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Cancer risks in BRCA2 mutation carriers

, and Olsson, Håkan LU (1999) In Journal of the National Cancer Institute 91(15). p.6-1310
Abstract

BACKGROUND: Carriers of germline mutations in the BRCA2 gene are known to be at high risk of breast and ovarian cancers, but the risks of other cancers in mutation carriers are uncertain. We investigated these risks in 173 breast-ovarian cancer families with BRCA2 mutations identified at 20 centers in Europe and North America.

METHODS: Other cancer occurrence was determined in a final cohort of 3728 individuals, among whom 681 persons had breast or ovarian cancer and 3047 persons either were known mutation carriers, were first-degree relatives of known mutation carriers, or were first-degree relatives of breast or ovarian cancer patients. Incidence rates were compared with population-specific incidence rates, and relative risks... (More)

BACKGROUND: Carriers of germline mutations in the BRCA2 gene are known to be at high risk of breast and ovarian cancers, but the risks of other cancers in mutation carriers are uncertain. We investigated these risks in 173 breast-ovarian cancer families with BRCA2 mutations identified at 20 centers in Europe and North America.

METHODS: Other cancer occurrence was determined in a final cohort of 3728 individuals, among whom 681 persons had breast or ovarian cancer and 3047 persons either were known mutation carriers, were first-degree relatives of known mutation carriers, or were first-degree relatives of breast or ovarian cancer patients. Incidence rates were compared with population-specific incidence rates, and relative risks (RRs) to carriers, together with 95% confidence intervals (CIs), were estimated by use of a maximum likelihood approach. Three hundred thirty-three other cancers occurred in this cohort.

RESULTS: Statistically significant increases in risks were observed for prostate cancer (estimated RR = 4.65; 95% CI = 3.48-6.22), pancreatic cancer (RR = 3.51; 95% CI = 1. 87-6.58), gallbladder and bile duct cancer (RR = 4.97; 95% CI = 1. 50-16.52), stomach cancer (RR = 2.59; 95%CI = 1.46-4.61), and malignant melanoma (RR = 2.58; 95% CI = 1.28-5.17). The RR for prostate cancer for men below the age of 65 years was 7.33 (95% CI = 4.66-11.52). Among women who had already developed breast cancer, the cumulative risks of a second, contralateral breast cancer and of ovarian cancer by the age of 70 years were estimated to be 52.3% (95% CI = 41.7%-61.0%) and 15.9% (95% CI = 8.8%-22.5%), respectively.

CONCLUSIONS: In addition to the large risks of breast and ovarian cancers, BRCA2 mutations may be associated with increased risks of several other cancers.

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keywords
Adolescent, Adult, Aged, Aged, 80 and over, Biliary Tract Neoplasms, Breast Neoplasms, Child, Child, Preschool, Europe, Female, Genes, Tumor Suppressor, Heterozygote, Humans, Infant, Male, Melanoma, Middle Aged, Mutation, Neoplasms, Neoplasms, Second Primary, North America, Ovarian Neoplasms, Pancreatic Neoplasms, Prostatic Neoplasms, Risk, Skin Neoplasms, Stomach Neoplasms
in
Journal of the National Cancer Institute
volume
91
issue
15
pages
7 pages
publisher
Oxford University Press
external identifiers
  • scopus:0033523268
ISSN
0027-8874
DOI
10.1093/jnci/91.15.1310
language
English
LU publication?
yes
id
36bb361c-d123-4976-854f-5c682364b235
date added to LUP
2016-09-18 12:32:59
date last changed
2017-08-13 04:58:03
@article{36bb361c-d123-4976-854f-5c682364b235,
  abstract     = {<p>BACKGROUND: Carriers of germline mutations in the BRCA2 gene are known to be at high risk of breast and ovarian cancers, but the risks of other cancers in mutation carriers are uncertain. We investigated these risks in 173 breast-ovarian cancer families with BRCA2 mutations identified at 20 centers in Europe and North America.</p><p>METHODS: Other cancer occurrence was determined in a final cohort of 3728 individuals, among whom 681 persons had breast or ovarian cancer and 3047 persons either were known mutation carriers, were first-degree relatives of known mutation carriers, or were first-degree relatives of breast or ovarian cancer patients. Incidence rates were compared with population-specific incidence rates, and relative risks (RRs) to carriers, together with 95% confidence intervals (CIs), were estimated by use of a maximum likelihood approach. Three hundred thirty-three other cancers occurred in this cohort.</p><p>RESULTS: Statistically significant increases in risks were observed for prostate cancer (estimated RR = 4.65; 95% CI = 3.48-6.22), pancreatic cancer (RR = 3.51; 95% CI = 1. 87-6.58), gallbladder and bile duct cancer (RR = 4.97; 95% CI = 1. 50-16.52), stomach cancer (RR = 2.59; 95%CI = 1.46-4.61), and malignant melanoma (RR = 2.58; 95% CI = 1.28-5.17). The RR for prostate cancer for men below the age of 65 years was 7.33 (95% CI = 4.66-11.52). Among women who had already developed breast cancer, the cumulative risks of a second, contralateral breast cancer and of ovarian cancer by the age of 70 years were estimated to be 52.3% (95% CI = 41.7%-61.0%) and 15.9% (95% CI = 8.8%-22.5%), respectively.</p><p>CONCLUSIONS: In addition to the large risks of breast and ovarian cancers, BRCA2 mutations may be associated with increased risks of several other cancers.</p>},
  author       = {,  and Olsson, Håkan},
  issn         = {0027-8874},
  keyword      = {Adolescent,Adult,Aged,Aged, 80 and over,Biliary Tract Neoplasms,Breast Neoplasms,Child,Child, Preschool,Europe,Female,Genes, Tumor Suppressor,Heterozygote,Humans,Infant,Male,Melanoma,Middle Aged,Mutation,Neoplasms,Neoplasms, Second Primary,North America,Ovarian Neoplasms,Pancreatic Neoplasms,Prostatic Neoplasms,Risk,Skin Neoplasms,Stomach Neoplasms},
  language     = {eng},
  month        = {08},
  number       = {15},
  pages        = {6--1310},
  publisher    = {Oxford University Press},
  series       = {Journal of the National Cancer Institute},
  title        = {Cancer risks in BRCA2 mutation carriers},
  url          = {http://dx.doi.org/10.1093/jnci/91.15.1310},
  volume       = {91},
  year         = {1999},
}