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

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 FrickerMichel Longy, Christine Toulas, Rosine Guimbaud, Drakoulis Yannoukakos, Sylvie Mazoyer, Henry T. Lynch, Gilbert M. Lenoir, David E. Goldgar, Dominique Stoppa-Lyonnet, Olga M. Sinilnikova

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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.

Original languageEnglish
Pages (from-to)230-233
Number of pages4
JournalInternational Journal of Cancer
Volume117
Issue number2
DOIs
StatePublished - Nov 1 2005

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Breast Neoplasms
Mutation
Genes
Germ-Line Mutation
Nuclear Receptor Coactivator 3
Alleles
Modifier Genes
Confidence Intervals
Penetrance
Steroid Receptors
Glutamine
Proportional Hazards Models
polyglutamine
DNA

All Science Journal Classification (ASJC) codes

  • Cancer Research
  • Oncology

Cite this

Hughes, D. J., Ginolhac, S. M., Coupier, I., Barjhoux, L., Gaborieau, V., Bressac-De-Paillerets, B., ... Sinilnikova, O. M. (2005). Breast cancer risk in BRCA1 and BRCA2 mutation carriers and polyglutamine repeat length in the AIB1 gene. International Journal of Cancer, 117(2), 230-233. https://doi.org/10.1002/ijc.21176

Breast cancer risk in BRCA1 and BRCA2 mutation carriers and polyglutamine repeat length in the AIB1 gene. / Hughes, David J.; Ginolhac, Sophie M.; Coupier, Isabelle; Barjhoux, Laure; Gaborieau, Valérie; Bressac-De-Paillerets, Brigitte; Chompret, Agnès; Bignon, Yves Jean; Uhrhammer, Nancy; Lasset, Christine; Giraud, Sophie; Sobol, Hagay; Hardouin, Agnès; Berthet, Pascaline; Peyrat, Jean Philippe; Fournier, Joelle; Nogues, Catherine; Lidereau, Rosette; Muller, Danièle; Fricker, Jean Pierre; Longy, Michel; Toulas, Christine; Guimbaud, Rosine; Yannoukakos, Drakoulis; Mazoyer, Sylvie; Lynch, Henry T.; Lenoir, Gilbert M.; Goldgar, David E.; Stoppa-Lyonnet, Dominique; Sinilnikova, Olga M.

In: International Journal of Cancer, Vol. 117, No. 2, 01.11.2005, p. 230-233.

Research output: Contribution to journalArticle

Hughes, DJ, Ginolhac, SM, Coupier, I, Barjhoux, L, Gaborieau, V, Bressac-De-Paillerets, B, Chompret, A, Bignon, YJ, Uhrhammer, N, Lasset, C, Giraud, S, Sobol, H, Hardouin, A, Berthet, P, Peyrat, JP, Fournier, J, Nogues, C, Lidereau, R, Muller, D, Fricker, JP, Longy, M, Toulas, C, Guimbaud, R, Yannoukakos, D, Mazoyer, S, Lynch, HT, Lenoir, GM, Goldgar, DE, Stoppa-Lyonnet, D & Sinilnikova, OM 2005, 'Breast cancer risk in BRCA1 and BRCA2 mutation carriers and polyglutamine repeat length in the AIB1 gene', International Journal of Cancer, vol. 117, no. 2, pp. 230-233. https://doi.org/10.1002/ijc.21176
Hughes DJ, Ginolhac SM, Coupier I, Barjhoux L, Gaborieau V, Bressac-De-Paillerets B et al. Breast cancer risk in BRCA1 and BRCA2 mutation carriers and polyglutamine repeat length in the AIB1 gene. International Journal of Cancer. 2005 Nov 1;117(2):230-233. https://doi.org/10.1002/ijc.21176
Hughes, David J. ; Ginolhac, Sophie M. ; Coupier, Isabelle ; Barjhoux, Laure ; Gaborieau, Valérie ; Bressac-De-Paillerets, Brigitte ; Chompret, Agnès ; Bignon, Yves Jean ; Uhrhammer, Nancy ; Lasset, Christine ; Giraud, Sophie ; Sobol, Hagay ; Hardouin, Agnès ; Berthet, Pascaline ; Peyrat, Jean Philippe ; Fournier, Joelle ; Nogues, Catherine ; Lidereau, Rosette ; Muller, Danièle ; Fricker, Jean Pierre ; Longy, Michel ; Toulas, Christine ; Guimbaud, Rosine ; Yannoukakos, Drakoulis ; Mazoyer, Sylvie ; Lynch, Henry T. ; Lenoir, Gilbert M. ; Goldgar, David E. ; Stoppa-Lyonnet, Dominique ; Sinilnikova, Olga M. / Breast cancer risk in BRCA1 and BRCA2 mutation carriers and polyglutamine repeat length in the AIB1 gene. In: International Journal of Cancer. 2005 ; Vol. 117, No. 2. pp. 230-233.
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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.",
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AU - Barjhoux, Laure

AU - Gaborieau, Valérie

AU - Bressac-De-Paillerets, Brigitte

AU - Chompret, Agnès

AU - Bignon, Yves Jean

AU - Uhrhammer, Nancy

AU - Lasset, Christine

AU - Giraud, Sophie

AU - Sobol, Hagay

AU - Hardouin, Agnès

AU - Berthet, Pascaline

AU - Peyrat, Jean Philippe

AU - Fournier, Joelle

AU - Nogues, Catherine

AU - Lidereau, Rosette

AU - Muller, Danièle

AU - Fricker, Jean Pierre

AU - Longy, Michel

AU - Toulas, Christine

AU - Guimbaud, Rosine

AU - Yannoukakos, Drakoulis

AU - Mazoyer, Sylvie

AU - Lynch, Henry T.

AU - Lenoir, Gilbert M.

AU - Goldgar, David E.

AU - Stoppa-Lyonnet, Dominique

AU - Sinilnikova, Olga M.

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