91en_HK
dc.identifier.issue14en_HK
dc.identifier.spage1221en_HK
dc.identifier.epage1226en_HK
dc.identifier.isiWOS:000081946700012-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridChan, TL=7402687537en_HK
dc.identifier.scopusauthoridYuen, ST=8323342200en_HK
dc.identifier.scopusauthoridChung, LP=24315879100en_HK
dc.identifier.scopusauthoridHo, JWC=7402649983en_HK
dc.identifier.scopusauthoridKwan, KYM=36937078000en_HK
dc.identifier.scopusauthoridChan, ASY=7403168075en_HK
dc.identifier.scopusauthoridHo, JCY=7402650284en_HK
dc.identifier.scopusauthoridLeung, SY=7202044886en_HK
dc.identifier.scopusauthoridWyllie, AH=35474548100en_HK

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