Moderate-Risk Genes for Hereditary Ovarian Cancers Involved in the Homologous Recombination Repair Pathway

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2022 Oct 14

PMID 36233090

Authors

Akiko Abe

Issei Imoto

Arisa Ueki

Hidetaka Nomura

Hiroyuki Kanao

Affiliations

Soon will be listed here.

Abstract

Approximately 20% of cases of epithelial ovarian cancer (EOC) are hereditary, sharing many causative genes with breast cancer. The lower frequency of EOC compared to breast cancer makes it challenging to estimate absolute or relative risk and verify the efficacy of risk-reducing surgery in individuals harboring germline pathogenic variants (GPV) in EOC predisposition genes, particularly those with relatively low penetrance. Here, we review the molecular features and hereditary tumor risk associated with several moderate-penetrance genes in EOC that are involved in the homologous recombination repair pathway, i.e., , and . Understanding the molecular mechanisms underlying the expression and function of these genes may elucidate trends in the development and progression of hereditary tumors, including EOC. A fundamental understanding of the genes driving EOC can help us accurately estimate the genetic risk of developing EOC and select appropriate prevention and treatment strategies for hereditary EOC. Therefore, we summarize the functions of the candidate predisposition genes for EOC and discuss the clinical management of individuals carrying GPV in these genes.

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References

Putti S, Giovinazzo A, Merolle M, Falchetti M, Pellegrini M . ATM Kinase Dead: From Ataxia Telangiectasia Syndrome to Cancer. Cancers (Basel). 2021; 13(21). PMC: 8583659. DOI: 10.3390/cancers13215498. View

Neff R, Senter L, Salani R . mutation in ovarian cancer: testing, implications and treatment considerations. Ther Adv Med Oncol. 2017; 9(8):519-531. PMC: 5524247. DOI: 10.1177/1758834017714993. View

Huang R, Zhou P . DNA damage response signaling pathways and targets for radiotherapy sensitization in cancer. Signal Transduct Target Ther. 2020; 5(1):60. PMC: 7192953. DOI: 10.1038/s41392-020-0150-x. View

Yu W, Lescale C, Babin L, Bedora-Faure M, Lenden-Hasse H, Baron L . Repair of G1 induced DNA double-strand breaks in S-G2/M by alternative NHEJ. Nat Commun. 2020; 11(1):5239. PMC: 7567796. DOI: 10.1038/s41467-020-19060-w. View

Norquist B, Harrell M, Brady M, Walsh T, Lee M, Gulsuner S . Inherited Mutations in Women With Ovarian Carcinoma. JAMA Oncol. 2016; 2(4):482-90. PMC: 4845939. DOI: 10.1001/jamaoncol.2015.5495. View

Chiang Y, Lin P, Cheng W . Homologous Recombination Deficiency Assays in Epithelial Ovarian Cancer: Current Status and Future Direction. Front Oncol. 2021; 11:675972. PMC: 8551835. DOI: 10.3389/fonc.2021.675972. View

Matos-Rodrigues G, Guirouilh-Barbat J, Martini E, Lopez B . Homologous recombination, cancer and the 'RAD51 paradox'. NAR Cancer. 2021; 3(2):zcab016. PMC: 8209977. DOI: 10.1093/narcan/zcab016. View

Phelan C, Kuchenbaecker K, Tyrer J, Kar S, Lawrenson K, Winham S . Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer. Nat Genet. 2017; 49(5):680-691. PMC: 5612337. DOI: 10.1038/ng.3826. View

Cummings S, Roman S, Saam J, Bernhisel R, Brown K, Lancaster J . Age of ovarian cancer diagnosis among BRIP1, RAD51C, and RAD51D mutation carriers identified through multi-gene panel testing. J Ovarian Res. 2021; 14(1):61. PMC: 8086272. DOI: 10.1186/s13048-021-00809-w. View

10.

Tung N, Domchek S, Stadler Z, Nathanson K, Couch F, Garber J . Counselling framework for moderate-penetrance cancer-susceptibility mutations. Nat Rev Clin Oncol. 2016; 13(9):581-8. PMC: 5513673. DOI: 10.1038/nrclinonc.2016.90. View

11.

Zhang Y, Zhou J, Lim C . The role of NBS1 in DNA double strand break repair, telomere stability, and cell cycle checkpoint control. Cell Res. 2006; 16(1):45-54. DOI: 10.1038/sj.cr.7310007. View

12.

Syed A, Tainer J . The MRE11-RAD50-NBS1 Complex Conducts the Orchestration of Damage Signaling and Outcomes to Stress in DNA Replication and Repair. Annu Rev Biochem. 2018; 87:263-294. PMC: 6076887. DOI: 10.1146/annurev-biochem-062917-012415. View

13.

Vietri M, DElia G, Caliendo G, Casamassimi A, Federico A, Passariello L . Prevalence of mutations in BRCA and MMR genes in patients affected with hereditary endometrial cancer. Med Oncol. 2021; 38(2):13. PMC: 7826304. DOI: 10.1007/s12032-021-01454-5. View

14.

Domchek S, Robson M . Update on Genetic Testing in Gynecologic Cancer. J Clin Oncol. 2019; 37(27):2501-2509. PMC: 6754232. DOI: 10.1200/JCO.19.00363. View

15.

Suszynska M, Klonowska K, Jasinska A, Kozlowski P . Large-scale meta-analysis of mutations identified in panels of breast/ovarian cancer-related genes - Providing evidence of cancer predisposition genes. Gynecol Oncol. 2019; 153(2):452-462. DOI: 10.1016/j.ygyno.2019.01.027. View

16.

Zhou Z, Zeng F, Yuan J, Tang J, Colditz G, Tworoger S . Pelvic inflammatory disease and the risk of ovarian cancer: a meta-analysis. Cancer Causes Control. 2017; 28(5):415-428. PMC: 5616173. DOI: 10.1007/s10552-017-0873-3. View

17.

Ouhtit A, Gupta I, Shaikh Z . BRIP1, a potential candidate gene in development of non-BRCA1/2 breast cancer. Front Biosci (Elite Ed). 2015; 8(2):289-98. DOI: 10.2741/E767. View

18.

Rebbeck T, Lynch H, Neuhausen S, Narod S, Veer L, Garber J . Prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations. N Engl J Med. 2002; 346(21):1616-22. DOI: 10.1056/NEJMoa012158. View

19.

Bono M, Fanale D, Incorvaia L, Cancelliere D, Fiorino A, Calo V . Impact of deleterious variants in other genes beyond BRCA1/2 detected in breast/ovarian and pancreatic cancer patients by NGS-based multi-gene panel testing: looking over the hedge. ESMO Open. 2021; 6(4):100235. PMC: 8358413. DOI: 10.1016/j.esmoop.2021.100235. View

20.

Trabert B, Ness R, Lo-Ciganic W, Murphy M, Goode E, Poole E . Aspirin, nonaspirin nonsteroidal anti-inflammatory drug, and acetaminophen use and risk of invasive epithelial ovarian cancer: a pooled analysis in the Ovarian Cancer Association Consortium. J Natl Cancer Inst. 2014; 106(2):djt431. PMC: 3924755. DOI: 10.1093/jnci/djt431. View