BRCA1/BRA2 founder mutations and cancer risks: impact in the western Danish population
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BRCA1/BRA2 founder mutations and cancer risks : impact in the western Danish population. / Roed Nielsen, Henriette; Nilbert, Mef Christina; Petersen, Janne; Ladelund, Steen; Thomassen, Mads; Pedersen, Inge Søkilde; Hansen, Thomas v O; Skytte, Anne-Bine; Borg, Åke; Therkildsen, Christina.
In: Familial Cancer, Vol. 15, No. 4, 10.2016, p. 507-512.Research output: Contribution to journal › Journal article › Research › peer-review
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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
Y1 - 2016/10
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
VL - 15
SP - 507
EP - 512
JO - Familial Cancer
JF - Familial Cancer
SN - 1389-9600
IS - 4
ER -
ID: 164817864