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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Breast cancer risk in BRCA1 and BRCA2 mutation carriers and polyglutamine repeat length in the AIB1 gene.

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.[1]


  1. Breast cancer risk in BRCA1 and BRCA2 mutation carriers and polyglutamine repeat length in the AIB1 gene. Hughes, D.J., Ginolhac, S.M., Coupier, I., Barjhoux, L., Gaborieau, V., Bressac-de-Paillerets, B., Chompret, A., Bignon, Y.J., Uhrhammer, N., Lasset, C., Giraud, S., Sobol, H., Hardouin, A., Berthet, P., Peyrat, J.P., Fournier, J., Nogues, C., Lidereau, R., Muller, D., Fricker, J.P., Longy, M., Toulas, C., Guimbaud, R., Yannoukakos, D., Mazoyer, S., Lynch, H.T., Lenoir, G.M., Goldgar, D.E., Stoppa-Lyonnet, D., Sinilnikova, O.M. Int. J. Cancer (2005) [Pubmed]
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