title: No MSH6 germline mutations in breast cancer families with colorectal and/or endometrial cancer.
abstract: BACKGROUND
  The genetic background in breast cancer families with colorectal and/or endometrial cancer is mostly unknown. The functional connection between MSH6 and the known breast cancer predisposition gene product BRCA1 suggests that the MSH6 gene may also play a role in breast cancer predisposition.
  
  
  METHODS
  We analysed 38 breast cancer families with colorectal and/or endometrial cancer for germline mutations in MSH6.
  
  
  RESULTS
  No disease associated mutations were detected among the breast cancer families. However, mutation analysis revealed a Glu995STOP mutation in an atypical HNPCC family. The same mutation was found in a patient with both breast and colorectal carcinoma in our previous study, and haplotype analysis confirmed a common ancestral origin. The Glu995STOP mutation was further examined in an extensive series of 245 colorectal and 142 breast carcinoma patients with a family history of breast, colorectal, and/or endometrial carcinoma, and in 268 healthy population controls, but none was found to carry the mutation.
  
  
  CONCLUSIONS
  Our results suggest that MSH6 may not be the underlying gene in breast cancer families with a history of colorectal and/or endometrial cancer. The Glu995STOP founder mutation is not a familial breast cancer predisposition allele and makes only a limited contribution to colorectal cancer burden in Finland.
authors.affiliation: Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: P
authors.initials: P
authors.lastname: Vahteristo
authors.forename: S
authors.initials: S
authors.lastname: Ojala
authors.forename: A
authors.initials: A
authors.lastname: Tamminen
authors.forename: J
authors.initials: J
authors.lastname: Tommiska
authors.forename: H
authors.initials: H
authors.lastname: Sammalkorpi
authors.forename: S
authors.initials: S
authors.lastname: Kiuru-Kuhlefelt
authors.forename: H
authors.initials: H
authors.lastname: Eerola
authors.forename: L A
authors.initials: LA
authors.lastname: Aaltonen
authors.forename: K
authors.initials: K
authors.lastname: Aittomäki
authors.forename: H
authors.initials: H
authors.lastname: Nevanlinna
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics*; D004268:DNA-Binding Proteins; D016889:Endometrial Neoplasms / Q000235:genetics*; D005190:Family / Q000208:ethnology; D005260:Female; D005387:Finland; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D010375:Pedigree
chemical_list: D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein