title: Polymorphisms in BRCA2 resulting in aberrant codon-usage and their analysis on familial breast cancer risk.
abstract: Mutations in BRCA1 and BRCA2 are associated with increased breast cancer risk. While numerous non-synonymous SNPs in BRCA1/2 have been investigated for breast cancer risk, the impact of synonymous SNPs has not been studied so far. Recently, it has been reported that synonymous SNPs leading to an aberration from the preferred codon-usage can have functional effects and consequently be associated with disease. This motivated us to search for SNPs with the tendency to differential codon-usage in BRCA1/BRCA2. Based on defined criteria, two codon-usage-changing variants, Ser455Ser (1365A > G) and Ser2414Ser (7242A > G), were detected in BRCA2, whereas no such variant could be identified in BRCA1. We investigated the impact of these variants on breast cancer risk in a large case-control study. However, both SNPs, BRCA2 Ser2414Ser (7242A > G) and Ser455Ser (1365A > G), showed no association with breast cancer risk. This indicates that these codon-usage-changing SNPs have no major impact on familial breast cancer risk.
authors.affiliation: Helmholtz-University Group Molecular Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120, Heidelberg, Germany. r.yang@dkfz.de
authors.forename: Rongxi
authors.initials: R
authors.lastname: Yang
authors.forename: Bowang
authors.initials: B
authors.lastname: Chen
authors.forename: Kari
authors.initials: K
authors.lastname: Hemminki
authors.forename: Barbara
authors.initials: B
authors.lastname: Wappenschmidt
authors.forename: Christoph
authors.initials: C
authors.lastname: Engel
authors.forename: Christian
authors.initials: C
authors.lastname: Sutter
authors.forename: Nina
authors.initials: N
authors.lastname: Ditsch
authors.forename: Bernhard H F
authors.initials: BH
authors.lastname: Weber
authors.forename: Dieter
authors.initials: D
authors.lastname: Niederacher
authors.forename: Norbert
authors.initials: N
authors.lastname: Arnold
authors.forename: Alfons
authors.initials: A
authors.lastname: Meindl
authors.forename: Claus R
authors.initials: CR
authors.lastname: Bartram
authors.forename: Rita K
authors.initials: RK
authors.lastname: Schmutzler
authors.forename: Barbara
authors.initials: B
authors.lastname: Burwinkel
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D003062:Codon; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
chemical_list: D003062:Codon