title: High prevalence of BRCA1 stop mutation c.4183C>T in the Tyrolean population: implications for genetic testing.
abstract: Screening for founder mutations in BRCA1 and BRCA2 has been discussed as a cost-effective testing strategy in certain populations. In this study, comprehensive BRCA1 and BRCA2 testing was performed in a routine diagnostic setting. The prevalence of the BRCA1 stop mutation c.4183C>T, p.(Gln1395Ter), was determined in unselected breast and ovarian cancer patients from different regions in the Tyrol. Cancer registry data were used to evaluate the impact of this mutation on regional cancer incidence. The mutation c.4183C>T was detected in 30.4% of hereditary BRCA1-associated breast and ovarian cancer patients in our cohort. It was also identified in 4.1% of unselected (26% of unselected triple negative) Tyrolean breast cancer patients and 6.8% of unselected ovarian cancer patients from the Lower Inn Valley (LIV) region. Cancer incidences showed a region-specific increase in age-stratified breast and ovarian cancer risk with standardized incidence ratios of 1.23 and 2.13, respectively. We, thus, report a Tyrolean BRCA1 founder mutation that correlates to a local increase in the breast and ovarian cancer risks. On the basis of its high prevalence, we suggest that targeted genetic analysis should be offered to all women with breast or ovarian cancer and ancestry from the LIV region.
authors.affiliation: Division of Human Genetics, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Laura
authors.initials: L
authors.lastname: Pölsler
authors.affiliation: Department of Obstetrics and Gynaecology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Heidi
authors.initials: H
authors.lastname: Fiegl
authors.affiliation: Division of Human Genetics, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Katharina
authors.initials: K
authors.lastname: Wimmer
authors.affiliation: Department of Clinical Epidemiology of the Tyrolean State Hospitals Ltd., Cancer Registry of Tyrol, Austria.|Department of Public Health and HTA, UMIT-Private University of Health Sciences, Medical Informatics and Technology, Hall in Tirol, Austria.
authors.forename: Willi
authors.initials: W
authors.lastname: Oberaigner
authors.affiliation: Division of Human Genetics, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Albert
authors.initials: A
authors.lastname: Amberger
authors.affiliation: Division of Human Genetics, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Pia
authors.initials: P
authors.lastname: Traunfellner
authors.affiliation: Division of Human Genetics, Medical University of Innsbruck, Innsbruck, Austria.|Research Programme for Receptor Biochemistry and Tumour Metabolism, Paracelsus Medical University, Salzburg, Austria.
authors.forename: Raphael J
authors.initials: RJ
authors.lastname: Morscher
authors.affiliation: Division of Human Genetics, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Weber
authors.affiliation: Division of Human Genetics, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Christine
authors.initials: C
authors.lastname: Fauth
authors.affiliation: Division of Human Genetics, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Annekatrin
authors.initials: A
authors.lastname: Wernstedt
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Barbara
authors.initials: B
authors.lastname: Sperner-Unterweger
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Anne
authors.initials: A
authors.lastname: Oberguggenberger
authors.affiliation: Department of Obstetrics and Gynaecology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Hubalek
authors.affiliation: Department of Obstetrics and Gynaecology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Marth
authors.affiliation: Division of Human Genetics, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Johannes
authors.initials: J
authors.lastname: Zschocke
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D018388:Codon, Terminator / Q000235:genetics; D005260:Female; D018703:Founder Effect; D005820:Genetic Testing; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D019313:BRCA1 Protein; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D018388:Codon, Terminator