title: Finnish Fanconi anemia mutations and hereditary predisposition to breast and prostate cancer.
abstract: Mutations in downstream Fanconi anemia (FA) pathway genes, BRCA2, PALB2, BRIP1 and RAD51C, explain part of the hereditary breast cancer susceptibility, but the contribution of other FA genes has remained questionable. Due to FA's rarity, the finding of recurrent deleterious FA mutations among breast cancer families is challenging. The use of founder populations, such as the Finns, could provide some advantage in this. Here, we have resolved complementation groups and causative mutations of five FA patients, representing the first mutation confirmed FA cases in Finland. These patients belonged to complementation groups FA-A (n = 3), FA-G (n = 1) and FA-I (n = 1). The prevalence of the six FA causing mutations was then studied in breast (n = 1840) and prostate (n = 565) cancer cohorts, and in matched controls (n = 1176 females, n = 469 males). All mutations were recurrent, but no significant association with cancer susceptibility was observed for any: the prevalence of FANCI c.2957_2969del and c.3041G>A mutations was even highest in healthy males (1.7%). This strengthens the exclusive role of downstream genes in cancer predisposition. From a clinical point of view, current results provide fundamental information of the mutations to be tested first in all suspected FA cases in Finland.
authors.affiliation: Department of Clinical Chemistry and Biocenter Oulu, Laboratory of Cancer Genetics and Tumor Biology, University of Oulu, Oulu, Finland.|Laboratory of Cancer Genetics and Tumor Biology, Northern Finland Laboratory Centre NordLab, Oulu, Finland.
authors.forename: T
authors.initials: T
authors.lastname: Mantere
authors.affiliation: Department of Clinical Chemistry and Biocenter Oulu, Laboratory of Cancer Genetics and Tumor Biology, University of Oulu, Oulu, Finland.|Laboratory of Cancer Genetics and Tumor Biology, Northern Finland Laboratory Centre NordLab, Oulu, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Haanpää
authors.affiliation: Department of Pediatrics, Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, IN, USA.|Department of Otorhinolaryngology & Head/Neck Surgery, Heinrich Heine University School of Medicine, Duesseldorf, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Hanenberg
authors.affiliation: BioMediTech and FimLab Laboratories, University of Tampere, Tampere, Finland.|Medical Biochemistry and Genetics, Institute of Biomedicine, University of Turku, Turku, Finland.
authors.forename: J
authors.initials: J
authors.lastname: Schleutker
authors.affiliation: BioMediTech and FimLab Laboratories, University of Tampere, Tampere, Finland.
authors.forename: A
authors.initials: A
authors.lastname: Kallioniemi
authors.affiliation: FimLab Laboratories, Laboratory of Clinical Genetics, Tampere, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Kähkönen
authors.affiliation: Pediatric Oncology, Tampere University Hospital, Tampere, Finland.
authors.forename: K
authors.initials: K
authors.lastname: Parto
authors.affiliation: Department of Clinical Genetics, University of Helsinki, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: K
authors.initials: K
authors.lastname: Avela
authors.affiliation: Department of Clinical Genetics, University of Helsinki, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: K
authors.initials: K
authors.lastname: Aittomäki
authors.affiliation: Department of Clinical Genetics, University of Helsinki, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: H
authors.initials: H
authors.lastname: von Koskull
authors.affiliation: School of Medicine, Institute of Clinical Medicine, Pathology and Forensic Medicine; Cancer Center of Eastern Finland, University of Eastern Finland, Kuopio, Finland.|Imaging Center, Department of Clinical Pathology, Kuopio University Hospital, Kuopio, Finland.
authors.forename: J M
authors.initials: JM
authors.lastname: Hartikainen
authors.affiliation: School of Medicine, Institute of Clinical Medicine, Pathology and Forensic Medicine; Cancer Center of Eastern Finland, University of Eastern Finland, Kuopio, Finland.|Imaging Center, Department of Clinical Pathology, Kuopio University Hospital, Kuopio, Finland.
authors.forename: V-M
authors.initials: VM
authors.lastname: Kosma
authors.affiliation: Department of Pediatrics, Genetics Outpatient Clinic, and Department of Dermatology, Tampere University Hospital, Tampere, Finland.
authors.forename: S-L
authors.initials: SL
authors.lastname: Laasanen
authors.affiliation: School of Medicine, Institute of Clinical Medicine, Pathology and Forensic Medicine; Cancer Center of Eastern Finland, University of Eastern Finland, Kuopio, Finland.|Imaging Center, Department of Clinical Pathology, Kuopio University Hospital, Kuopio, Finland.
authors.forename: A
authors.initials: A
authors.lastname: Mannermaa
authors.affiliation: Department of Clinical Chemistry and Biocenter Oulu, Laboratory of Cancer Genetics and Tumor Biology, University of Oulu, Oulu, Finland.|Laboratory of Cancer Genetics and Tumor Biology, Northern Finland Laboratory Centre NordLab, Oulu, Finland.
authors.forename: K
authors.initials: K
authors.lastname: Pylkäs
authors.affiliation: Department of Clinical Chemistry and Biocenter Oulu, Laboratory of Cancer Genetics and Tumor Biology, University of Oulu, Oulu, Finland.|Laboratory of Cancer Genetics and Tumor Biology, Northern Finland Laboratory Centre NordLab, Oulu, Finland.
authors.forename: R
authors.initials: R
authors.lastname: Winqvist
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D005199:Fanconi Anemia / Q000235:genetics*; D052217:Fanconi Anemia Complementation Group A Protein / Q000235:genetics; D052241:Fanconi Anemia Complementation Group G Protein / Q000235:genetics; D051856:Fanconi Anemia Complementation Group Proteins / Q000235:genetics; D005260:Female; D005387:Finland; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011471:Prostatic Neoplasms / Q000235:genetics*
chemical_list: C498471:FANCA protein, human; C499909:FANCG protein, human; C519921:FANCI protein, human; D052217:Fanconi Anemia Complementation Group A Protein; D052241:Fanconi Anemia Complementation Group G Protein; D051856:Fanconi Anemia Complementation Group Proteins
keywords: Fanconi anemia; breast cancer; founder population; hereditary susceptibility; prostate cancer