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Comment
. 2020 Jul 16;383(3):286-288.
doi: 10.1056/NEJMc1913988.

Etiologic Index - A Case-Only Measure of BRCA1/2-Associated Cancer Risk

Raymond Hughley  1 , Rosa Karlic  2 , Himanshu Joshi  1 , Clare Turnbull  3 , William D Foulkes  4 , Paz Polak  1
Affiliations
Comment

Etiologic Index - A Case-Only Measure of BRCA1/2-Associated Cancer Risk

Raymond Hughley et al. N Engl J Med. .
No abstract available

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Figures

Figure 1.
Figure 1.. Excess of Risk and the Etiologic Index for BRCA1/2 across Cancer Types.
Shown are the allelic fractions and etiologic indexes for tumors with germline pathogenic variants (GPVs) in BRCA1 (Panel A) and BRCA2 (Panel B). The tumors containing GPVs are categorized into three groups: those without second hits (monoallelic fraction), those accompanied by second somatic hits (biallelic fraction), and those for which, because of technical issues, it is not possible to determine whether the GPVs are accompanied by loss of heterozygosity (LOH) (germline with indeterminate LOH status). The tumors are grouped according to the strength of their association with BRCA1/2 GPVs: breast, ovarian, prostate, and pancreatic cancers are termed “established.” The established group represents the combination of these four tumors, whereas the “nonestablished” group includes all the patients with other tumors in the data set (52 different tumor types). The prevalence of monoallelic status for BRCA1 and BRCA2 in patient tumors is close to the estimated GPV prevalence of 0.0037 for BRCA1 heterozygotes (dashed line in Panel A) and 0.0051 for BRCA2 heterozygotes (dashed line in Panel B). These numbers are based on the weighted average of prevalences: 80% of the alleles occur at a prevalence of 1 in 190 for BRCA1/2 (the prevalence in Pennsylvania), with 65% of the GPVs occurring in BRCA2 and 35% in BRCA1, and 20% of the alleles are from the Ashkenazi Jewish population (prevalence of 1 in 40 of BRCA1/2) with the assumption that the GPVs are split evenly between BRCA1 and BRCA2. This weighted average reflects the patient population at Memorial Sloan Kettering Cancer Center, where the study was performed. The etiologic index is defined as the sum of the prevalence of biallelic and monoallelic events divided by the prevalence of monoallelic events. The etiologic indexes derived from this method are close to those estimated from epidemiologic studies.,
See this image and copyright information in PMC

Comment on

  • Tumour lineage shapes BRCA-mediated phenotypes.
    Jonsson P, Bandlamudi C, Cheng ML, Srinivasan P, Chavan SS, Friedman ND, Rosen EY, Richards AL, Bouvier N, Selcuklu SD, Bielski CM, Abida W, Mandelker D, Birsoy O, Zhang L, Zehir A, Donoghue MTA, Baselga J, Offit K, Scher HI, O'Reilly EM, Stadler ZK, Schultz N, Socci ND, Viale A, Ladanyi M, Robson ME, Hyman DM, Berger MF, Solit DB, Taylor BS. Jonsson P, et al. Nature. 2019 Jul;571(7766):576-579. doi: 10.1038/s41586-019-1382-1. Epub 2019 Jul 10. Nature. 2019. PMID: 31292550 Free PMC article.

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