Hereditary nonpolyposis colon cancer: Analysis of linkage to 2p 15-16 places the COCA1 locus telomeric to D2S123 and reveals genetic heterogeneity in seven Canadian families
- Memorial Univ. of Newfoundland, St. John's (Canada)
- Montreal General Hospital, Montreal (Canada) Royal Victoria Hospital, Montreal (Canada)
- Hopital St-Francois d'Assise, Quebec City (Canada)
- Grenfell Regional Health Services, St. Anthony, Newfoundland (Canada)
- Royal Victoria Hospital, Montreal (Canada); and others
Hereditary nonpolyposis colon cancer (HNPCC) is an autosomal dominant trait responsible for approximately 6% of colorectal cancers. Linkage of the HNPCC trait to the D2S123 locus on 2p 15-16 has previously been reported in two families. This HNPCC locus is now designated [open quotes]COCA1[close quotes]. The authors have tested seven Canadian HNPCC families, who have a variety of clinical presentations, for linkage to a panel of microsatellite polymorphisms in the vicinity of D2S123. One family was clearly linked to the COCA1 locus (LOD = 4.21), and a second family is likely to be linked (LOD = 0.92). In three families linkage was excluded. In the remaining two families the data were inconclusive. In the linked family, individuals with cancer of the endometrium or ureter share a common haplotype with 12 family members with colorectal cancer. This supports the suspected association between these extracolonic neoplasms and the HNPCC syndrome. In addition, five of the six individuals with adenomatous polyps (but no colorectal cancer) have the same haplotype as the affected individuals, while the sixth carries a recombination. One individual with colorectal cancer carries a recombination that places the COCA1 locus telomeric to D2S123. This study localizes the COCA1 gene to an 8-cM region that is consistent with the location of the hMSH2 gene. The authors also confirm that families presently classified as HNPCC are genetically heterogeneous. 36 refs., 4 figs., 2 tabs.
- OSTI ID:
- 7159780
- Journal Information:
- American Journal of Human Genetics; (United States), Vol. 54:6; ISSN 0002-9297
- Country of Publication:
- United States
- Language:
- English
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