; Ernst, Corinna
; Wappenschmidt, Barbara ; Niederacher, Dieter ; Weber-Lassalle, Konstantin ; Schmidt, Gunnar ; Hauke, Jan
; Quante, Anne S
; Weber-Lassalle, Nana ; Horváth, Judit ; Pohl-Rescigno, Esther ; Arnold, Norbert
; Rump, Andreas
; Gehrig, Andrea ; Hentschel, Julia ; Faust, Ulrike ; Dutrannoy, Véronique ; Meindl, Alfons ; Kuzyakova, Maria ; Wang-Gohrke, Shan ; Weber, Bernhard H. F ; Sutter, Christian ; Volk, Alexander E ; Giannakopoulou, Olga ; Lee, Andrew ; Engel, Christoph
; Schmidt, Marjanka K ; Antoniou, Antonis C ; Schmutzler, Rita K ; Kuchenbaecker, Karoline ; Hahnen, Eric | Item type: | Article | ||||
|---|---|---|---|---|---|
| Journal or Publication Title: | JNCI: Journal of the National Cancer Institute | ||||
| Publisher: | Oxford Univ. Press | ||||
| Place of Publication: | CARY | ||||
| Volume: | 113 | ||||
| Number of Issue or Book Chapter: | 7 | ||||
| Page Range: | pp. 893-899 | ||||
| Date: | 2020 | ||||
| Institutions: | Medicine > Lehrstuhl für Humangenetik | ||||
| Identification Number: |
| ||||
| Keywords: | GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; PREVENTION; COGS; | ||||
| Dewey Decimal Classification: | 600 Technology > 610 Medical sciences Medicine | ||||
| Status: | Published | ||||
| Refereed: | Yes, this version has been refereed | ||||
| Created at the University of Regensburg: | Yes | ||||
| Item ID: | 56563 |
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 ...

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.
Metadata last modified: 29 Feb 2024 12:28
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