title: Inbreeding and homozygosity in breast cancer survival.
abstract: Genome-wide association studies (GWASs) help to understand the effects of single nucleotide polymorphisms (SNPs) on breast cancer (BC) progression and survival. We performed multiple analyses on data from a previously conducted GWAS for the influence of individual SNPs, runs of homozygosity (ROHs) and inbreeding on BC survival. (I.) The association of individual SNPs indicated no differences in the proportions of homozygous individuals among short-time survivors (STSs) and long-time survivors (LTSs). (II.) The analysis revealed differences among the populations for the number of ROHs per person and the total and average length of ROHs per person and among LTSs and STSs for the number of ROHs per person. (III.) Common ROHs at particular genomic positions were nominally more frequent among LTSs than in STSs. Common ROHs showed significant evidence for natural selection (iHS, Tajima's D, Fay-Wu's H). Most regions could be linked to genes related to BC progression or treatment. (IV.) Results were supported by a higher level of inbreeding among LTSs. Our results showed that an increased level of homozygosity may result in a preference of individuals during BC treatment. Although common ROHs were short, variants within ROHs might favor survival of BC and may function in a recessive manner.
authors.affiliation: Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Hauke
authors.initials: H
authors.lastname: Thomsen
authors.affiliation: Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Miguel Inacio da Silva
authors.initials: MI
authors.lastname: Filho
authors.affiliation: Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Woltmann
authors.affiliation: Department of Radiation Sciences &Oncology, Umeå University, Umeå, Sweden.
authors.forename: Robert
authors.initials: R
authors.lastname: Johansson
authors.affiliation: Cancer Research Laboratory, Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
authors.forename: Jorunn E
authors.initials: JE
authors.lastname: Eyfjörd
authors.affiliation: Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Ute
authors.initials: U
authors.lastname: Hamann
authors.affiliation: The Malmö Diet and Cancer Study, Lund University, Malmö, Sweden.|Department of Plastic Surgery, Skåne University Hospital, Malmö, Lund University, Malmö, Sweden.
authors.forename: Jonas
authors.initials: J
authors.lastname: Manjer
authors.affiliation: Department of Public Health and Clinical Medicine/Nutritional Research, Umeå University, Umeå, Sweden.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Enquist-Olsson
authors.affiliation: Department of Radiation Sciences &Oncology, Umeå University, Umeå, Sweden.|Cancer Center Stockholm Gotland, Stockholm, Sweden.
authors.forename: Roger
authors.initials: R
authors.lastname: Henriksson
authors.affiliation: Institute of Human Genetics, Department of Genomics, University of Bonn, Bonn, Germany.|Division of Medical Genetics and Department of Biomedicine, University of Basel, Basel, Switzerland.
authors.forename: Stefan
authors.initials: S
authors.lastname: Herms
authors.affiliation: Institute of Human Genetics, Department of Genomics, University of Bonn, Bonn, Germany.|Division of Medical Genetics and Department of Biomedicine, University of Basel, Basel, Switzerland.
authors.forename: Per
authors.initials: P
authors.lastname: Hoffmann
authors.affiliation: Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Bowang
authors.initials: B
authors.lastname: Chen
authors.affiliation: Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Huhn
authors.affiliation: Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.|Center for Primary Health Care Research, Clinical Research Center, Lund University, Malmö, Sweden.
authors.forename: Kari
authors.initials: K
authors.lastname: Hemminki
authors.affiliation: Department of Radiation Sciences &Oncology, Umeå University, Umeå, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Lenner
authors.affiliation: Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.|Center for Primary Health Care Research, Clinical Research Center, Lund University, Malmö, Sweden.
authors.forename: Asta
authors.initials: A
authors.lastname: Försti
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality*; D003241:Consanguinity; D005260:Female; D020022:Genetic Predisposition to Disease; D005828:Genetics, Population; D055106:Genome-Wide Association Study; D006801:Humans; D007178:Inbreeding; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012641:Selection, Genetic