title: Breast cancer risk in BRCA1 and BRCA2 mutation carriers and polyglutamine repeat length in the AIB1 gene.
abstract: Marked variation in phenotypic expression among BRCA1 and BRCA2 mutation carriers may be partly explained by modifier genes that influence mutation penetrance. Variation in CAG/CAA repeat lengths coding for stretches of glutamines in the C-terminus of the AIB1 protein (amplified in breast cancer 1, a steroid receptor coactivator) has been proposed to modify the breast cancer risk in women carrying germline BRCA1 mutations. We genotyped the AIB1 repeat length polymorphism from the genomic DNA of a group of 851 BRCA1 and 324 BRCA2 female germline mutation carriers to estimate an association with breast cancer risk modification. Hazard ratios (HR) were calculated using a Cox proportional hazards model. For BRCA1 and BRCA2 mutation carriers, analyzed separately and together, we found that women who carried alleles with 28 or more polyglutamine repeats had no increased risk of breast cancer compared to those who carried alleles with fewer repeats (HR for BRCA1/2 carriers = 0.88, 95% CI [confidence interval] = 0.75-1.04). Analyzing average repeat lengths as a continuous variable showed no excess risk of breast cancer (BC) in BRCA1 or BRCA2 mutation carriers (HR for average repeat length in BRCA1/2 carriers = 1.01, 95% CI = 0.92-1.11). These results strongly suggest that contrary to previous studies, there is no significant effect of AIB1 genetic variation on BC risk in BRCA1 mutation carriers and provide an indication that there is also no strong risk modification in BRCA2 carriers.
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: David J
authors.initials: DJ
authors.lastname: Hughes
authors.forename: Sophie M
authors.initials: SM
authors.lastname: Ginolhac
authors.forename: Isabelle
authors.initials: I
authors.lastname: Coupier
authors.forename: Laure
authors.initials: L
authors.lastname: Barjhoux
authors.forename: Valérie
authors.initials: V
authors.lastname: Gaborieau
authors.forename: Brigitte
authors.initials: B
authors.lastname: Bressac-de-Paillerets
authors.forename: Agnès
authors.initials: A
authors.lastname: Chompret
authors.forename: Yves-Jean
authors.initials: YJ
authors.lastname: Bignon
authors.forename: Nancy
authors.initials: N
authors.lastname: Uhrhammer
authors.forename: Christine
authors.initials: C
authors.lastname: Lasset
authors.forename: Sophie
authors.initials: S
authors.lastname: Giraud
authors.forename: Hagay
authors.initials: H
authors.lastname: Sobol
authors.forename: Agnès
authors.initials: A
authors.lastname: Hardouin
authors.forename: Pascaline
authors.initials: P
authors.lastname: Berthet
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Peyrat
authors.forename: Joelle
authors.initials: J
authors.lastname: Fournier
authors.forename: Catherine
authors.initials: C
authors.lastname: Nogues
authors.forename: Rosette
authors.initials: R
authors.lastname: Lidereau
authors.forename: Danièle
authors.initials: D
authors.lastname: Muller
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Fricker
authors.forename: Michel
authors.initials: M
authors.lastname: Longy
authors.forename: Christine
authors.initials: C
authors.lastname: Toulas
authors.forename: Rosine
authors.initials: R
authors.lastname: Guimbaud
authors.forename: Drakoulis
authors.initials: D
authors.lastname: Yannoukakos
authors.forename: Sylvie
authors.initials: S
authors.lastname: Mazoyer
authors.forename: Henry T
authors.initials: HT
authors.lastname: Lynch
authors.forename: Gilbert M
authors.initials: GM
authors.lastname: Lenoir
authors.forename: David E
authors.initials: DE
authors.lastname: Goldgar
authors.forename: Dominique
authors.initials: D
authors.lastname: Stoppa-Lyonnet
authors.forename: Olga M
authors.initials: OM
authors.lastname: Sinilnikova
mesh_terms: D000123:Acetyltransferases / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006580:Genetic Carrier Screening; D014644:Genetic Variation; D018095:Germ-Line Mutation; D051548:Histone Acetyltransferases; D006801:Humans; D008875:Middle Aged; D056921:Nuclear Receptor Coactivator 3; D015513:Oncogene Proteins / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000453:epidemiology / Q000235:genetics; D010455:Peptides / Q000235:genetics*; D012306:Risk; D015534:Trans-Activators / Q000235:genetics*; D018911:Trinucleotide Repeats
chemical_list: D015513:Oncogene Proteins; D010455:Peptides; D015534:Trans-Activators; C097188:polyglutamine; D000123:Acetyltransferases; D051548:Histone Acetyltransferases; C538866:NCOA3 protein, human; D056921:Nuclear Receptor Coactivator 3