Abstract
BRCA1- and BRCA2-associated hereditary breast and ovarian cancer syndromes are among the best-known and most extensively studied hereditary cancer syndromes. Nevertheless, many patients who proved negative at BRCA genetic testing bring pathogenic mutations in other suppressor genes and oncogenes associated with hereditary breast and/or ovarian cancers. These genes include TP53 in Li–Fraumeni syndrome, PTEN in Cowden syndrome, mismatch repair (MMR) genes in Lynch syndrome, CDH1 in diffuse gastric cancer syndrome, STK11 in Peutz–Jeghers syndrome, and NF1 in neurofibromatosis type 1 syndrome. To these, several other genes can be added that act jointly with BRCA1 and BRCA2 in the double-strand break repair system, such as PALB2, ATM, CHEK2, NBN, BRIP1, RAD51C, and RAD51D. Management of primary and secondary cancer prevention in these hereditary cancer syndromes is crucial. In particular, secondary prevention by screening aims to discover precancerous lesions or cancers at their initial stages because early detection could allow for effective treatment and a full recovery. The present review aims to summarize the available literature and suggest proper screening strategies for hereditary breast and/or ovarian cancer syndromes other than BRCA.
Highlights
In hereditary cancer syndromes (HCSs), inherited mutations lead to an increased risk of developing certain tumors, frequently at an earlier age than in the rest of the population [1]
Elevated cancer risk is usually due to a mutation in a single gene involved in cell cycle regulation or in DNA damage repair mechanisms (Figure 1). e most widely known HCSs include hereditary breast and ovarian cancer syndromes due to mutations in the BRCA1/2 genes [2, 3], Li–Fraumeni syndrome due to mutations in TP53 [4], Cowden syndrome due to mutations in PTEN [5], Lynch syndrome, in which mutations in the DNA mismatch repair system are involved [6, 7], diffuse gastric cancer syndrome caused by CDH1 gene mutation [8], Peutz–Jeghers syndrome caused by mutations in the STK11 [9] gene, and neurofibromatosis type 1 syndrome caused by NF1 mutations [10]
Pathogenic alterations in PALB2 [11], ATM [12], CHEK2 [13], and NBN [14] are correlated with an increased risk for breast cancer and/or other cancers, whereas other genes such as BRIP1, RAD51C, and RAD51D are associated with an increased ovarian cancer risk [15]
Summary
In hereditary cancer syndromes (HCSs), inherited mutations lead to an increased risk of developing certain tumors, frequently at an earlier age than in the rest of the population [1]. E most widely known HCSs include hereditary breast and ovarian cancer syndromes due to mutations in the BRCA1/2 genes [2, 3], Li–Fraumeni syndrome due to mutations in TP53 [4], Cowden syndrome due to mutations in PTEN [5], Lynch syndrome, in which mutations in the DNA mismatch repair system are involved [6, 7], diffuse gastric cancer syndrome caused by CDH1 gene mutation [8], Peutz–Jeghers syndrome caused by mutations in the STK11 [9] gene, and neurofibromatosis type 1 syndrome caused by NF1 mutations [10]. Is review aims to summarize the available literature and suggest proper screening strategies for hereditary breast and/or ovarian cancer syndromes other than those associated with BRCA mutations
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