Breast cancer risk in BRCA1 and BRCA2 mutation carriers and polyglutamine repeat length in the AIB1 gene
Year: 2005
Type: article
Study design: Observational Study
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.
Source: International Journal of Cancer
DOI: 10.1002/ijc.21176
Authors: David J. Hughes, Sophie M. Ginolhac, Isabelle Coupier, Laure Barjhoux, Valérie Gaborieau, Brigitte Bressac‐de‐Paillerets, Agnès Chompret, Yves‐Jean Bignon, Nancy Uhrhammer, Christine Lasset, Sophie Giraud, Hagay Sobol, Agnès Hardouin, Pascaline Berthet, Jean‐Philippe Peyrat, Joelle Fournier, Catherine Nogues, Rosette Lidereau, Danièle Muller, Jean‐Pierre Fricker, Michel Longy, Christine Toulas, Rosine Guimbaud, Drakoulis Yannoukakos, Sylvie Mazoyer, Henry T. Lynch, Gilbert M. Lenoir, David E. Goldgar, Dominique Stoppa‐Lyonnet, Olga M. Sinilnikova
Institutions: Centre international de recherche sur le cancer, Inserm, Institut Curie, Institut Gustave Roussy, Centre Jean Perrin, Centre Léon Bérard, Hospices Civils de Lyon, Institut Paoli-Calmettes, Centre François Baclesse, Centre Oscar Lambret, Hôpital René Huguenin, Institut Strauss, Institut Bergonié, Institut Claudius Regaud, National Centre of Scientific Research "Demokritos", Lyon 1 Université, Centre National de la Recherche Scientifique, Creighton University
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W2078837019