Risk of cancer in heterozygous relatives of patients with Fanconi anemia

Genet Med. 2022 Jan;24(1):245-250. doi: 10.1016/j.gim.2021.08.013. Epub 2021 Nov 30.


Purpose: Fanconi anemia (FA) is a cancer-prone inherited bone marrow failure syndrome caused by biallelic pathogenic variants in one of >22 genes in the FA/BRCA DNA repair pathway. A major concern is whether the risk of cancer is increased in individuals with a single pathogenic FA gene variant.

Methods: We evaluated the risk of cancer in the relatives of patients with FA in the National Cancer Institute Inherited Bone Marrow Failure Syndrome cohort. We genotyped all available relatives and determined the rates, types of cancer and the age of patients at cancer diagnosis. We calculated the observed-to-expected (O/E) cancer ratios using data from the Surveillance, Epidemiology, and End Results Program adjusted for age, sex, and birth cohort.

Results: The risk of cancer was not increased among all FA relatives and FA heterozygotes (O/E ratios of 0.78 and 0.79, respectively). In particular, the risk of cancer was not increased among FANCA or FANCC heterozygotes (O/E ratios of 0.92 and 0.71, respectively). Relatives did not have typical FA cancers, and age at cancer diagnosis was not younger than expected.

Conclusion: Understanding the risk of cancer in individuals with single pathogenic FA variants is critical for counseling and management. We did not find increased risk of cancer in these individuals. These findings do not extend to the known cancer predisposition autosomal dominant FA genes, namely BRCA1, BRCA2, PALB2, BRIP1, and RAD51C.

Keywords: Cancer; Fanconi anemia; Heterozygotes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Fanconi Anemia* / epidemiology
  • Fanconi Anemia* / genetics
  • Fanconi Anemia* / pathology
  • Genetic Predisposition to Disease
  • Genotype
  • Heterozygote
  • Humans
  • Neoplasms* / epidemiology
  • Neoplasms* / genetics