title: Association of the rs1346044 Polymorphism of the Werner Syndrome Gene RECQL2 with Increased Risk and Premature Onset of Breast Cancer.
abstract: Like other RECQ helicases, WRN/RECQL2 plays a crucial role in DNA replication and the maintenance of genome stability. Inactivating mutations in RECQL2 lead to Werner syndrome, a rare autosomal disease associated with premature aging and an increased susceptibility to multiple cancer types. We analyzed the association of two coding single-nucleotide polymorphisms in WRN, Cys1367Arg (rs1346044), and Arg834Cys (rs3087425), with the risk, age at onset, and clinical subclasses of breast cancer in a hospital-based case-control study of an Austrian population of 272 breast cancer patients and 254 controls. Here we report that the rare homozygous CC genotype of rs1346044 was associated with an approximately two-fold elevated breast cancer risk. Moreover, patients with the CC genotype exhibited a significantly increased risk of developing breast cancer under the age of 55 in both recessive and log-additive genetic models. CC patients developed breast cancer at a mean age of 55.2 ± 13.3 years and TT patients at 60.2 ± 14.7 years. Consistently, the risk of breast cancer was increased in pre-menopausal patients in the recessive model. These findings suggest that the CC genotype of WRN rs1346044 may contribute to an increased risk and a premature onset of breast cancer.
authors.affiliation: Laboratory for Molecular Cellular Biology, Center for Anatomy and Cell Biology, Medical University of Vienna, A-1090 Vienna, Austria. karin.zins@meduniwien.ac.at.
authors.forename: Karin
authors.initials: K
authors.lastname: Zins
authors.affiliation: Department of Obstetrics and Gynecology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria. barbara.frech@gmx.net.
authors.forename: Barbara
authors.initials: B
authors.lastname: Frech
authors.affiliation: Department of Obstetrics and Gynecology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria. eva.taubenschuss@gmx.at.
authors.forename: Eva
authors.initials: E
authors.lastname: Taubenschuss
authors.affiliation: Department of Obstetrics and Gynecology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria. christian.schneeberger@meduniwien.ac.at.
authors.forename: Christian
authors.initials: C
authors.lastname: Schneeberger
authors.affiliation: Laboratory for Molecular Cellular Biology, Center for Anatomy and Cell Biology, Medical University of Vienna, A-1090 Vienna, Austria. dietmar.abraham@meduniwien.ac.at.|Comprehensive Cancer Center (CCC), Medical University of Vienna, A-1090 Vienna, Austria. dietmar.abraham@meduniwien.ac.at.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Abraham
authors.affiliation: Department of Obstetrics and Gynecology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria. martin.schreiber@meduniwien.ac.at.|Comprehensive Cancer Center (CCC), Medical University of Vienna, A-1090 Vienna, Austria. martin.schreiber@meduniwien.ac.at.
authors.forename: Martin
authors.initials: M
authors.lastname: Schreiber
mesh_terms: D017668:Age of Onset; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D005090:Exodeoxyribonucleases / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D053484:RecQ Helicases / Q000235:genetics*; D012306:Risk; D014898:Werner Syndrome / Q000235:genetics; D000071657:Werner Syndrome Helicase
chemical_list: D005090:Exodeoxyribonucleases; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase
keywords: RECQL2; WRN; Werner syndrome; breast cancer; rs1346044; rs3087425; single nucleotide polymorphism (SNP)