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. 2016 Feb;24(2):258-62.
doi: 10.1038/ejhg.2015.108. Epub 2015 May 27.

High prevalence of BRCA1 stop mutation c.4183C>T in the Tyrolean population: implications for genetic testing

Laura Pölsler  1 , Heidi Fiegl  2 , Katharina Wimmer  1 , Willi Oberaigner  3   4 , Albert Amberger  1 , Pia Traunfellner  1 , Raphael J Morscher  1   5 , Ingrid Weber  1 , Christine Fauth  1 , Annekatrin Wernstedt  1 , Barbara Sperner-Unterweger  6 , Anne Oberguggenberger  6 , Michael Hubalek  2 , Christian Marth  2 , Johannes Zschocke  1
Affiliations

High prevalence of BRCA1 stop mutation c.4183C>T in the Tyrolean population: implications for genetic testing

Laura Pölsler et al. Eur J Hum Genet. 2016 Feb.

Abstract

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.4183C>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.

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Figures

Figure 1
Figure 1
(a) Number and distribution of breast cancer cases genotyped for the BRCA1 mutation c.4183C>T in the North Tyrol. (b) Number and distribution of ovarian cancer cases genotyped for the BRCA1 mutation c.4183C>T in the North Tyrol. Grey outline: the Austrian federal state of the Tyrol; red outline: the Lower Inn Valley region (districts Schwaz and Kufstein). Filled parts of circles: number of cases without the mutation. Hatched parts of circles: number of mutation carriers.
See this image and copyright information in PMC

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