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Erschienen in:
02.06.2020 | Epidemiology
Frequency of heterozygous germline pathogenic variants in genes for Fanconi anemia in patients with non-BRCA1/BRCA2 breast cancer: a meta-analysis
Erschienen in: Breast Cancer Research and Treatment | Ausgabe 2/2020
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Purpose
Germline pathogenic variants in BRCA1 (FANCD1) and BRCA2 (FANCS) do not explain all familial or sporadic cases with breast cancer. Several reports indicate a role for pathogenic variants in other genes in the Fanconi anemia/breast cancer DNA repair pathway; the strengths of these associations vary widely. Publications from 2006 through 2017 were reviewed to provide a better estimate of the role of pathogenic variants in genes in this pathway in breast cancer.
Methods
We identified cohorts and case–control reports describing heterozygous pathogenic variants in Fanconi anemia genes in breast cancer cases with high risk of a germline pathogenic variant in a non-BRCA1/2 breast cancer susceptibility gene (“familial”), and cases unselected for family history (“unselected”). Meta-analysis and meta-regression were used to estimate the frequencies of pathogenic variants in cohorts and the odds ratios (OR) in case–control studies.
Results
Meta-analysis of more than 100 reports of FANCN/PALB2 in familial breast cancer cases provided an overall pathogenic variant prevalence of 1.29% and an OR of 8.45. The prevalence in unselected cohorts was 0.64%, and the OR was 4.76. Pathogenic variants in FANCJ/BRIP1 had a prevalence of 0.5% in familial cases, and an OR of 1.62; their prevalence in unselected cases was 0.39%. FANCO/RAD51C, FANCP/SLX4, FANCU/XRCC2, FANCD2, and other FA-related genes all had prevalences of ≤ 0.5% among familial cases, and even lower in unselected cases.
Conclusions
Heterozygous pathogenic variants in FANCN/PALB2 and possibly FANCJ/BRIP1 may account for 1–2% of familial non-BRCA1/2 breast cancer cases and 0.5–1% of unselected cases. Genetic counseling and testing may be suggested for unaffected relatives.