Hereditary Ovarian Cancer: Not OnlyBRCA1 and 2 Genes

Abstract

More than one-fifth of ovarian tumors have hereditary susceptibility and, in about 65–85% of these cases, the genetic abnormality is a germline mutation in BRCA genes. Nevertheless, several other suppressor genes and oncogenes have been associated with hereditary ovarian cancers, including the mismatch repair (MMR) genes in Lynch syndrome, the tumor suppressor gene, TP53, in the Li-Fraumeni syndrome, and several other genes involved in the double-strand breaks repair system, such as CHEK2, RAD51, BRIP1, and PALB2. The study of genetic discriminators and deregulated pathways involved in hereditary ovarian syndromes is relevant for the future development of molecular diagnostic strategies and targeted therapeutic approaches. The recent development and implementation of next-generation sequencing technologies have provided the opportunity to simultaneously analyze multiple cancer susceptibility genes, reduce the delay and costs, and optimize the molecular diagnosis of hereditary tumors. Particularly, the identification of mutations in ovarian cancer susceptibility genes in healthy women may result in a more personalized cancer risk management with tailored clinical and radiological surveillance, chemopreventive approaches, and/or prophylactic surgeries. On the other hand, for ovarian cancer patients, the identification of mutations may provide potential targets for biologic agents and guide treatment decision-making.

Body weight, hemoglobin, and absolute neutrophil count in patients with advanced-stage epithelial ovarian cancer who received chemotherapy: A single-center study

“…Early examination should be performed in individuals with a family history of malignancy. Thus, proactive steps can be taken for early detection, timely treatment, and improved prognosis in patients with ovarian cancer [22]. Decreases in body weight and BMI were observed in patients in the present study.…”

O-Glcnac Glycosylation of Rad51 Plays an Important Role in Promoting Colorectal Cancer Cell Invasion

“…In addition, domestic and foreign researchers also found that gene polymorphism of Rad51 recognized as the risk factor of CRC carcinogenesis. At present, more studies are focusing on the 135G/C single nucleotide polymorphism of Rad51 gene, the allelic variation is regarded as a susceptible factor for CRC, but the exact mechanism is not yet clear, which may be related to the presence of a BRCA2 mutation [19]. In contrast, researches on the correlation between Rad51 and tumor metastasis are still insufficient.…”

Ovarian Cancer Prevention in High-risk Women

“…The MMR system works to remove single-strand breaks from DNA by recognizing and correcting short insertions and deletions and single base pair mismatches. When these MMR genes are mutated areas of sequence repeats, microsatellites, can change in size which causes frameshift mutations and DNA instability (31). The overall lifetime risk of ovarian cancer for women with Lynch syndrome is estimated at 8-12% (30-32).…”

“…Using this technology additional inherited genes implicated in ovarian cancer have been identified (11, 14, 24, 31, 40). Panel testing among a high risk population, will identify pathogenic mutations in moderate or high penetrance genes (other than BRCA1/2 ) in 3.8% of women (41).…”

“…Mutations in RAD51C and RAD51D are the most common of these genes and found in 1.5-4% and 0.9% of highly penetrant breast and ovarian cancer families conferring a moderate ovarian cancer risk susceptibility (11, 14, 24). In addition, BRIP1 and BARD1 have roles in repair of DNA damage checkpoint control and have been shown to correlate with moderate ovarian cancer susceptibility that may warrant their use in routine clinical genetic testing(24, 31). Genes with other biological roles including SK11, PTEN, CDH1 and NF1 have also been implicated in increased ovarian cancer risk(24).…”