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Variation in BRCA1 cancer risks by mutation position

Thompson, Deborah; Easton, Douglas; Borg, Åke LU ; Loman, Niklas LU ; Johannsson, O; Olsson, Håkan LU and , (2002) In Cancer Epidemiology Biomarkers & Prevention 11(4). p.329-336
Abstract
Previous studies have reported variation in BRCA1 breast and ovarian cancer risks with mutation position, suggesting that mutations toward the 3' end of the gene are associated with lower ovarian cancer risks. We evaluated the evidence for genotype-phenotype correlations in 356 families with protein-truncating BRCA1 mutations. In contrast to previous reports, the ovarian:breast cancer ratio associated with mutations in a central region of the gene (nucleotides 2401–4190) was significantly higher than for other mutations [odds ratio, 1.70 (P = 0.017) compared with nucleotides 1–2400; odds ratio, 1.89 (P = 0.02) compared with nucleotides 4191–end]. The risks of breast and ovarian cancer conferred by mutations in different regions of the gene... (More)
Previous studies have reported variation in BRCA1 breast and ovarian cancer risks with mutation position, suggesting that mutations toward the 3' end of the gene are associated with lower ovarian cancer risks. We evaluated the evidence for genotype-phenotype correlations in 356 families with protein-truncating BRCA1 mutations. In contrast to previous reports, the ovarian:breast cancer ratio associated with mutations in a central region of the gene (nucleotides 2401–4190) was significantly higher than for other mutations [odds ratio, 1.70 (P = 0.017) compared with nucleotides 1–2400; odds ratio, 1.89 (P = 0.02) compared with nucleotides 4191–end]. The risks of breast and ovarian cancer conferred by mutations in different regions of the gene were estimated separately by conditional maximum likelihood. According to the best fitting model, the breast cancer risk associated with mutations in the central region was found to be significantly lower than for other mutations (relative risk, 0.71; 95% confidence interval, 0.58–0.86; P = 0.0002), whereas the ovarian cancer risk associated with mutations 3' to nucleotide 4191 was significantly reduced relative to the rest of the gene (relative risk, 0.81; 95% confidence interval, 0.66–1.00; P = 0.044). The cancer risks associated with missense mutations in the RING domain in exon 5 appear to be similar to those associated with protein-truncating mutations toward the 3' end of BRCA1, based on nine additional families. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cancer Epidemiology Biomarkers & Prevention
volume
11
issue
4
pages
329 - 336
publisher
American Association for Cancer Research
external identifiers
  • wos:000174908000001
  • scopus:0036123926
ISSN
1538-7755
language
English
LU publication?
yes
id
a9258659-ef2d-45d5-8a04-0d3549499900 (old id 1123906)
alternative location
http://cebp.aacrjournals.org/cgi/content/full/11/4/329
date added to LUP
2008-05-20 15:40:01
date last changed
2017-12-10 04:33:37
@article{a9258659-ef2d-45d5-8a04-0d3549499900,
  abstract     = {Previous studies have reported variation in BRCA1 breast and ovarian cancer risks with mutation position, suggesting that mutations toward the 3' end of the gene are associated with lower ovarian cancer risks. We evaluated the evidence for genotype-phenotype correlations in 356 families with protein-truncating BRCA1 mutations. In contrast to previous reports, the ovarian:breast cancer ratio associated with mutations in a central region of the gene (nucleotides 2401–4190) was significantly higher than for other mutations [odds ratio, 1.70 (P = 0.017) compared with nucleotides 1–2400; odds ratio, 1.89 (P = 0.02) compared with nucleotides 4191–end]. The risks of breast and ovarian cancer conferred by mutations in different regions of the gene were estimated separately by conditional maximum likelihood. According to the best fitting model, the breast cancer risk associated with mutations in the central region was found to be significantly lower than for other mutations (relative risk, 0.71; 95% confidence interval, 0.58–0.86; P = 0.0002), whereas the ovarian cancer risk associated with mutations 3' to nucleotide 4191 was significantly reduced relative to the rest of the gene (relative risk, 0.81; 95% confidence interval, 0.66–1.00; P = 0.044). The cancer risks associated with missense mutations in the RING domain in exon 5 appear to be similar to those associated with protein-truncating mutations toward the 3' end of BRCA1, based on nine additional families.},
  author       = {Thompson, Deborah and Easton, Douglas and Borg, Åke and Loman, Niklas and Johannsson, O and Olsson, Håkan and , },
  issn         = {1538-7755},
  language     = {eng},
  number       = {4},
  pages        = {329--336},
  publisher    = {American Association for Cancer Research},
  series       = {Cancer Epidemiology Biomarkers & Prevention},
  title        = {Variation in BRCA1 cancer risks by mutation position},
  volume       = {11},
  year         = {2002},
}