FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4221043056> ?p ?o ?g. }

• W4221043056 endingPage "S194" @default.
• W4221043056 startingPage "S193" @default.
• W4221043056 abstract "The logistical, financial, and social barriers to cascade genetic testing uptake have been well studied; however, the impact of proband indication for testing on uptake of cascade testing remains unknown. The aim of this study was to determine if cascade genetic testing uptake rates were significantly different between relatives of probands undergoing testing due to a relevant family or personal history (diagnostic testing) and relatives of probands undergoing non-indication based (proactive screening). We hypothesized that probands undergoing diagnostic testing would generate more cascade testing uptake than probands pursuing proactive screening. Two retrospective cohorts were compiled with patients that underwent germline genetic testing or proactive screening at Invitae from January 2017 to April 2021. The diagnostic proband cohort included individuals who had indication-based testing via one of the following panels: the Invitae Common Hereditary Cancers Panel (up to 47 genes) or the Invitae Familial Hypercholesterolemia Panel (up to 4 genes). The proactive proband cohort included individuals who had screening via one of the following panels: the Invitae Cancer Screen (up to 61 genes), the Invitae Cardio Screen (up to 77 genes), or the Invitae Genetic Health Screen (up to 147 genes). Forty-nine genes were analyzed in both proactive and diagnostic cohorts, while 101 genes were unique to proactive, and two genes were unique to diagnostic. Probands in the diagnostic cohort were unselected for test indication (ie, affected versus family history), sex, self-reported ancestry, or age. Probands in the proactive cohort were unselected for sex, self-reported ancestry, or age. Relatives of probands harboring a reportable variant (ie, pathogenic/likely pathogenic [P/LP], increased risk allele, pathogenic - low penetrance), including carrier status only, were eligible for no-charge cascade testing for the identified variant(s) for up to 150 days following the proband’s test report date. The number of probands with positive findings (ie, 1 P/LP variant in autosomal dominant or 2 P/LP variants in autosomal recessive disorders) and carrier status only were calculated separately. Frequency of cascade testing uptake for both diagnostic and proactive cohorts was calculated based on type of result (medically actionable or carrier). Age (2-sample, 2-tailed t-test) and sex (difference in proportion for two independent samples) of probands with a reportable finding were compared based on the uptake of cascade testing in both cohorts. A total of 271,246 probands (254,811 diagnostic, 16,435 proactive) were included in this analysis. Most probands with diagnostic testing were female (n=220,993, 86.7%) and had cancer panels ordered (n=248,293, 97.4%), while a majority of probands with proactive screening were female (n=9,518, 57.9%) and had both cancer and cardiology panels ordered (n=10,326, 62.8%). In both cohorts, most probands self-reported White ancestry (diagnostic, n=164,415, 64.5%; proactive, n=9,976, 60.7%). Average age at testing among diagnostic probands was older compared to proactive probands (55.2±14.7 years and 48.3±13.2 years, respectively). A medically actionable result was identified in 10.0% (n=25,530) and 14.2% (n=2,333) of probands receiving diagnostic testing or proactive screening, respectively, of which 97.8% (n=24,962/25,530) and 44.4% (n=1,037/2,333) were in genes available for requisition in both cohorts. Carrier status was reported for 2.0% (n=5,041) and 21.3% (n=3,508) of diagnostic and proactive probands, respectively, of which 99.6% (n=5,021/5,041) and 8.4% (n=293/3,508) were in genes common to both panels. Among probands with a medically actionable result, 6,558 (25.7%) diagnostic probands had 14,572 (mean 2.2 relatives/proband) relatives pursue cascade testing while 131 (5.6%) proactive probands had 248 (mean 2 relatives/proband) relatives undergo cascade testing (p < 0.0001). The majority of cascade testing occurred when positive findings were in genes available on both panels (diagnostic, probands n=6,473, relatives n=14,410; proactive, probands n=100, relatives n=186). Uptake of cascade testing was highest when the proband was tested for hereditary cancer (Table 1). When a carrier result was returned, cascade testing was pursued in 561 relatives from 335 (6.6%) diagnostic probands and 43 relatives from 25 (0.7%) proactive probands. When considering only positive results in shared genes, relatives were more often female (diagnostic, n=9,754, 67.7%; proactive, n=125, 67.2%) and White (diagnostic, n=10,640, 73.8%; proactive, n=119, 64.0%). Average age at testing was 45.5±18.3 years and 44.5±21.0 years in diagnostic and proactive relatives, respectively. Cancer-related genes were the most commonly ordered testing among relatives in both cohorts (diagnostic n=13,747, 94.3%; proactive n=152, 88.9%). Diagnostic probands with relatives who pursued cascade testing were significantly older than probands without cascade testing (cascade 54.6±16.0 years, no cascade 53.4±16.4 years, p = 6.6×10-8). No difference in age was observed among proactive probands (cascade 48.8±14.2 years, no cascade 47.5±13.3 years, p = 0.36). There was no difference in sex of probands with or without relatives tested in either the diagnostic (cascade, n=5,282 females, 81.6%; no cascade, n=14,916 females, 80.7%, p = 0.597) or proactive (cascade, n=65 females, 65.7%; no cascade, n=493 females, 52.7%, p = 0.192) cohorts. Probands undergoing diagnostic genetic testing generated significantly more cascade testing uptake among their relatives than probands undergoing proactive screening. Differences in cascade uptake rates may be due to a difference in perceived urgency felt by relatives of probands pursuing testing as a result of relevant personal or family history of disease. Further research should be done to better understand the impact of proband testing indication on relative cascade testing uptake. To maximize uptake of cascade testing, different messaging for the medical importance and benefits of cascade testing for relatives of probands undergoing proactive screening may be warranted.Tabled 1Diagnostic cohortProactive cohortProband test resultPositiveCarrierPositiveCarrier(n=24,962)(n=5,021)(n=1,037)(n=293)Probands with ≥1 relative tested, n (%) [max] Overall6,473/24,962 (25.9)333/5,021 (6.6)100/1,037 (9.6)4/293 (1.4) Cardio335/1,648 (20.3)0/30/70/0 Cancer6,138/23,314 (26.3)333/5,018 (6.6)52/417 (12.5)3/109 (2.8) BothNANA48/613 (7.8)1/184 (0.5)Relatives tested per family unit, mean (SD) [max] Overall2.2 (1.9) [30]1.7 (1.3) [13]2.0 (1.4) [8]1.3 (0.5) [2] Cardio2.5 (2.5) [30]000 Cancer2.2 (1.9) [27]1.7 (1.3) [13]2.0 (1.5) [8]1.3 (0.6) [2] BothNANA2.0 (1.3) [6]1 (NA) [1]Shared genes included: APC, APOB, ATM, AXIN2, BARD1, BMPR1A, BRCA1, BRCA2, BRIP1, CDH1, CDK4, CDKN2A, CHEK2, DICER1, EPCAM, GREM1, HOXB13, KIT, LDLR, LDLRAP1, MEN1, MLH1, MSH2, MSH3, MSH6, MUTYH, NBN, NF1, NTHL1, PALB2, PCSK9, PDGFRA, PMS2, POLD1, POLE, PTEN, RAD51C, RAD51D, SDHA, SDHB, SDHC, SDHD, SMAD4, STK11, TP53, TSC1, TSC2, VHL Open table in a new tab" @default.
• W4221043056 created "2022-04-03" @default.
• W4221043056 creator A5012651735 @default.
• W4221043056 creator A5041875720 @default.
• W4221043056 creator A5068779675 @default.
• W4221043056 creator A5071432763 @default.
• W4221043056 date "2022-03-01" @default.
• W4221043056 modified "2023-10-18" @default.
• W4221043056 title "eP307: The impact of proband indication for genetic testing on the uptake of cascade testing among relatives" @default.
• W4221043056 doi "https://doi.org/10.1016/j.gim.2022.01.343" @default.
• W4221043056 hasPublicationYear "2022" @default.
• W4221043056 type Work @default.
• W4221043056 citedByCount "0" @default.
• W4221043056 crossrefType "journal-article" @default.
• W4221043056 hasAuthorship W4221043056A5012651735 @default.
• W4221043056 hasAuthorship W4221043056A5041875720 @default.
• W4221043056 hasAuthorship W4221043056A5068779675 @default.
• W4221043056 hasAuthorship W4221043056A5071432763 @default.
• W4221043056 hasBestOaLocation W42210430561 @default.
• W4221043056 hasConcept C104317684 @default.
• W4221043056 hasConcept C126322002 @default.
• W4221043056 hasConcept C188997412 @default.
• W4221043056 hasConcept C201903717 @default.
• W4221043056 hasConcept C2780673598 @default.
• W4221043056 hasConcept C2781179581 @default.
• W4221043056 hasConcept C501734568 @default.
• W4221043056 hasConcept C54355233 @default.
• W4221043056 hasConcept C71924100 @default.
• W4221043056 hasConcept C72563966 @default.
• W4221043056 hasConcept C80227256 @default.
• W4221043056 hasConcept C86803240 @default.
• W4221043056 hasConceptScore W4221043056C104317684 @default.
• W4221043056 hasConceptScore W4221043056C126322002 @default.
• W4221043056 hasConceptScore W4221043056C188997412 @default.
• W4221043056 hasConceptScore W4221043056C201903717 @default.
• W4221043056 hasConceptScore W4221043056C2780673598 @default.
• W4221043056 hasConceptScore W4221043056C2781179581 @default.
• W4221043056 hasConceptScore W4221043056C501734568 @default.
• W4221043056 hasConceptScore W4221043056C54355233 @default.
• W4221043056 hasConceptScore W4221043056C71924100 @default.
• W4221043056 hasConceptScore W4221043056C72563966 @default.
• W4221043056 hasConceptScore W4221043056C80227256 @default.
• W4221043056 hasConceptScore W4221043056C86803240 @default.
• W4221043056 hasIssue "3" @default.
• W4221043056 hasLocation W42210430561 @default.
• W4221043056 hasOpenAccess W4221043056 @default.
• W4221043056 hasPrimaryLocation W42210430561 @default.
• W4221043056 hasRelatedWork W2039742182 @default.
• W4221043056 hasRelatedWork W2050398010 @default.
• W4221043056 hasRelatedWork W2082710928 @default.
• W4221043056 hasRelatedWork W2149357640 @default.
• W4221043056 hasRelatedWork W2240259195 @default.
• W4221043056 hasRelatedWork W2424389887 @default.
• W4221043056 hasRelatedWork W2801760893 @default.
• W4221043056 hasRelatedWork W3048703526 @default.
• W4221043056 hasRelatedWork W3118975915 @default.
• W4221043056 hasRelatedWork W4206712612 @default.
• W4221043056 hasVolume "24" @default.
• W4221043056 isParatext "false" @default.
• W4221043056 isRetracted "false" @default.
• W4221043056 workType "article" @default.