Modification of ovarian cancer risk by BRCA1/2-interacting genes in a multicenter cohort of BRCA1/2 mutation carriers

Timothy R. Rebbeck, Nandita Mitra, Susan M. Domchek, Fei Wan, Shannon Chuai, Tara M. Friebel, Saarene Panossian, Amanda Spurdle, Georgia Chenevix-Trench, Christian F. Singer, Georg Pfeiler, Susan L. Neuhausen, Henry T. Lynch, Judy E. Garber, Jeffrey N. Weitzel, Claudine Isaacs, Fergus Couch, Steven A. Narod, Wendy S. Rubinstein, Gail E. Tomlinson & 7 others Patricia A. Ganz, Olufunmilayo I. Olopade, Nadine Tung, Joanne L. Blum, Roger Greenberg, Katherine L. Nathanson, Mary B. Daly

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Abstract

Inherited BRCA1/2 mutations confer elevated ovarian cancer risk. Knowledge of factors that can improve ovarian cancer risk assessment in BRCA1/2 mutation carriers is important because no effective early detection for ovarian cancers exists. A cohort of 1,575 BRCA1 and 856 BRCA2 mutation carriers was used to evaluate haplotypes at ATM, BARD1, BRIP1, CTIP, MRE11, NBS1, RAD50, RAD51, and TOPBP1 in ovarian cancer risk. In BRCA1 carriers, no associations were observed with ATM, BARD1, CTIP, RAD50, RAD51, or TOPBP1. At BRIP1, an association was observed for one haplotype with a multiple testing corrected P (P corr) = 0.012, although no individual haplotype was significant. At MRE11, statistically significant associations were observed for one haplotype (Pcorr = 0.007). At NBS1, we observed a Pcorr = 0.024 for haplotypes. In BRCA2 carriers, no associations were observed with CTIP, NBS1, RAD50, or TOPBP1. Rare haplotypes at ATM (Pcorr = 0.044) and BARD1 (Pcorr = 0.012) were associated with ovarian cancer risk. At BRIP1, two common haplotypes were significantly associated with ovarian cancer risk (Pcorr = 0.011). At MRE11, we observed a significant haplotype association (Pcorr = 0.012), and at RAD51, one common haplotype was significantly associated with ovarian cancer risk (Pcorr = 0.026). Variants in genes that interact biologically with BRCA1 and/or BRCA2 may be associated with modified ovarian cancer risk in women who carry BRCA1/2 mutations.

Original languageEnglish
Pages (from-to)5801-5810
Number of pages10
JournalCancer Research
Volume69
Issue number14
DOIs
StatePublished - Jul 15 2009

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Ovarian Neoplasms
Haplotypes
Mutation
Genes
Early Detection of Cancer

All Science Journal Classification (ASJC) codes

  • Cancer Research
  • Oncology

Cite this

Rebbeck, T. R., Mitra, N., Domchek, S. M., Wan, F., Chuai, S., Friebel, T. M., ... Daly, M. B. (2009). Modification of ovarian cancer risk by BRCA1/2-interacting genes in a multicenter cohort of BRCA1/2 mutation carriers. Cancer Research, 69(14), 5801-5810. https://doi.org/10.1158/0008-5472.CAN-09-0625

Modification of ovarian cancer risk by BRCA1/2-interacting genes in a multicenter cohort of BRCA1/2 mutation carriers. / Rebbeck, Timothy R.; Mitra, Nandita; Domchek, Susan M.; Wan, Fei; Chuai, Shannon; Friebel, Tara M.; Panossian, Saarene; Spurdle, Amanda; Chenevix-Trench, Georgia; Singer, Christian F.; Pfeiler, Georg; Neuhausen, Susan L.; Lynch, Henry T.; Garber, Judy E.; Weitzel, Jeffrey N.; Isaacs, Claudine; Couch, Fergus; Narod, Steven A.; Rubinstein, Wendy S.; Tomlinson, Gail E.; Ganz, Patricia A.; Olopade, Olufunmilayo I.; Tung, Nadine; Blum, Joanne L.; Greenberg, Roger; Nathanson, Katherine L.; Daly, Mary B.

In: Cancer Research, Vol. 69, No. 14, 15.07.2009, p. 5801-5810.

Research output: Contribution to journalArticle

Rebbeck, TR, Mitra, N, Domchek, SM, Wan, F, Chuai, S, Friebel, TM, Panossian, S, Spurdle, A, Chenevix-Trench, G, Singer, CF, Pfeiler, G, Neuhausen, SL, Lynch, HT, Garber, JE, Weitzel, JN, Isaacs, C, Couch, F, Narod, SA, Rubinstein, WS, Tomlinson, GE, Ganz, PA, Olopade, OI, Tung, N, Blum, JL, Greenberg, R, Nathanson, KL & Daly, MB 2009, 'Modification of ovarian cancer risk by BRCA1/2-interacting genes in a multicenter cohort of BRCA1/2 mutation carriers', Cancer Research, vol. 69, no. 14, pp. 5801-5810. https://doi.org/10.1158/0008-5472.CAN-09-0625
Rebbeck, Timothy R. ; Mitra, Nandita ; Domchek, Susan M. ; Wan, Fei ; Chuai, Shannon ; Friebel, Tara M. ; Panossian, Saarene ; Spurdle, Amanda ; Chenevix-Trench, Georgia ; Singer, Christian F. ; Pfeiler, Georg ; Neuhausen, Susan L. ; Lynch, Henry T. ; Garber, Judy E. ; Weitzel, Jeffrey N. ; Isaacs, Claudine ; Couch, Fergus ; Narod, Steven A. ; Rubinstein, Wendy S. ; Tomlinson, Gail E. ; Ganz, Patricia A. ; Olopade, Olufunmilayo I. ; Tung, Nadine ; Blum, Joanne L. ; Greenberg, Roger ; Nathanson, Katherine L. ; Daly, Mary B. / Modification of ovarian cancer risk by BRCA1/2-interacting genes in a multicenter cohort of BRCA1/2 mutation carriers. In: Cancer Research. 2009 ; Vol. 69, No. 14. pp. 5801-5810.
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abstract = "Inherited BRCA1/2 mutations confer elevated ovarian cancer risk. Knowledge of factors that can improve ovarian cancer risk assessment in BRCA1/2 mutation carriers is important because no effective early detection for ovarian cancers exists. A cohort of 1,575 BRCA1 and 856 BRCA2 mutation carriers was used to evaluate haplotypes at ATM, BARD1, BRIP1, CTIP, MRE11, NBS1, RAD50, RAD51, and TOPBP1 in ovarian cancer risk. In BRCA1 carriers, no associations were observed with ATM, BARD1, CTIP, RAD50, RAD51, or TOPBP1. At BRIP1, an association was observed for one haplotype with a multiple testing corrected P (P corr) = 0.012, although no individual haplotype was significant. At MRE11, statistically significant associations were observed for one haplotype (Pcorr = 0.007). At NBS1, we observed a Pcorr = 0.024 for haplotypes. In BRCA2 carriers, no associations were observed with CTIP, NBS1, RAD50, or TOPBP1. Rare haplotypes at ATM (Pcorr = 0.044) and BARD1 (Pcorr = 0.012) were associated with ovarian cancer risk. At BRIP1, two common haplotypes were significantly associated with ovarian cancer risk (Pcorr = 0.011). At MRE11, we observed a significant haplotype association (Pcorr = 0.012), and at RAD51, one common haplotype was significantly associated with ovarian cancer risk (Pcorr = 0.026). Variants in genes that interact biologically with BRCA1 and/or BRCA2 may be associated with modified ovarian cancer risk in women who carry BRCA1/2 mutations.",
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AU - Rebbeck, Timothy R.

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AU - Domchek, Susan M.

AU - Wan, Fei

AU - Chuai, Shannon

AU - Friebel, Tara M.

AU - Panossian, Saarene

AU - Spurdle, Amanda

AU - Chenevix-Trench, Georgia

AU - Singer, Christian F.

AU - Pfeiler, Georg

AU - Neuhausen, Susan L.

AU - Lynch, Henry T.

AU - Garber, Judy E.

AU - Weitzel, Jeffrey N.

AU - Isaacs, Claudine

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AU - Narod, Steven A.

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AU - Olopade, Olufunmilayo I.

AU - Tung, Nadine

AU - Blum, Joanne L.

AU - Greenberg, Roger

AU - Nathanson, Katherine L.

AU - Daly, Mary B.

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