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Breast cancer risk in BRCA1 and BRCA2 mutation carriers and polyglutamine repeat length in the AIB1 gene
Author(s) -
Hughes David J.,
Ginolhac Sophie M.,
Coupier Isabelle,
Barjhoux Laure,
Gaborieau Valérie,
BressacdePaillerets Brigitte,
Chompret Agnès,
Big YvesJean,
Uhrhammer Nancy,
Lasset Christine,
Giraud Sophie,
Sobol Hagay,
Hardouin Agnès,
Berthet Pascaline,
Peyrat JeanPhilippe,
Fournier Joelle,
Nogues Catherine,
Lidereau Rosette,
Muller Danièle,
Fricker JeanPierre,
Longy Michel,
Toulas Christine,
Guimbaud Rosine,
Yannoukakos Drakoulis,
Mazoyer Sylvie,
Lynch Henry T.,
Lenoir Gilbert M.,
Goldgar David E.,
StoppaLyonnet Dominique,
Sinilnikova Olga M.
Publication year - 2005
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.21176
Subject(s) - breast cancer , penetrance , allele , genetics , germline mutation , biology , cancer , mutation , medicine , cancer research , oncology , gene , phenotype
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. © 2005 Wiley‐Liss, Inc.