Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history

A combined analysis of 22 studies

A. Antoniou, P. D P Pharoah, S. Narod, H. A. Risch, J. E. Eyfjord, J. L. Hopper, N. Loman, H. Olsson, O. Johannsson, Å Borg, B. Pasini, P. Radice, S. Manoukian, D. M. Eccles, N. Tang, E. Olah, H. Anton-Culver, E. Warner, J. Lubinski, J. Gronwald & 13 others B. Gorski, H. Tulinius, S. Thorlacius, H. Eerola, H. Nevanlinna, K. Syrjäkoski, O. P. Kallioniemi, D. Thompson, C. Evans, J. Peto, F. Lalloo, D. G. Evans, D. F. Easton

Research output: Contribution to journal › Article

2271 Citations (Scopus)

Abstract

Germline mutations in BRCA1 and BRCA2 confer high risks of breast and ovarian cancer, but the average magnitude of these risks is uncertain and may depend on the context. Estimates based on multiple-case families may be enriched for mutations of higher risk and/or other familial risk factors, whereas risk estimates from studies based on cases unselected for family history have been imprecise. We pooled pedigree data from 22 studies involving 8,139 index case patients unselected for family history with female (86%) or male (2%) breast cancer or epithelial ovarian cancer (12%), 500 of whom had been found to carry a germline mutation in BRCA1 or BRCA2. Breast and ovarian cancer incidence rates for mutation carriers were estimated using a modified segregation analysis, based on the occurrence of these cancers in the relatives of mutation-carrying index case patients. The average cumulative risks in BRCA1-mutation carriers by age 70 years were 65% (95% confidence interval 44%-78%) for breast cancer and 39% (18%-54%) for ovarian cancer. The corresponding estimates for BRCA2 were 45% (31%-56%) and 11% (2.4%-19%). Relative risks of breast cancer declined significantly with age for BRCA1-mutation carriers (P trend .0012) but not for BRCA2-mutation carriers. Risks in carriers were higher when based on index breast cancer cases diagnosed at

Original languageEnglish
Pages (from-to)1117-1130
Number of pages14
JournalAmerican Journal of Human Genetics
Volume72
Issue number5
DOIs
Publication statusPublished - May 1 2003

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Ovarian Neoplasms
Breast Neoplasms
Mutation
Germ-Line Mutation
Male Breast Neoplasms
Mutation Rate
Pedigree
Confidence Intervals
Incidence
Neoplasms

ASJC Scopus subject areas

  • Genetics

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Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history : A combined analysis of 22 studies. / Antoniou, A.; Pharoah, P. D P; Narod, S.; Risch, H. A.; Eyfjord, J. E.; Hopper, J. L.; Loman, N.; Olsson, H.; Johannsson, O.; Borg, Å; Pasini, B.; Radice, P.; Manoukian, S.; Eccles, D. M.; Tang, N.; Olah, E.; Anton-Culver, H.; Warner, E.; Lubinski, J.; Gronwald, J.; Gorski, B.; Tulinius, H.; Thorlacius, S.; Eerola, H.; Nevanlinna, H.; Syrjäkoski, K.; Kallioniemi, O. P.; Thompson, D.; Evans, C.; Peto, J.; Lalloo, F.; Evans, D. G.; Easton, D. F.

In: American Journal of Human Genetics, Vol. 72, No. 5, 01.05.2003, p. 1117-1130.

Research output: Contribution to journal › Article

Antoniou, A, Pharoah, PDP, Narod, S, Risch, HA, Eyfjord, JE, Hopper, JL, Loman, N, Olsson, H, Johannsson, O, Borg, Å, Pasini, B, Radice, P, Manoukian, S, Eccles, DM, Tang, N, Olah, E, Anton-Culver, H, Warner, E, Lubinski, J, Gronwald, J, Gorski, B, Tulinius, H, Thorlacius, S, Eerola, H, Nevanlinna, H, Syrjäkoski, K, Kallioniemi, OP, Thompson, D, Evans, C, Peto, J, Lalloo, F, Evans, DG & Easton, DF 2003, 'Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history: A combined analysis of 22 studies', American Journal of Human Genetics, vol. 72, no. 5, pp. 1117-1130. https://doi.org/10.1086/375033
Antoniou A, Pharoah PDP, Narod S, Risch HA, Eyfjord JE, Hopper JL et al. Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history: A combined analysis of 22 studies. American Journal of Human Genetics. 2003 May 1;72(5):1117-1130. https://doi.org/10.1086/375033
Antoniou, A. ; Pharoah, P. D P ; Narod, S. ; Risch, H. A. ; Eyfjord, J. E. ; Hopper, J. L. ; Loman, N. ; Olsson, H. ; Johannsson, O. ; Borg, Å ; Pasini, B. ; Radice, P. ; Manoukian, S. ; Eccles, D. M. ; Tang, N. ; Olah, E. ; Anton-Culver, H. ; Warner, E. ; Lubinski, J. ; Gronwald, J. ; Gorski, B. ; Tulinius, H. ; Thorlacius, S. ; Eerola, H. ; Nevanlinna, H. ; Syrjäkoski, K. ; Kallioniemi, O. P. ; Thompson, D. ; Evans, C. ; Peto, J. ; Lalloo, F. ; Evans, D. G. ; Easton, D. F. / Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history : A combined analysis of 22 studies. In: American Journal of Human Genetics. 2003 ; Vol. 72, No. 5. pp. 1117-1130.
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abstract = "Germline mutations in BRCA1 and BRCA2 confer high risks of breast and ovarian cancer, but the average magnitude of these risks is uncertain and may depend on the context. Estimates based on multiple-case families may be enriched for mutations of higher risk and/or other familial risk factors, whereas risk estimates from studies based on cases unselected for family history have been imprecise. We pooled pedigree data from 22 studies involving 8,139 index case patients unselected for family history with female (86{\%}) or male (2{\%}) breast cancer or epithelial ovarian cancer (12{\%}), 500 of whom had been found to carry a germline mutation in BRCA1 or BRCA2. Breast and ovarian cancer incidence rates for mutation carriers were estimated using a modified segregation analysis, based on the occurrence of these cancers in the relatives of mutation-carrying index case patients. The average cumulative risks in BRCA1-mutation carriers by age 70 years were 65{\%} (95{\%} confidence interval 44{\%}-78{\%}) for breast cancer and 39{\%} (18{\%}-54{\%}) for ovarian cancer. The corresponding estimates for BRCA2 were 45{\%} (31{\%}-56{\%}) and 11{\%} (2.4{\%}-19{\%}). Relative risks of breast cancer declined significantly with age for BRCA1-mutation carriers (P trend .0012) but not for BRCA2-mutation carriers. Risks in carriers were higher when based on index breast cancer cases diagnosed at",
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T1 - Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history

T2 - A combined analysis of 22 studies

AU - Antoniou, A.

AU - Pharoah, P. D P

AU - Narod, S.

AU - Risch, H. A.

AU - Eyfjord, J. E.

AU - Hopper, J. L.

AU - Loman, N.

AU - Olsson, H.

AU - Johannsson, O.

AU - Borg, Å

AU - Pasini, B.

AU - Radice, P.

AU - Manoukian, S.

AU - Eccles, D. M.

AU - Tang, N.

AU - Olah, E.

AU - Anton-Culver, H.

AU - Warner, E.

AU - Lubinski, J.

AU - Gronwald, J.

AU - Gorski, B.

AU - Tulinius, H.

AU - Thorlacius, S.

AU - Eerola, H.

AU - Nevanlinna, H.

AU - Syrjäkoski, K.

AU - Kallioniemi, O. P.

AU - Thompson, D.

AU - Evans, C.

AU - Peto, J.

AU - Lalloo, F.

AU - Evans, D. G.

AU - Easton, D. F.

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