Population-based genetic testing of asymptomatic women for breast and ovarian cancer susceptibility

Rowley, Simone M.; Mascarenhas, Lyon; Devereux, Lisa; Li, Na; Amarasinghe, Kaushalya; Zethoven, Magnus; Lee, Jue Er Amanda; Lewis, Alexandra; Morgan, James; Limb, Sharne; Young, Mary‐Anne; James, Paul; Trainer, Alison H.; Campbell, Ian G.

doi:10.1038/s41436-018-0277-0

Cited by 50 publications

(68 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While ethnicity differences between the cases and GnomAD exist, these were demonstrated by PCA to be minimal with their predominant (over 95%) Western European ancestry being well matched with the GnomAD NFE non-cancer cohort. In addition, the frequencies of LoF mutations in HBOC genes in GnomAD were broadly comparable to our local population control figures from prior studies 43,44 , giving us confidence that in the context of a gene discovery phase, GnomAD is a suitable surrogate control population.…”

Section: None Of the Genes Identified By Dicks Et Al (Including Fancm)supporting

confidence: 80%

Exome sequencing of familial high-grade serous ovarian carcinoma reveals heterogeneity for rare candidate susceptibility genes

et al. 2020

Self Cite

View full text Add to dashboard Cite

High-grade serous ovarian carcinoma (HGSOC) has a significant hereditary component, approximately half of which cannot be explained by known genes. To discover genes, we analyse germline exome sequencing data from 516 BRCA1/2-negative women with HGSOC, focusing on genes enriched with rare, protein-coding loss-of-function (LoF) variants. Overall, there is a significant enrichment of rare protein-coding LoF variants in the cases (p < 0.0001, chi-squared test). Only thirty-four (6.6%) have a pathogenic variant in a known or proposed predisposition gene. Few genes have LoF mutations in more than four individuals and the majority are detected in one individual only. Forty-three highly-ranked genes are identified with three or more LoF variants that are enriched by threefold or more compared to Gno-mAD. These genes represent diverse functional pathways with relatively few involved in DNA repair, suggesting that much of the remaining heritability is explained by previously underexplored genes and pathways.

show abstract

Section: None Of the Genes Identified By Dicks Et Al (Including Fancm)supporting

confidence: 80%

Exome sequencing of familial high-grade serous ovarian carcinoma reveals heterogeneity for rare candidate susceptibility genes

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…Some studies have offered return of incidental or secondary findings of post hoc genetic testing undertaken in patients recruited for other research purposes. Thompson et al undertook post-hoc genetic testing for BRCA mutations in 1997 women and Rowley et al reported testing in 5908 women over 40 years (mean age 59.2 years) undergoing mammographic screening for BC in the Australian Life-pool study [ 70 , 71 ]. Secondary findings of BRCA testing in 50,726 men and women have also been reported through the MyCode Community Health Initiative [ 72 , 73 ].…”

Section: Resultsmentioning

confidence: 99%

Population Based Testing for Primary Prevention: A Systematic Review

Manchanda

Gaba

2018

Cancers

View full text Add to dashboard Cite

The current clinical model for genetic testing is based on clinical-criteria/family-history (FH) and a pre-defined mutation probability threshold. It requires people to develop cancer before identifying unaffected individuals in the family to target prevention. This process is inefficient, resource intensive and misses >50% of individuals or mutation carriers at risk. Population genetic-testing can overcome these limitations. It is technically feasible to test populations on a large scale; genetic-testing costs are falling and acceptability and awareness are rising. MEDLINE, EMBASE, Pubmed, CINAHL and PsychINFO databases were searched using free-text and MeSH terms; retrieved reference lists of publications were screened; additionally, web-based platforms, Google, and clinical-trial registries were searched. Quality of studies was evaluated using appropriate check-lists. A number of studies have evaluated population-based BRCA-testing in the Jewish population. This has been found to be acceptable, feasible, clinically-effective, safe, associated with high satisfaction rates and extremely cost-effective. Data support change in guidelines for population-based BRCA-testing in the Jewish population. Population panel testing for BRCA1/BRCA2/RAD51C/RAD51D/BRIP1/PALB2 gene mutations is the most cost-effective genetic-testing strategy in general-population women and can prevent thousands more breast and ovarian cancers than current clinical-criteria based approaches. A few ongoing studies are evaluating population-based genetic-testing for multiple cancer susceptibility genes in the general population but more implementation studies are needed. A future population-testing programme could also target other chronic diseases.

show abstract

“…Recently, several studies have demonstrated that the prevalence of germline PVs and gene-specific risk estimates could change, not only based on family history and type/molecular subtype of the tumors but also on the basis of race, ethnicity and different geographic location [28][29][30].…”

Section: Introductionmentioning

confidence: 99%

Hereditary Breast and Ovarian Cancer in Families from Southern Italy (Sicily)—Prevalence and Geographic Distribution of Pathogenic Variants in BRCA1/2 Genes

Incorvaia

Fanale

Badalamenti

et al. 2020

Cancers

View full text Add to dashboard Cite

Recent advances in the detection of germline pathogenic variants (PVs) in BRCA1/2 genes have allowed a deeper understanding of the BRCA-related cancer risk. Several studies showed a significant heterogeneity in the prevalence of PVs across different populations. Because little is known about this in the Sicilian population, our study was aimed at investigating the prevalence and geographic distribution of inherited BRCA1/2 PVs in families from this specific geographical area of Southern Italy. We retrospectively collected and analyzed all clinical information of 1346 hereditary breast and/or ovarian cancer patients genetically tested for germline BRCA1/2 PVs at University Hospital Policlinico “P. Giaccone” of Palermo from January 1999 to October 2019. Thirty PVs were more frequently observed in the Sicilian population but only some of these showed a specific territorial prevalence, unlike other Italian and European regions. This difference could be attributed to the genetic heterogeneity of the Sicilian people and its historical background. Therefore hereditary breast and ovarian cancers could be predominantly due to BRCA1/2 PVs different from those usually detected in other geographical areas of Italy and Europe. Our investigation led us to hypothesize that a higher prevalence of some germline BRCA PVs in Sicily could be a population-specific genetic feature of BRCA-positive carriers.

show abstract

Population-based genetic testing of asymptomatic women for breast and ovarian cancer susceptibility

Cited by 50 publications

References 37 publications

Exome sequencing of familial high-grade serous ovarian carcinoma reveals heterogeneity for rare candidate susceptibility genes

Exome sequencing of familial high-grade serous ovarian carcinoma reveals heterogeneity for rare candidate susceptibility genes

Population Based Testing for Primary Prevention: A Systematic Review

Hereditary Breast and Ovarian Cancer in Families from Southern Italy (Sicily)—Prevalence and Geographic Distribution of Pathogenic Variants in BRCA1/2 Genes

Contact Info

Product

Resources

About