Modification of BRCA1- and BRCA2-associated breast cancer risk by AIB1 genotype and reproductive history

T. R. Rebbeck, Y. Wang, P. W. Kantoff, K. Krithivas, S. L. Neuhausen, A. K. Godwin, M. B. Daly, S. A. Narod, J. S. Brunet, D. Vesprini, J. E. Garber, Henry T. Lynch, B. L. Weber, M. Brown

Research output: Contribution to journalArticle

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Abstract

Women who have inherited a germ-line mutation in the BRCA1 or BRCA2 (BRCA1/2) genes have a greatly increased risk of developing breast cancer compared with the general population. However, there is also substantial interindividual variability in the occurrence of breast cancer among BRCA1/2 mutation carriers. We hypothesize that genes involved in endocrine signaling may modify the BRCA1/2-associated age-specific breast cancer penetrance. We studied the effect of alleles at the AIB1 gene using a matched case-control sample of 448 women with germ-line BRCA1/2 mutations. We found that these women were at significantly higher breast cancer risk if they carried alleles with at least 28 or 29 polyglutamine repeats at AIB1, compared with women who carried alleles with fewer polyglutamine repeats [odds ratio (OR), 1.59; 95% confidence interval (CI), 1.03-2.47 and OR, 2.85; 95% CI, 1.64-4.96, respectively]. Late age at first live birth and nulliparity have been associated with increased breast cancer risk. We observed increases in BRCA1/2-associated breast cancer risk in women who were either nulliparous or had their first live birth after age 30 (OR, 3.06; 95% CI, 1.52-6.16). Women were at significantly increased risk if they were nulliparous or had a late age at first live birth and had AIB1 alleles no shorter than 28 or 29 or more AIB1 polyglutamine repeats (OR, 4.62; 95% CI, 2.02-10.56 and OR, 6.97; 95% CI, 1.71-28.43, respectively) than women with none of these risk factors. Our results support the hypothesis that pathways involving endocrine signaling, as measured through AIB1 genotype and reproductive history, may have a substantial effect on BRCAI/2-associated breast cancer risk.

Original languageEnglish
Pages (from-to)5420-5424
Number of pages5
JournalCancer Research
Volume61
Issue number14
StatePublished - Jul 15 2001

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Reproductive History
Genotype
Breast Neoplasms
Odds Ratio
Birth Order
Confidence Intervals
Live Birth
Alleles
BRCA1 Gene
Mutation
Penetrance
Germ-Line Mutation
Parity
Germ Cells
Genes
Population
polyglutamine

All Science Journal Classification (ASJC) codes

  • Cancer Research
  • Oncology

Cite this

Rebbeck, T. R., Wang, Y., Kantoff, P. W., Krithivas, K., Neuhausen, S. L., Godwin, A. K., ... Brown, M. (2001). Modification of BRCA1- and BRCA2-associated breast cancer risk by AIB1 genotype and reproductive history. Cancer Research, 61(14), 5420-5424.

Modification of BRCA1- and BRCA2-associated breast cancer risk by AIB1 genotype and reproductive history. / Rebbeck, T. R.; Wang, Y.; Kantoff, P. W.; Krithivas, K.; Neuhausen, S. L.; Godwin, A. K.; Daly, M. B.; Narod, S. A.; Brunet, J. S.; Vesprini, D.; Garber, J. E.; Lynch, Henry T.; Weber, B. L.; Brown, M.

In: Cancer Research, Vol. 61, No. 14, 15.07.2001, p. 5420-5424.

Research output: Contribution to journalArticle

Rebbeck, TR, Wang, Y, Kantoff, PW, Krithivas, K, Neuhausen, SL, Godwin, AK, Daly, MB, Narod, SA, Brunet, JS, Vesprini, D, Garber, JE, Lynch, HT, Weber, BL & Brown, M 2001, 'Modification of BRCA1- and BRCA2-associated breast cancer risk by AIB1 genotype and reproductive history', Cancer Research, vol. 61, no. 14, pp. 5420-5424.
Rebbeck TR, Wang Y, Kantoff PW, Krithivas K, Neuhausen SL, Godwin AK et al. Modification of BRCA1- and BRCA2-associated breast cancer risk by AIB1 genotype and reproductive history. Cancer Research. 2001 Jul 15;61(14):5420-5424.
Rebbeck, T. R. ; Wang, Y. ; Kantoff, P. W. ; Krithivas, K. ; Neuhausen, S. L. ; Godwin, A. K. ; Daly, M. B. ; Narod, S. A. ; Brunet, J. S. ; Vesprini, D. ; Garber, J. E. ; Lynch, Henry T. ; Weber, B. L. ; Brown, M. / Modification of BRCA1- and BRCA2-associated breast cancer risk by AIB1 genotype and reproductive history. In: Cancer Research. 2001 ; Vol. 61, No. 14. pp. 5420-5424.
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abstract = "Women who have inherited a germ-line mutation in the BRCA1 or BRCA2 (BRCA1/2) genes have a greatly increased risk of developing breast cancer compared with the general population. However, there is also substantial interindividual variability in the occurrence of breast cancer among BRCA1/2 mutation carriers. We hypothesize that genes involved in endocrine signaling may modify the BRCA1/2-associated age-specific breast cancer penetrance. We studied the effect of alleles at the AIB1 gene using a matched case-control sample of 448 women with germ-line BRCA1/2 mutations. We found that these women were at significantly higher breast cancer risk if they carried alleles with at least 28 or 29 polyglutamine repeats at AIB1, compared with women who carried alleles with fewer polyglutamine repeats [odds ratio (OR), 1.59; 95{\%} confidence interval (CI), 1.03-2.47 and OR, 2.85; 95{\%} CI, 1.64-4.96, respectively]. Late age at first live birth and nulliparity have been associated with increased breast cancer risk. We observed increases in BRCA1/2-associated breast cancer risk in women who were either nulliparous or had their first live birth after age 30 (OR, 3.06; 95{\%} CI, 1.52-6.16). Women were at significantly increased risk if they were nulliparous or had a late age at first live birth and had AIB1 alleles no shorter than 28 or 29 or more AIB1 polyglutamine repeats (OR, 4.62; 95{\%} CI, 2.02-10.56 and OR, 6.97; 95{\%} CI, 1.71-28.43, respectively) than women with none of these risk factors. Our results support the hypothesis that pathways involving endocrine signaling, as measured through AIB1 genotype and reproductive history, may have a substantial effect on BRCAI/2-associated breast cancer risk.",
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AU - Neuhausen, S. L.

AU - Godwin, A. K.

AU - Daly, M. B.

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