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Finnish Fanconi anemia mutations and hereditary predisposition to breast and prostate cancer.
Clin Genet 2015; 88(1):68-73CG

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+Show Affiliations

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.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.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.BioMediTech and FimLab Laboratories, University of Tampere, Tampere, Finland. Medical Biochemistry and Genetics, Institute of Biomedicine, University of Turku, Turku, Finland.BioMediTech and FimLab Laboratories, University of Tampere, Tampere, Finland.FimLab Laboratories, Laboratory of Clinical Genetics, Tampere, Finland.Pediatric Oncology, Tampere University Hospital, Tampere, Finland.Department of Clinical Genetics, University of Helsinki, Helsinki University Central Hospital, Helsinki, Finland.Department of Clinical Genetics, University of Helsinki, Helsinki University Central Hospital, Helsinki, Finland.Department of Clinical Genetics, University of Helsinki, Helsinki University Central Hospital, Helsinki, Finland.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.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.Department of Pediatrics, Genetics Outpatient Clinic, and Department of Dermatology, Tampere University Hospital, Tampere, Finland.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.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.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.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24989076

Citation

Mantere, T, et al. "Finnish Fanconi Anemia Mutations and Hereditary Predisposition to Breast and Prostate Cancer." Clinical Genetics, vol. 88, no. 1, 2015, pp. 68-73.
Mantere T, Haanpää M, Hanenberg H, et al. Finnish Fanconi anemia mutations and hereditary predisposition to breast and prostate cancer. Clin Genet. 2015;88(1):68-73.
Mantere, T., Haanpää, M., Hanenberg, H., Schleutker, J., Kallioniemi, A., Kähkönen, M., ... Winqvist, R. (2015). Finnish Fanconi anemia mutations and hereditary predisposition to breast and prostate cancer. Clinical Genetics, 88(1), pp. 68-73. doi:10.1111/cge.12447.
Mantere T, et al. Finnish Fanconi Anemia Mutations and Hereditary Predisposition to Breast and Prostate Cancer. Clin Genet. 2015;88(1):68-73. PubMed PMID: 24989076.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Finnish Fanconi anemia mutations and hereditary predisposition to breast and prostate cancer. AU - Mantere,T, AU - Haanpää,M, AU - Hanenberg,H, AU - Schleutker,J, AU - Kallioniemi,A, AU - Kähkönen,M, AU - Parto,K, AU - Avela,K, AU - Aittomäki,K, AU - von Koskull,H, AU - Hartikainen,J M, AU - Kosma,V-M, AU - Laasanen,S-L, AU - Mannermaa,A, AU - Pylkäs,K, AU - Winqvist,R, Y1 - 2014/07/30/ PY - 2014/05/02/received PY - 2014/06/13/revised PY - 2014/06/19/accepted PY - 2014/7/4/entrez PY - 2014/7/6/pubmed PY - 2016/3/5/medline KW - Fanconi anemia KW - breast cancer KW - founder population KW - hereditary susceptibility KW - prostate cancer SP - 68 EP - 73 JF - Clinical genetics JO - Clin. Genet. VL - 88 IS - 1 N2 - 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. SN - 1399-0004 UR - https://www.unboundmedicine.com/medline/citation/24989076/Finnish_Fanconi_anemia_mutations_and_hereditary_predisposition_to_breast_and_prostate_cancer_ L2 - https://doi.org/10.1111/cge.12447 DB - PRIME DP - Unbound Medicine ER -