Borde, Julika and Ernst, Corinna and Wappenschmidt, Barbara and Niederacher, Dieter and Weber-Lassalle, Konstantin and Schmidt, Gunnar and Hauke, Jan and Quante, Anne S. and Weber-Lassalle, Nana and Horvath, Judit and Pohl-Rescigno, Esther and Arnold, Norbert and Rump, Andreas and Gehrig, Andrea and Hentschel, Julia and Faust, Ulrike and Dutrannoy, Veronique and Meindl, Alfons and Kuzyakova, Maria and Wang-Gohrke, Shan and Weber, Bernhard H. F. and Sutter, Christian and Volk, Alexander E. and Giannakopoulou, Olga and Lee, Andrew and Engel, Christoph and Schmidt, Marjanka K. and Antoniou, Antonis C. and Schmutzler, Rita K. and Kuchenbaecker, Karoline and Hahnen, Eric (2021) Performance of Breast Cancer Polygenic Risk Scores in 760 Female CHEK2 Germline Mutation Carriers. JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 113 (7): djaa203. pp. 893-899. ISSN 0027-8874, 1460-2105
Full text not available from this repository. (Request a copy)Abstract
Background: Genome-wide association studies suggest that the combined effects of breast cancer (BC)-associated single nucleotide polymorphisms (SNPs) can improve BC risk stratification using polygenic risk scores (PRSs). The performance of PRSs in genome-wide association studies-independent clinical cohorts is poorly studied in individuals carrying mutations in moderately penetrant BC predisposition genes such as CHEK2. Methods: A total of 760 female CHEK2 mutation carriers were included; 561 women were affected with BC, of whom 74 developed metachronous contralateral BC (mCBC). For PRS calculations, 2 SNP sets covering 77 (SNP set 1, developed for BC risk stratification in women unselected for their BRCA1/2 germline mutation status) and 88 (SNP set 2, developed for BC risk stratification in female BRCA1/2 mutation carriers) BC-associated SNPs were used. All statistical tests were 2-sided. Results: Both SNP sets provided concordant PRS results at the individual level (r = 0.91, P < 2.20 x 10(-16)). Weighted cohort Cox regression analyses revealed statistically significant associations of PRSs with the risk for first BC. For SNP set 1, a hazard ratio of 1.71 per SD of the PRS was observed (95% confidence interval =1.36 to 2.15, P = 3.87 x 10(-6)). PRSs identify a subgroup of CHEK2 mutation carriers with a predicted lifetime risk for first BC that exceeds the surveillance thresholds defined by international guidelines. Association of PRS with mCBC was examined via Cox regression analysis (SNP set 1 hazard ratio = 1.23, 95% confidence interval = 0.86 to 1.78, P = .26). Conclusions: PRSs may be used to personalize risk-adapted preventive measures for women with CHEK2 mutations. Larger studies are required to assess the role of PRSs in mCBC predisposition.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; PREVENTION; COGS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Humangenetik |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 21 Sep 2022 09:19 |
| Last Modified: | 21 Sep 2022 09:19 |
| URI: | https://pred.uni-regensburg.de/id/eprint/47825 |
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