Abstract P5-09-11: Direct-to-consumer genetic testing as an alternative model for identifying BRCA carriers
Authors: Tennen R , Laskey S , Koelsch B , McIntyre M , Greb A , Kim E , Tung J 
Published: May 2019

Background: Three BRCA1 and BRCA2 founder variants (185delAG, 5382insC, and 6174delT) are common in the Ashkenazi Jewish population. Our objective was to use data collected by direct-to-consumer (DTC) genetic testing (23andMe, Inc., Mountain View CA) to determine the frequency of these variants in a generally unselected group of genotyped individuals and to characterize the cohort of individuals carrying one of these variants in terms of self-reported ancestry, genetic ancestry, and personal and family history of cancer.

Methods: Individuals were genotyped prior to November 2017 on one of four custom Illumina genotyping arrays, which included the three Ashkenazi founder variants. Ashkenazi Jewish genetic ancestry was calculated by an analysis of local ancestry. Self-reported data from customer surveys on ancestry and personal and family history of cancer was used in the analysis. Inclusion criteria were 23andMe customers who were 18 years or older and consented to participate in research. IRB approval was obtained from Ethical & Independent Review Services.

Results: More than 80% of individuals consented to participate in online research. 2,853 carriers of at least one Ashkenazi Jewish founder variant were identified out of 1,980,076 eligible participants. 54% (1,539) were males; 46% (1,314) were females; 86% (2,462) were over 30 years of age. 249 (9%) had no detectable Ashkenazi Jewish genetic ancestry. 1,967/2,853 (69%) provided self-reported ancestry information. 415/1,967 (21%) did not self-report Jewish ancestry but of those, 258 (62%) had at least 1% Ashkenazi Jewish genetic ancestry. Individuals with less than 20% Ashkenazi Jewish genetic ancestry were less than 50% likely to report having Jewish ancestry.

Self-reported vs. genetic ancestry information No detectable Ashkenazi Jewish genetic ancestry&gt;1% detectable Ashkenazi Jewish genetic ancestryTotalSelf reported Jewish ancestry9 (1%)1,543 (99%)1552Self reported no Jewish ancestry157 (38%)258 (62%)415Total16618011967

1,837 participants provided personal cancer history information and 393 provided first-degree family history information. 1,435/1,837 (78%) reported no personal history of breast, ovarian, pancreatic, or prostate cancer. 44% (172/393) reported no first-degree family history of breast, ovarian, pancreatic, or prostate cancer.

Conclusions: This is the first description of a large, unselected cohort of BRCA carriers identified through DTC genetic testing. 21% of carriers in our cohort did not self-report Jewish ancestry despite more than half of those having detectable Ashkenazi Jewish genetic ancestry. Even though personal or family history was only available for a subset, many did not report suggestive histories of breast, ovarian, prostate, or pancreatic cancer. Although there are limitations to the data set, these findings suggest the need for alternative models for identifying carriers of specified BRCA variants who may not otherwise be identified for genetic testing. Additionally, the number of males identified underscores the importance of male carriers in cancer genetic risk assessment.

Citation Format: Tennen R, Laskey S, Koelsch B, McIntyre M, Greb A, Kim E, Tung J. Direct-to-consumer genetic testing as an alternative model for identifying BRCA carriers [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-09-11.