Population-based screening for breast and ovarian cancer risk due to BRCA1 and BRCA2

The objection to offering BRCA testing to everyone in a population was that the risk figures came from families referred to cancer genetics clinics, who are selected for having a lot of cancer. Ephrat Levy-Lahad and Mary-Claire King's answer was to start somewhere with no such selection. Between June 2004 and December 2010 they recruited healthy Ashkenazi Israeli men aged 30 and over with no personal history of cancer from health-screening centres and outpatient clinics: 8,222 enrolled, 8,195 (99.7 percent) were successfully genotyped for the three founder variants. Female relatives of the carriers were then enrolled and genotyped.

Carrier frequency was 1.14 percent for BRCA1 and 1.03 percent for BRCA2, 2.17 percent combined. Among fully genotyped sibships, cumulative risk of breast or ovarian cancer was 0.60 by age 60 and 0.83 by age 80 for BRCA1 carriers, and 0.33 by 60 and 0.76 by 80 for BRCA2 carriers. Risk was higher in later birth cohorts: 3.8-fold higher age-specific risk for carriers born after 1958 than for those born in or before it.

The decisive number for policy is that 51 percent of the 167 carrier families had little or no relevant cancer history, so testing triggered by family history would have missed them; and only 35 percent of the 82 families that did have a high cancer burden had ever been referred for genetic counselling, in a country with universal health coverage. Israel began offering the three-variant test to every woman of Ashkenazi origin in January 2020.