BRCA1/BRA2 founder mutations and cancer risks: impact in the western Danish population

Henriette Roed Nielsen; Mef Christina Nilbert; Janne Petersen; Steen Ladelund; Mads Thomassen; Inge Søkilde Pedersen; Thomas v O Hansen; Anne-Bine Skytte; Åke Borg; Christina Therkildsen

doi:10.1007/s10689-016-9875-7

BRCA1/BRA₂ founder mutations and cancer risks: impact in the western Danish population

Henriette Roed Nielsen, Mef Christina Nilbert, Janne Petersen, Steen Ladelund, Mads Thomassen, Inge Søkilde Pedersen, Thomas v O Hansen, Anne-Bine Skytte, Åke Borg, Christina Therkildsen

Section of Biostatistics

6 Citations (Scopus)

Abstract

Mutations in the BRCA1 and BRCA2 genes significantly contribute to hereditary breast cancer and ovarian cancer, but the phenotypic effect from different mutations is insufficiently recognized. We used a western Danish clinic-based cohort of 299 BRCA families to study the female cancer risk in mutation carriers and their untested first-degree relatives. Founder mutations were characterized and the risk of cancer was assessed in relation to the specific mutations. In BRCA1, the cumulative cancer risk at age 70 was 35 % for breast cancer and 29 % for ovarian cancer. In BRCA2, the cumulative risk was 44 % for breast cancer and 15 % for ovarian cancer. We identified 47 distinct BRCA1 mutations and 48 distinct mutations in BRCA2. Among these, 8 founder mutations [BRCA1 c.81-?_4986+?del, c.3319G>T (p.Glu1107*), c.3874delT and c.5213G>A (p.Gly1738Glu) and BRCA2 c.6373delA, c.7008-1G>A, c.7617+1G>A and c.8474delC] were found to account for 23 % of the BRCA1 mutations and for 32 % of the BRCA2 mutations. The BRCA1 mutation c.3319G>T was, compared to other BRCA1 mutations, associated with a higher risk for ovarian cancer. In conclusion, founder mutations in BRCA1 and BRCA2 contribute to up to one-third of the families in western Denmark and among these the BRCA1 c.3319G>T mutation is potentially linked to an increased risk of ovarian cancer.

Original language	English
Journal	Familial Cancer
Volume	15
Issue number	4
Pages (from-to)	507-512
Number of pages	6
ISSN	1389-9600
DOIs	https://doi.org/10.1007/s10689-016-9875-7
Publication status	Published - 1 Oct 2016

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@article{019db502b1fb41e48a1eb92b8847fd5b,

title = "BRCA1/BRA2 founder mutations and cancer risks: impact in the western Danish population",

abstract = "Mutations in the BRCA1 and BRCA2 genes significantly contribute to hereditary breast cancer and ovarian cancer, but the phenotypic effect from different mutations is insufficiently recognized. We used a western Danish clinic-based cohort of 299 BRCA families to study the female cancer risk in mutation carriers and their untested first-degree relatives. Founder mutations were characterized and the risk of cancer was assessed in relation to the specific mutations. In BRCA1, the cumulative cancer risk at age 70 was 35 % for breast cancer and 29 % for ovarian cancer. In BRCA2, the cumulative risk was 44 % for breast cancer and 15 % for ovarian cancer. We identified 47 distinct BRCA1 mutations and 48 distinct mutations in BRCA2. Among these, 8 founder mutations [BRCA1 c.81-?_4986+?del, c.3319G>T (p.Glu1107*), c.3874delT and c.5213G>A (p.Gly1738Glu) and BRCA2 c.6373delA, c.7008-1G>A, c.7617+1G>A and c.8474delC] were found to account for 23 % of the BRCA1 mutations and for 32 % of the BRCA2 mutations. The BRCA1 mutation c.3319G>T was, compared to other BRCA1 mutations, associated with a higher risk for ovarian cancer. In conclusion, founder mutations in BRCA1 and BRCA2 contribute to up to one-third of the families in western Denmark and among these the BRCA1 c.3319G>T mutation is potentially linked to an increased risk of ovarian cancer.",

author = "{Roed Nielsen}, Henriette and Nilbert, {Mef Christina} and Janne Petersen and Steen Ladelund and Mads Thomassen and Pedersen, {Inge S{\o}kilde} and Hansen, {Thomas v O} and Anne-Bine Skytte and {\AA}ke Borg and Christina Therkildsen",

year = "2016",

month = oct,

day = "1",

doi = "10.1007/s10689-016-9875-7",

language = "English",

volume = "15",

pages = "507--512",

journal = "Familial Cancer",

issn = "1389-9600",

publisher = "Springer",

number = "4",

}

TY - JOUR

T1 - BRCA1/BRA2 founder mutations and cancer risks

T2 - impact in the western Danish population

AU - Roed Nielsen, Henriette

AU - Nilbert, Mef Christina

AU - Petersen, Janne

AU - Ladelund, Steen

AU - Thomassen, Mads

AU - Pedersen, Inge Søkilde

AU - Hansen, Thomas v O

AU - Skytte, Anne-Bine

AU - Borg, Åke

AU - Therkildsen, Christina

PY - 2016/10/1

Y1 - 2016/10/1

N2 - Mutations in the BRCA1 and BRCA2 genes significantly contribute to hereditary breast cancer and ovarian cancer, but the phenotypic effect from different mutations is insufficiently recognized. We used a western Danish clinic-based cohort of 299 BRCA families to study the female cancer risk in mutation carriers and their untested first-degree relatives. Founder mutations were characterized and the risk of cancer was assessed in relation to the specific mutations. In BRCA1, the cumulative cancer risk at age 70 was 35 % for breast cancer and 29 % for ovarian cancer. In BRCA2, the cumulative risk was 44 % for breast cancer and 15 % for ovarian cancer. We identified 47 distinct BRCA1 mutations and 48 distinct mutations in BRCA2. Among these, 8 founder mutations [BRCA1 c.81-?_4986+?del, c.3319G>T (p.Glu1107*), c.3874delT and c.5213G>A (p.Gly1738Glu) and BRCA2 c.6373delA, c.7008-1G>A, c.7617+1G>A and c.8474delC] were found to account for 23 % of the BRCA1 mutations and for 32 % of the BRCA2 mutations. The BRCA1 mutation c.3319G>T was, compared to other BRCA1 mutations, associated with a higher risk for ovarian cancer. In conclusion, founder mutations in BRCA1 and BRCA2 contribute to up to one-third of the families in western Denmark and among these the BRCA1 c.3319G>T mutation is potentially linked to an increased risk of ovarian cancer.

AB - Mutations in the BRCA1 and BRCA2 genes significantly contribute to hereditary breast cancer and ovarian cancer, but the phenotypic effect from different mutations is insufficiently recognized. We used a western Danish clinic-based cohort of 299 BRCA families to study the female cancer risk in mutation carriers and their untested first-degree relatives. Founder mutations were characterized and the risk of cancer was assessed in relation to the specific mutations. In BRCA1, the cumulative cancer risk at age 70 was 35 % for breast cancer and 29 % for ovarian cancer. In BRCA2, the cumulative risk was 44 % for breast cancer and 15 % for ovarian cancer. We identified 47 distinct BRCA1 mutations and 48 distinct mutations in BRCA2. Among these, 8 founder mutations [BRCA1 c.81-?_4986+?del, c.3319G>T (p.Glu1107*), c.3874delT and c.5213G>A (p.Gly1738Glu) and BRCA2 c.6373delA, c.7008-1G>A, c.7617+1G>A and c.8474delC] were found to account for 23 % of the BRCA1 mutations and for 32 % of the BRCA2 mutations. The BRCA1 mutation c.3319G>T was, compared to other BRCA1 mutations, associated with a higher risk for ovarian cancer. In conclusion, founder mutations in BRCA1 and BRCA2 contribute to up to one-third of the families in western Denmark and among these the BRCA1 c.3319G>T mutation is potentially linked to an increased risk of ovarian cancer.

U2 - 10.1007/s10689-016-9875-7

DO - 10.1007/s10689-016-9875-7

M3 - Journal article

C2 - 26833046

SN - 1389-9600

VL - 15

SP - 507

EP - 512

JO - Familial Cancer

JF - Familial Cancer

IS - 4