As actionable mutations may change cancer treatment and also cancer screening and prevention, genetic testing is important for patients with and without personal history of cancer. While testing for oncologic patients are increasingly more expanded, universal, accessible and affordable; the value of population-based testing is unknown.


This is a pilot study formed by 2 cohorts of participants residing in San Francisco Bay Area: multi-ethnic sample (cohort 1) and Jewish community members from a diverse ethnic and geographic background (cohort 2). After consent, germline 30-gene cancer risk panel was offered to planned 500 participants of each cohort. Participants were older than 21 and without a known family mutation.


991 participants completed testing. 29/496 (5.85%) and 68/495 (13.73%) were found to have a heterozygous cancer risk variant in cohort 1 and 2, respectively. The majority of these have been in high or moderate cancer susceptibility genes: APC (0.8% and 7.5%), BRCA1 (0.4% and 0.61%), BRCA2 (0.4% and 1.21%), BRIP1 (0.4% and 0%), CHEK2 (1.0% and 3.23%), MUTYH (1.4% and 0.4%), PALB2 (0.2% and 0%), PMS2 (0.2% and 0%) and TP53 (0% and 0.4%). All 37 APC variants and 15 of 16 CHEK2 variants in cohort 2 were the low penetrance Ashkenazi Jewish founder variants: APC I1307K and CHEK2 S428F. The rate of variant of unknown significance differed significantly among the 2 cohorts (24.8% vs 11.3%) and among the ethnic groups in cohort 1 (19.1% in europeans vs. 29.9% in non-europeans).


This innovative pilot study demonstrates that large population screening of cancer susceptibility variants is feasible and awareness about testing can be successfully raised in local communities. This model may be a plausible way to identify high-risk individuals and better serve them in the era of personalized medicine and precision management.