Ten modifiers of BRCA1 penetrance validated in a Norwegian series

Abstract

BackgroundCommon genetic variants have been shown to modify BRCA1 penetrance. The aim of this study was to validate these reports in a special cohort of Norwegian BRCA1 mutation carriers that were selected for their extreme age of onset of disease.MethodsThe ten variants rs13387042, rs3803662, rs8170, rs9397435, rs700518, rs10046, rs3834129, rs1045485, rs2363956 and rs16942 were selected to be tested on samples from our biobank. We selected female BRCA1 mutation carriers having had a diagnosis of breast or ovarian cancer below 40 years of age (young cancer group, N = 40), and mutation carriers having had neither breast nor ovarian cancer above 60 years of age (i.e., old no cancer group, N = 38). Relative risks and odd ratios of belonging to the young cancer versus old no cancer groups were calculated as a function of having or not having the SNPs in question.ResultsFive of the ten variants were found to be significantly associated with early onset cancer. Some of the variation between our results and those previously reported may be ascribed to stochastic effects in our limited number of patient studies, and/or genetic drift in linkage disequilibrium in the genetically isolated Norwegian population. This is in accordance with the understanding that the SNPs are markers in linkage disequilibrium with their respective disease-causing genetic variants, and that this may vary between different populations.ConclusionsThe results confirmed associations previously reported, with the notion that the degree of association may differ between other populations, which must be considered when discussing the clinical use of the associations described.Electronic supplementary materialThe online version of this article (doi:10.1186/s13053-015-0035-0) contains supplementary material, which is available to authorized users.

Haplotypes of single cancer driver genes and their local ancestry in a highly admixed long-lived population of Northeast Brazil

“…, 2015 ; Ríos-Tamayo et al , 2016 ; Oh et al, 2017a ; Tong et al., 2018 ) rs11651052 ( Painter et al , 2015 ). Endometrial cancer risk rs11658063 ( Jones et al, 2019 ) CAG (10.8%) -0.95 72.4 0.606 0.9-0.98 TA C (31.5%) -0.96 79.96 0.688 0.92-0.99 TAG (6,8%) -0.95 51.56 0.453 0.89-0.99 BRCA1 TG (69.2%) rs16942 rs1799949 -0.99 101.43 0.868 0.96-1.0 rs16942 ( Cox et al , 2011 ; Heramb et al. , 2015 ; Sagna et al, 2019 ) rs1799949 ( Ricks-Santi et al , 2017 ).…”