Hereditary Cancers

It is estimated that 3–5% of all human cancers follow autosomal Mendelian pattern of inheritance, and up to 10% cancer cases have a family history of cancer or other features that merit specialized genetic risk assessment, genetic counseling and germline genetic testing. The five-tier classification of gene variants, the cumulative cancer risk and genotype–phenotype correlation associated with pathogenic or likely pathogenic variants in different cancer predisposition genes are described. The criteria and process of genetic risk assessment and pathognomonic features of certain syndromes are discussed. The indications of germline genetic testing continue to expand both for identifying inherited cancer risk and for precision oncology based on identification of germline mutations in DNA repair genes. Important clinical, genetic and ethical aspects of inherited cancer predisposition, genetic counseling and testing are described for practicing oncologists who are in the transition phase toward mainstreaming of genetic testing. Strategies for prevention and early detection of breast, ovary, colorectal, thyroid and other cancers are described.