title: Assessment of an APOBEC3B truncating mutation, c.783delG, in patients with breast cancer.
abstract: APOBEC3B belongs to the family of DNA-editing enzymes. A copy number variant targeting the genomic APOBEC3A-APOBEC3B locus has a significant impact on breast cancer risk, but the relative contribution of APOBEC3B is uncertain. In this study, we investigate a loss-of-function mutation that selectively targets APOBEC3B, for its association with breast cancer risk.
  
  
  
  We performed exome sequencing on genomic DNA samples of 6 Byelorussian patients with familial breast cancer. We then studied through mutation-specific genotyping four hospital-based breast cancer case-control series from Belarus, Russia, Germany, and Iran, respectively, comprising a total of 3070 breast cancer patients and 2878 healthy females. Results were evaluated using fixed-effects meta-analyses.
  
  
  
  Exome sequencing uncovered a frameshift mutation, APOBEC3B*c.783delG, that was recurrent in the study populations. Subsequent genotyping identified this mutation in 23 additional breast cancer cases and 9 healthy female controls, with an adjusted Odds Ratio 2.29 (95% CI 1.04; 5.03, P = 0.04) in the combined analysis. There was an enrichment of the c.783delG mutation in patients with breast cancer diagnosed below 50 years of age (OR 3.22, 95% CI 1.37; 7.56, P = 0.007).
  
  
  
  APOBEC3B*c.783delG showed evidence of modest association with breast cancer and seemed to contribute to earlier onset of the disease. These results may need to be reconciled with proposals to consider APOBEC3B as a possible therapeutic target in breast cancer.
authors.affiliation: Gynaecology Research Unit, Clinics of Obstetrics and Gynaecology, Hannover Medical School, Hannover, Germany.
authors.forename: Hoda
authors.initials: H
authors.lastname: Radmanesh
authors.affiliation: Gynaecology Research Unit, Clinics of Obstetrics and Gynaecology, Hannover Medical School, Hannover, Germany.|Radiation Oncology Research Unit, Hannover Medical School, Hannover, Germany.
authors.forename: Tessa
authors.initials: T
authors.lastname: Spethmann
authors.affiliation: Gynaecology Research Unit, Clinics of Obstetrics and Gynaecology, Hannover Medical School, Hannover, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Enßen
authors.affiliation: Gynaecology Research Unit, Clinics of Obstetrics and Gynaecology, Hannover Medical School, Hannover, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Schürmann
authors.affiliation: Genome Analytics Unit, Helmholtz Center for Infection Research, Brunswick, Germany.
authors.forename: Sabin
authors.initials: S
authors.lastname: Bhuju
authors.affiliation: Genome Analytics Unit, Helmholtz Center for Infection Research, Brunswick, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Geffers
authors.affiliation: N.N. Alexandrov Research Institute of Oncology and Medical Radiology, Minsk, Belarus.
authors.forename: Natalia
authors.initials: N
authors.lastname: Antonenkova
authors.affiliation: Institute of Biochemistry and Genetics, Ufa Science Center, Ufa, Russia.|Department of Genetics and Fundamental Medicine, Bashkir State University, Ufa, Russia.
authors.forename: Elza
authors.initials: E
authors.lastname: Khusnutdinova
authors.affiliation: Medical Genetic Research Center (MGRC), School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.|Molecular Medicine Research Group, Academic Centers for EducationCulture and Research (ACECR), Khorasan Basavi Branch, Mashhad, Iran.|Department of Medical Genetics, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Ariane
authors.initials: A
authors.lastname: Sadr-Nabavi
authors.affiliation: Radiation Oncology Cancer Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Fatemeh Homaei
authors.initials: FH
authors.lastname: Shandiz
authors.affiliation: Gynaecology Research Unit, Clinics of Obstetrics and Gynaecology, Hannover Medical School, Hannover, Germany.
authors.forename: Tjoung-Won
authors.initials: TW
authors.lastname: Park-Simon
authors.affiliation: Gynaecology Research Unit, Clinics of Obstetrics and Gynaecology, Hannover Medical School, Hannover, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Hillemanns
authors.affiliation: Radiation Oncology Research Unit, Hannover Medical School, Hannover, Germany.
authors.forename: Hans
authors.initials: H
authors.lastname: Christiansen
authors.affiliation: Gynaecology Research Unit, Clinics of Obstetrics and Gynaecology, Hannover Medical School, Hannover, Germany.|Radiation Oncology Research Unit, Hannover Medical School, Hannover, Germany.
authors.forename: Natalia
authors.initials: N
authors.lastname: Bogdanova
authors.affiliation: Gynaecology Research Unit, Clinics of Obstetrics and Gynaecology, Hannover Medical School, Hannover, Germany. doerk.thilo@mh-hannover.de.
authors.forename: Thilo
authors.identifier: 0000-0002-9458-0282
authors.initials: T
authors.lastname: Dörk
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000483:Alleles; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D003564:Cytidine Deaminase / Q000235:genetics*; D005260:Female; D018703:Founder Effect; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D015778:Minor Histocompatibility Antigens / Q000235:genetics*; D016017:Odds Ratio; D017384:Sequence Deletion; D000073359:Exome Sequencing
chemical_list: D015778:Minor Histocompatibility Antigens; C495794:APOBEC3B protein, human; D003564:Cytidine Deaminase
keywords: Breast carcinoma; DNA editing; Founder mutation; Genetic susceptibility