Hereditary cancer syndromes with high risk of endometrial and ovarian cancer: Surgical options for personalized care

BackgroundHereditary cancer syndromes (HCS) are responsible for 5-10% of cancer cases. Genetic testing to identify pathogenic variants associated with cancer predisposition has not been routinely available in Vietnam. Consequently, the prevalence and genetic landscape of HCS remain unknown.Methods1165 Vietnamese individuals enrolled in genetic testing at our laboratory in 2020. We performed analysis of germline mutations in 17 high- and moderate- penetrance genes associated with HCS by next generation sequencing.ResultsA total of 41 pathogenic variants in 11 genes were detected in 3.2% individuals. The carrier frequency was 4.2% in people with family or personal history of cancer and 2.6% in those without history. The percentage of mutation carriers for hereditary colorectal cancer syndromes was 1.3% and for hereditary breast and ovarian cancer syndrome was 1.6%. BRCA1 and BRCA2 mutations were the most prevalent with the positive rate of 1.3% in the general cohort and 5.1% in breast or ovarian cancer patients. Most of BRCA1 mutations located at the BRCA C-terminus domains and the top recurrent mutation was NM_007294.3:c.5251C>T (p.Arg1751Ter). One novel variant NM_000038.6(APC):c.6665C>A (p.Pro2222His) was found in a breast cancer patient with a strong family history of cancer. A case study of hereditary cancer syndrome was illustrated to highlight the importance of genetic testing.ConclusionThis is the first largest analysis of carrier frequency and mutation spectrum of HCS in Vietnam. The findings demonstrate the clinical significance of multigene panel testing to identify carriers and their at-risk relatives for better cancer surveillance and management strategies.

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Secondary Prevention in Hereditary Breast and/or Ovarian Cancer Syndromes Other Than BRCA

Journal of Oncology ◽

10.1155/2020/6384190 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10 ◽

Cited By ~ 1

Author(s):

Claudia Piombino ◽

Laura Cortesi ◽

Matteo Lambertini ◽

Kevin Punie ◽

Giovanni Grandi ◽

...

Keyword(s):

Ovarian Cancer ◽

Secondary Prevention ◽

Hereditary Cancer ◽

Precancerous Lesions ◽

Diffuse Gastric Cancer ◽

Repair System ◽

Hereditary Cancer Syndromes ◽

Cancer Syndrome ◽

Brca1 And Brca2 ◽

Cancer Syndromes

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.

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Ovarian cancer as part of hereditary cancer syndromes (review)

RESEARCH RESULTS IN BIOMEDICINE ◽

10.18413/2658-6533-2021-7-4-0-2 ◽

2021 ◽

Vol 7 (4) ◽

Keyword(s):

Ovarian Cancer ◽

Hereditary Cancer ◽

Hereditary Cancer Syndromes ◽

Cancer Syndromes

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Adult cancer survivorship referrals for hereditary cancer genetic testing.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.7_suppl.183 ◽

2018 ◽

Vol 36 (7_suppl) ◽

pp. 183-183

Author(s):

Farzana L. Walcott ◽

Rebecca Davidson Kaltman ◽

Elizabeth Hatcher ◽

Cam Ha ◽

Tara Biagi ◽

...

Keyword(s):

Genetic Testing ◽

Family History ◽

High Risk ◽

Cancer Survivorship ◽

Nurse Practitioner ◽

Hereditary Cancer ◽

Hereditary Cancer Syndromes ◽

History Of ◽

Cancer Syndromes ◽

History Of Cancer

183 Background: Genetic testing for hereditary cancer syndromes is underutilized among cancer patients. Cancer survivorship clinics may identify individuals at risk for hereditary cancer. We present the number of referrals from George Washington (GW) Adult Cancer Survivorship Clinic (ACS) to the GW Ruth Paul Hereditary Cancer Program (RPHCP) to demonstrate the feasibility of identifying high risk individuals in cancer survivorship. Methods: We reviewed the number of patients seen at the GW ACS and subsequent referrals to the GW RPHCP for genetic counseling/testing. An IRB approved research registry was used for retrieval of the data. The ACS clinic is staffed by a physician internist trained in clinical cancer genetics and a nurse practitioner trained in cancer survivorship. Results: 261 patients were seen in ACS from January 1, 2016, to September 30, 2017. Twenty patients (7.6%) were referred to RPHCP based on personal/family cancer history. Three patients were not consented for the research registry, leaving a total of 17 patients for this analysis. Fifteen (88.2%) patients were referred by the physician and 2/17 (11.7%) were referred by the nurse practitioner. Sixteen patients had genetic testing (94.1%) and results were: 5/16 (31.2%) positive, 6/16 (37.5%) negative, and 3/16 (18.7%) had a variant of unknown significance (VUS). Results on 2 patients are pending. One patient deferred testing. Of the 17 patients referred, 14/17 (82.3%) had personal/family history of cancer and had seen an oncologist. Cancer sites and germline mutations identified were: bilateral breast cancer and bladder cancer (BRCA2), prostate cancer (MUTYH), breast and ovarian cancer (BRCA1), endometrial cancer (APC). One patient without cancer was referred by an oncologist for a previously identified familial MLH1 mutation, and was positive. Conclusions: Cancer survivorship clinics may identify individuals appropriate for genetic testing for hereditary cancer syndromes. This is likely an underestimate as not all cancer patients are seen in survivorship clinic. Systematic capture of personal and family history of cancer in cancer survivors may enhance utilization of genetic testing services among cancer survivors and identification of high risk individuals.

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Validation of a Digital Identification Tool for Individuals at Risk for Hereditary Cancer Syndromes

10.20944/preprints201807.0476.v1 ◽

2018 ◽

Author(s):

Leslie Bucheit ◽

Katherine Johansen Taber ◽

Kaylene Ready

Keyword(s):

At Risk ◽

High Risk ◽

Lynch Syndrome ◽

Hereditary Cancer ◽

Hereditary Cancer Syndromes ◽

Independent Events ◽

Digital Identification ◽

Cancer Syndromes ◽

Testing Criteria ◽

Identification Tool

The number of individuals meeting criteria for genetic counseling and testing for hereditary cancer syndromes (HCS) is far less than the number that actually receive it. To facilitate identification of patients at risk for HCS, Counsyl developed a digital identification tool (digital ID tool) to match personal and family cancer history to National Comprehensive Cancer Network (NCCN) BRCA-related Hereditary Breast and Ovarian Cancer (HBOC), Lynch syndrome, and polyposis testing criteria in one-to-one, automated fashion. The purpose of this study was to validate the ability of the digital ID tool to accurately identify histories that do and do not meet NCCN testing criteria. Methods: Third-party recorded three-generation pedigrees were retrospectively reviewed by a certified genetic counselor (CGC) to determine if independent events included in pedigree histories met NCCN guidelines, and were then sorted into groups: high risk events (meets criteria) and low risk events (does not meet criteria). Events were entered into the digital ID tool to determine the extent of its concordance with events sorted by CGC review. Statistical tests of accuracy were calculated at a 95% confidence interval (CI). Results: 197 pedigrees were reviewed consecutively representing 765 independent events for analysis across groups. 382/382 (100%) high risk events identified by the digital ID tool and 381/383 (99.47%) low risk events identified by the digital ID tool were concordant with CGC sorting. The digital ID tool had a sensitivity of 100% (99.04-100% CI) and specificity of 99.48% (98.13-99.94% CI). The overall accuracy of the digital ID tool was estimated to be 99.74% (99.06-99.97% CI), reflecting the rate at which the digital ID tool reached the same conclusion as that of CGC review of pedigree events for the recommendation of genetic testing for individuals at risk for HCS. Conclusions: The digital ID tool accurately matches NCCN criteria in one-to-one fashion to identify at-risk individuals for HCS and may be useful in clinical practice, specifically for BRCA-related HBOC and Lynch Syndrome.

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