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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, PDP; Narod, S; Risch, HA; Eyfjord, JE; Hopper, JL; Loman, Niklas LU ; Olsson, H; Johannsson, O and Borg, Åke LU , et al. (2003) In American Journal of Human Genetics 72(5). p.1117-1130
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... (More)
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 <35 years of age. We found some evidence for a reduction in risk in women from earlier birth cohorts and for variation in risk by mutation position for both genes. The pattern of cancer risks was similar to those found in multiple-case families, but their absolute magnitudes were lower, particularly for BRCA2. The variation in risk by age at diagnosis of index case is consistent with the effects of other genes modifying cancer risk in carriers. (Less)
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American Journal of Human Genetics
volume
72
issue
5
pages
1117 - 1130
publisher
Cell Press
external identifiers
  • pmid:12677558
  • wos:000182474400005
  • scopus:0038744296
ISSN
0002-9297
DOI
10.1086/375033
language
English
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yes
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3936a3e3-1fa0-4196-934b-12960b753fb4 (old id 312881)
date added to LUP
2007-08-02 11:08:51
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2018-10-14 03:37:04
@article{3936a3e3-1fa0-4196-934b-12960b753fb4,
  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 &lt;35 years of age. We found some evidence for a reduction in risk in women from earlier birth cohorts and for variation in risk by mutation position for both genes. The pattern of cancer risks was similar to those found in multiple-case families, but their absolute magnitudes were lower, particularly for BRCA2. The variation in risk by age at diagnosis of index case is consistent with the effects of other genes modifying cancer risk in carriers.},
  author       = {Antoniou, A and Pharoah, PDP and Narod, S and Risch, HA and Eyfjord, JE and Hopper, JL and Loman, Niklas and Olsson, H and Johannsson, O and Borg, Åke and Pasini, B and Radice, P and Manoukian, S and Eccles, DM and Tang, N and Olah, E and Anton-Culver, H and Warner, E and Lubinski, J and Gronwald, J and Gorski, B and Tulinius, H and Thorlacius, S and Eerola, H and Nevanlinna, H and Syrjakoski, K and Kallioniemi, OP and Thompson, D and Evans, C and Peto, J and Lalloo, F and Evans, DG and Easton, DF},
  issn         = {0002-9297},
  language     = {eng},
  number       = {5},
  pages        = {1117--1130},
  publisher    = {Cell Press},
  series       = {American Journal of Human Genetics},
  title        = {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},
  url          = {http://dx.doi.org/10.1086/375033},
  volume       = {72},
  year         = {2003},
}