TY - JOUR
T1 - High prevalence of BRCA1 stop mutation c.4183C>T in the Tyrolean population
T2 - implications for genetic testing
AU - Poelsler, Laura
AU - Fiegl, Heidi
AU - Wimmer, Katharina
AU - Oberaigner, Willi
AU - Amberger, Albert
AU - Traunfellner, Pia
AU - Morscher, Raphael J.
AU - Weber, Ingrid
AU - Fauth, Christine
AU - Wernstedt, Annekatrin
AU - Sperner-Unterweger, Barbara
AU - Oberguggenberger, Anne
AU - Hubalek, Michael
AU - Marth, Christian
AU - Zschocke, Johannes
N1 - Morscher RJ: Research Programme for Receptor Biochemistry and Tumour Metabolism, Paracelsus Medical University, Salzburg, Austria.
PY - 2016/2
Y1 - 2016/2
N2 - Screening for founder mutations in BRCA1 and BRCA2 has been discussed as a cost-effective testing strategy in certain populations. In this study, comprehensive BRCA1 and BRCA2 testing was performed in a routine diagnostic setting. The prevalence of the BRCA1 stop mutation c.4183C4>T, p.(Gln1395Ter), was determined in unselected breast and ovarian cancer patients from different regions in the Tyrol. Cancer registry data were used to evaluate the impact of this mutation on regional cancer incidence. The mutation c.4183C>T was detected in 30.4% of hereditary BRCA1-associated breast and ovarian cancer patients in our cohort. It was also identified in 4.1% of unselected (26% of unselected triple negative) Tyrolean breast cancer patients and 6.8% of unselected ovarian cancer patients from the Lower Inn Valley (LIV) region. Cancer incidences showed a region-specific increase in age-stratified breast and ovarian cancer risk with standardized incidence ratios of 1.23 and 2.13, respectively. We, thus, report a Tyrolean BRCA1 founder mutation that correlates to a local increase in the breast and ovarian cancer risks. On the basis of its high prevalence, we suggest that targeted genetic analysis should be offered to all women with breast or ovarian cancer and ancestry from the LIV region.
AB - Screening for founder mutations in BRCA1 and BRCA2 has been discussed as a cost-effective testing strategy in certain populations. In this study, comprehensive BRCA1 and BRCA2 testing was performed in a routine diagnostic setting. The prevalence of the BRCA1 stop mutation c.4183C4>T, p.(Gln1395Ter), was determined in unselected breast and ovarian cancer patients from different regions in the Tyrol. Cancer registry data were used to evaluate the impact of this mutation on regional cancer incidence. The mutation c.4183C>T was detected in 30.4% of hereditary BRCA1-associated breast and ovarian cancer patients in our cohort. It was also identified in 4.1% of unselected (26% of unselected triple negative) Tyrolean breast cancer patients and 6.8% of unselected ovarian cancer patients from the Lower Inn Valley (LIV) region. Cancer incidences showed a region-specific increase in age-stratified breast and ovarian cancer risk with standardized incidence ratios of 1.23 and 2.13, respectively. We, thus, report a Tyrolean BRCA1 founder mutation that correlates to a local increase in the breast and ovarian cancer risks. On the basis of its high prevalence, we suggest that targeted genetic analysis should be offered to all women with breast or ovarian cancer and ancestry from the LIV region.
KW - Ovarian-cancer families
KW - Breast-cancer
KW - Hereditary breast
KW - Founder mutations
KW - Frequency
UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=pmu_pure&SrcAuth=WosAPI&KeyUT=WOS:000370469400016&DestLinkType=FullRecord&DestApp=WOS
U2 - 10.1038/ejhg.2015.108
DO - 10.1038/ejhg.2015.108
M3 - Original Article
C2 - 26014432
SN - 1018-4813
VL - 24
SP - 258
EP - 262
JO - EUROPEAN JOURNAL OF HUMAN GENETICS
JF - EUROPEAN JOURNAL OF HUMAN GENETICS
IS - 2
ER -