+ Site Statistics
References:
54,258,434
Abstracts:
29,560,870
PMIDs:
28,072,757
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

Breast and ovarian cancer risks in a large series of clinically ascertained families with a high proportion of BRCA1 and BRCA2 Dutch founder mutations



Breast and ovarian cancer risks in a large series of clinically ascertained families with a high proportion of BRCA1 and BRCA2 Dutch founder mutations



Journal of Medical Genetics 51(2): 98-107



BRCA1 or BRCA2 mutations confer increased risks of breast and ovarian cancer, but risks have been found to vary across studies and populations. We ascertained pedigree data of 582 BRCA1 and 176 BRCA2 families and studied the variation in breast and ovarian cancer risks using a modified segregation analysis model. The average cumulative breast cancer risk by age 70 years was estimated to be 45% (95% CI 36 to 52%) for BRCA1 and 27% (95% CI 14 to 38%) for BRCA2 mutation carriers. The corresponding cumulative risks for ovarian cancer were 31% (95% CI 17 to 43%) for BRCA1 and 6% (95% CI 2 to 11%) for BRCA2 mutation carriers. In BRCA1 families, breast cancer relative risk (RR) increased with more recent birth cohort (p heterogeneity = 0.0006) and stronger family histories of breast cancer (p heterogeneity < 0.001). For BRCA1, our data suggest a significant association between the location of the mutation and the ratio of breast to ovarian cancer (p<0.001). By contrast, in BRCA2 families, no evidence was found for risk heterogeneity by birth cohort, family history or mutation location. BRCA1 mutation carriers conferred lower overall breast and ovarian cancer risks than reported so far, while the estimates of BRCA2 mutations were among the lowest. The low estimates for BRCA1 might be due to older birth cohorts, a moderate family history, or founder mutations located within specific regions of the gene. These results are important for a more accurate counselling of BRCA1/2 mutation carriers.

(PDF emailed within 0-6 h: $19.90)

Accession: 051861635

Download citation: RISBibTeXText

PMID: 24285858

DOI: 10.1136/jmedgenet-2013-101974


Related references

A high proportion of novel mutations in BRCA1 with strong founder effects among Dutch and Belgian hereditary breast and ovarian cancer families. American Journal of Human Genetics 60(5): 1041-1049, 1997

High frequency of pathogenic non-founder germline mutations in BRCA1 and BRCA2 in families with breast and ovarian cancer in a founder population. Hereditary Cancer in Clinical Practice 16: 12-12, 2018

Incidence of non-founder BRCA1 and BRCA2 mutations in high risk Ashkenazi breast and ovarian cancer families. Journal of Medical Genetics 39(8): 611-614, 2002

High proportion of BRCA1/2 founder mutations in Hispanic breast/ovarian cancer families from Colombia. Breast Cancer Research and Treatment 103(2): 225-232, 2006

Fifty percent of Jewish high-risk breast and ovarian cancer families are not explained by the three known BRCA1 or BRCA2 founder mutations while a 07 percent combined BRCA1 founder mutation frequency is reported in a Jewish cohort. American Journal of Human Genetics 59(4 SUPPL ): A28, 1996

Large regional differences in the frequency of distinct BRCA1/BRCA2 mutations in 517 Dutch breast and/or ovarian cancer families. European Journal of Cancer 37(16): 2082-2090, November, 2001

Analysis of BRCA1 and BRCA2 genes in Spanish breast/ovarian cancer patients: a high proportion of mutations unique to Spain and evidence of founder effects. Human Mutation 22(4): 301-312, 2003

BRCA1 5272-1G>A and BRCA2 5374delTATG are founder mutations of high relevance for genetic counselling in breast/ovarian cancer families of Spanish origin. Clinical Genetics 77(1): 60-69, 2010

Founder BRCA1 and BRCA2 mutations in French Canadian breast and ovarian cancer families. American Journal of Human Genetics 63(5): 1341-1351, 1998

Founder BRCA1 mutations and two novel germline BRCA2 mutations in breast and/or ovarian cancer families from North-Eastern Poland. Human Mutation 15(5): 480-481, 2000

Ashkenazi founder BRCA1/BRCA2 mutations in Slovak hereditary breast and/or ovarian cancer families. Neoplasma 53(2): 97-102, 2006

Prevalence of BRCA1 and BRCA2 founder mutations in Brazilian hereditary breast and ovarian cancer families. Journal of Clinical Oncology 26(15_suppl): 22108-22108, 2016

Founder BRCA1 and BRCA2 mutations in Ashkenazi Jews in Israel: frequency and differential penetrance in ovarian cancer and in breast-ovarian cancer families. American Journal of Human Genetics 60(5): 1059-1067, 1997

Childhood cancer in families with and without BRCA1 or BRCA2 mutations ascertained at a high-risk breast cancer clinic. Cancer Biology & Therapy 5(9): 1098-1102, 2006

BRCA1 and BRCA2 mutations in breast and ovarian cancer syndrome: reflection on the Creighton University historical series of high risk families. Familial Cancer 5(1): 15-20, 2006