Risks of Solid Tumors in Heterozygous Carriers of Recessive Syndromes

Česká verzia

Authors: Monika Koudová; Alena Puchmajerová
Authors place of work: Centrum lékařské genetiky a reprodukční medicíny GENNET, Praha
Published in the journal: Klin Onkol 2019; 32(Supplementum2): 14-23
Category: Přehled
doi: https://doi.org/10.14735/amko2019S14

Summary

Expanded gene panel testing for hereditary cancer predispositions using massive parallel sequencing can identify heterozygous pathogenic variants of genes that cause autosomal recessive inherited cancer syndromes. There are no clinical guidelines regarding assessment of the risk of developing solid tumors or for developing appropriate surveillance strategies for heterozygotes for most of these genes, nor is there delineation with respect to the management for genetic testing of relatives and partners. Based on current knowledge, our aim was to create “Czech guidelines” for these cases. Here, we present an overview of the selected genes for autosomal recessive inherited tumor syndromes. The genes were divided into two groups: genes causing Fanconi anemia and genes causing other autosomal recessive inherited tumor syndromes. A summary table was created for each group. The table shows the population frequency of heterozygotes, the cancer risk for heterozygotes, the proposed surveillance strategy, and recommendations for family prediction and genetic testing of partners. Predictive testing should be performed in the case of heterozygotes that have an increased risk of cancer and/or as prerequisite to further reproduction of heterozygotes for a given gene with significant population frequency (this allows an estimation of the risk of autosomal recessive syndrome for children of heterozygote for mutation). These suggestions and recommendations are based on current knowledge and would need to be further corrected in the future based on increasing knowledge of existing or as-yet-unidentified genes.

The authors thank to all the staff of the Molecular Genetic Laboratory of the GENNET

Medical Genetics and Reproductive Medicine Center for their cooperation.

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.
Submitted: 21. 3. 2019

Accepted: 2. 5. 2019

Keywords:

Mutation – hereditary cancer syndromes – autozomal recessive inheritance – heterozygote – risk of cancer – predictive testing

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