title: Genome-wide scanning for linkage in Finnish breast cancer families.
abstract: Only a proportion of breast cancer families has germline mutations in the BRCA1 or BRCA2 genes, suggesting the presence of additional susceptibility genes. Finding such genes by linkage analysis has turned out to be difficult due to the genetic heterogeneity of the disease, phenocopies and incomplete penetrance of the mutations. Isolated populations may be helpful in reducing the level of genetic heterogeneity and in providing useful starting points for further genetic analyses. Here, we report results from a genome-wide linkage analysis of 14 high-risk breast cancer families from Finland. These families tested negative for BRCA1 and BRCA2 germline mutations and showed no linkage to the 13q21 region, recently proposed as an additional susceptibility locus. Suggestive linkage was seen at marker D2S364 (2q32) with a parametric two-point LOD score of 1.61 (theta=0), and an LOD score of 2.49 in nonparametric analyses. Additional genotyping of a 40 cM chromosomal region surrounding the region of interest yielded a maximum parametric two-point LOD score of 1.80 (theta=0) at D2S2262 and a nonparametric LOD score of 3.11 at an adjacent novel marker 11291M1 in BAC RP11-67G7. A nonparametric multipoint LOD score of 3.20 was seen at 11291M1 under the assumption of dominant inheritance. While not providing proof of linkage considering the small number of families and large number of laboratory and statistical analyses performed, these results warrant further studies of the 2q32 chromosomal region as a candidate breast cancer susceptibility locus. Both linkage and association studies are likely to be useful, particularly in other isolated populations.
authors.affiliation: Cancer Genetics Branch, NHGRI, NIH, Helsinki University, Central Hospital, Helsinki, Finland.
authors.forename: Pia
authors.initials: P
authors.lastname: Huusko
authors.forename: Suh-Hang Hank
authors.initials: SH
authors.lastname: Juo
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Gillanders
authors.forename: Laura
authors.initials: L
authors.lastname: Sarantaus
authors.forename: Tommi
authors.initials: T
authors.lastname: Kainu
authors.forename: Pia
authors.initials: P
authors.lastname: Vahteristo
authors.forename: Minna
authors.initials: M
authors.lastname: Allinen
authors.forename: MaryPat
authors.initials: M
authors.lastname: Jones
authors.forename: Katrin
authors.initials: K
authors.lastname: Rapakko
authors.forename: Hannaleena
authors.initials: H
authors.lastname: Eerola
authors.forename: Carol
authors.initials: C
authors.lastname: Markey
authors.forename: Paula
authors.initials: P
authors.lastname: Vehmanen
authors.forename: Derek
authors.initials: D
authors.lastname: Gildea
authors.forename: Diane
authors.initials: D
authors.lastname: Freas-Lutz
authors.forename: Carl
authors.initials: C
authors.lastname: Blomqvist
authors.forename: Jaakko
authors.initials: J
authors.lastname: Leisti
authors.forename: Guillermo
authors.initials: G
authors.lastname: Blanco
authors.forename: Ulla
authors.initials: U
authors.lastname: Puistola
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Trent
authors.forename: Joan
authors.initials: J
authors.lastname: Bailey-Wilson
authors.forename: Robert
authors.initials: R
authors.lastname: Winqvist
authors.forename: Heli
authors.initials: H
authors.lastname: Nevanlinna
authors.forename: Olli-P
authors.initials: OP
authors.lastname: Kallioniemi
mesh_terms: D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics*; D002874:Chromosome Mapping; D017931:DNA Primers; D005387:Finland; D008040:Genetic Linkage; D006801:Humans
chemical_list: D017931:DNA Primers