title: c-MYC Asn11Ser is associated with increased risk for familial breast cancer.
abstract: c-MYC is a multifaceted protein that regulates cell proliferation, differentiation and apoptosis. Its crucial role in diverse cancers has been demonstrated in several studies. Here, we analysed the influence of the rare c-MYC Asn11Ser polymorphism on familial breast cancer risk by performing a case-control study with a Polish (cases n = 349; controls n = 441) and a German (cases n = 356; controls n = 655) study population. All cases have been tested negative for mutations in the BRCA1 and BRCA2 genes. A joint analysis of the Polish and the German study population revealed a 54% increased risk for breast cancer associated with the heterozygous Asn11Ser variant (OR = 1.54, 95% CI 1.05-2.26, p = 0.028). The breast cancer risk associated with this genotype increases above the age of 50 years (OR = 2.24, 95% CI 1.20-4.21, p = 0.012). The wild-type amino acid Asn of this polymorphism is located in the N-terminal MYC transactivation domain and is highly conserved not only among most diverse species but also in the N-MYC homologue. Due to the pivotal role of c-MYC in diverse tumours, this variant might affect the genetic susceptibility of other cancers as well.
authors.affiliation: Division of Molecular Genetic Epidemiology, German Cancer Research Centre (DKFZ), Heidelberg.
authors.forename: Michael
authors.initials: M
authors.lastname: Wirtenberger
authors.forename: Kari
authors.initials: K
authors.lastname: Hemminki
authors.forename: Asta
authors.initials: A
authors.lastname: Försti
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Klaes
authors.forename: Rita K
authors.initials: RK
authors.lastname: Schmutzler
authors.forename: Ewa
authors.initials: E
authors.lastname: Grzybowska
authors.forename: Justo L
authors.initials: JL
authors.lastname: Bermejo
authors.forename: Barbara
authors.initials: B
authors.lastname: Wappenschmidt
authors.forename: Peter
authors.initials: P
authors.lastname: Bugert
authors.forename: Dorota
authors.initials: D
authors.lastname: Butkiewicz
authors.forename: Jolanta
authors.initials: J
authors.lastname: Pamula
authors.forename: Wioletta
authors.initials: W
authors.lastname: Pekala
authors.forename: Helena
authors.initials: H
authors.lastname: Zientek
authors.forename: Claus R
authors.initials: CR
authors.lastname: Bartram
authors.forename: Barbara
authors.initials: B
authors.lastname: Burwinkel
mesh_terms: D000595:Amino Acid Sequence; D001216:Asparagine / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide; D016271:Proto-Oncogene Proteins c-myc / Q000737:chemistry / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D012694:Serine / Q000235:genetics*
chemical_list: D016271:Proto-Oncogene Proteins c-myc; D012694:Serine; D001216:Asparagine