Uptake of Family-Specific Mutation Genetic Testing Among Relatives of Patients with Ovarian Cancer with BRCA1 or BRCA2 Mutation

Jeong, Go Woon; Shin, Woong‐Chul; Lee, Dong Ock; Seo, Sang Soo; Kang, Sokbom; Park, Soo‐Jin; Lim, Myong Cheol

doi:10.4143/crt.2020.364

Cited by 9 publications

(4 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As a result, this cohort consists of small numbers in some patient categories and tumor combinations, especially among males. Undertesting or underutilization of germline genetic testing among adult males is well established, 31‐36 and this cohort reflects this testing bias. Next, these analyses were limited to 21 well‐established cancer predisposition genes, and it is possible that if we evaluated more genes, such as those associated with cancers common to males and females (eg, BAP1 , CDKN2A , FH , MITF , POT1 , SDHB , TERT , and VHL ), more pronounced differences in sex‐specific PV frequencies would be evident.…”

Section: Discussionmentioning

confidence: 97%

Prevalence and spectrum of pathogenic variants among patients with multiple primary cancers evaluated by clinical characteristics

Bychkovsky

Yussuf

et al. 2021

Cancer

View full text Add to dashboard Cite

Background Multiple primary cancers (MPCs) are a hallmark of cancer predisposition syndromes. Here the frequency of germline pathogenic variants (PVs) among patients with MPCs is reported. Methods Patients with MPCs who underwent multigene panel testing from March 2012 to December 2016 were studied. Eligible patients had an analysis of 21 genes: ATM, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, EPCAM, MLH1, MSH2, MSH6, MUTYH, NBN, NF1, PALB2, PMS2, PTEN, RAD51C, RAD51D, STK11, and TP53. The frequencies of PVs by sex, number of cancers, and age at diagnosis were compared with 2‐sided χ2 tests or Fisher exact tests when the number was <10. Results Among the 9714 patients analyzed, most were female (91.1%) and White (71.0%); the median age at testing was 63 years, and the median ages at first and second cancer diagnoses were 49 and 58 years, respectively. Overall, 1320 (13.6%) had PVs. The prevalence of PVs increased with the number of primary cancers (PCs): 13.1% with 2 PCs, 15.9% with 3 PCs, and 18.0% with ≥4 PCs (P = .00056). Differences in the prevalence of PVs by age at diagnosis were significant: 14.7% with 2 PCs at an age < 50 years, 15.8% with 1 PC at an age < 50 years, and 12.0% with all PCs at an age ≥ 50 years (P = 2.07E–05). PVs by the age at second cancer diagnosis were also significant: 14.7% at an age < 50 years, 13.9% at an age of 50 to 69 years, and 11.4% at an age ≥ 70 years (P for trend = .005). Conclusions Among patients with MPCs, there is a high frequency of germline PVs, with a higher frequency found among patients with a higher number of PCs. These findings suggest that genetic testing should be considered even among patients who are older at the diagnosis of an additional primary malignancy.

show abstract

Section: Discussionmentioning

confidence: 97%

Prevalence and spectrum of pathogenic variants among patients with multiple primary cancers evaluated by clinical characteristics

Bychkovsky

Yussuf

et al. 2021

Cancer

View full text Add to dashboard Cite

show abstract

“…Limitations of this study include a homogeneous (predominately White female participants) study population, most with a history of BC. Recognizing that men are less likely to un-dergo genetic testing, [54][55][56][57][58][59] there are ascertainment biases inherent in a cohort selected for genetic testing for cancer predisposition. Ordinarily, these ascertainment biases would lead to overestimations in the ORs for cancers.…”

Section: Limitationsmentioning

confidence: 99%

Differences in Cancer Phenotypes Among Frequent CHEK2 Variants and Implications for Clinical Care—Checking CHEK2

et al. 2022

View full text Add to dashboard Cite

ImportanceGermline CHEK2 pathogenic variants (PVs) are frequently detected by multigene cancer panel testing (MGPT), but our understanding of PVs beyond c.1100del has been limited.ObjectiveTo compare cancer phenotypes of frequent CHEK2 PVs individually and collectively by variant type.Design, Setting, and ParticipantsThis retrospective cohort study was carried out in a single diagnostic testing laboratory from 2012 to 2019. Overall, 3783 participants with CHEK2 PVs identified via MGPT were included. Medical histories of cancer in participants with frequent PVs, negative MGPT (wild type), loss-of-function (LOF), and missense were compared.Main Outcomes and MeasuresParticipants were stratified by CHEK2 PV type. Descriptive statistics were summarized including median (IQR) for continuous variables and proportions for categorical characteristics. Differences in age and proportions were assessed with Wilcoxon rank sum and Fisher exact tests, respectively. Frequencies, odds ratios (ORs), 95% confidence intervals were calculated, and P values were corrected for multiple comparisons where appropriate.ResultsOf the 3783 participants with CHEK2 PVs, 3473 (92%) were female and most reported White race. Breast cancer was less frequent in participants with p.I157T (OR, 0.66; 95% CI, 0.56-0.78; P<.001), p.S428F (OR, 0.59; 95% CI. 0.46-0.76; P<.001), and p.T476M (OR, 0.74; 95% CI, 0.56-0.98; P = .04) PVs compared with other PVs and an association with nonbreast cancers was not found. Following the exclusion of p.I157T, p.S428F, and p.T476M, participants with monoallelic CHEK2 PV had a younger age at first cancer diagnosis (P < .001) and were more likely to have breast (OR, 1.83; 95% CI, 1.66-2.02; P < .001), thyroid (OR, 1.63; 95% CI, 1.26-2.08; P < .001), and kidney cancer (OR, 2.57; 95% CI, 1.75-3.68; P < .001) than the wild-type cohort. Participants with a CHEK2 PV were less likely to have a diagnosis of colorectal cancer (OR, 0.62; 95% CI, 0.51-0.76; P < .001) compared with those in the wild-type cohort. There were no significant differences between frequent CHEK2 PVs and c.1100del and no differences between CHEK2 missense and LOF PVs.Conclusions and RelevanceCHEK2 PVs, with few exceptions (p.I157T, p.S428F, and p.T476M), were associated with similar cancer phenotypes irrespective of variant type. CHEK2 PVs were not associated with colorectal cancer, but were associated with breast, kidney, and thyroid cancers. Compared with other CHEK2 PVs, the frequent p.I157T, p.S428F, and p.T476M alleles have an attenuated association with breast cancer and were not associated with nonbreast cancers. These data may inform the genetic counseling and care of individuals with CHEK2 PVs.

show abstract

“…Random effects modelHeterogeneity: I 2 = 98%, W 2 = 1.1781, P = 0 Evans et al, 200966 Fehniger et al, 201315 Finlay et al, 200847 Fischer et al, 2012101 Griffin et al, 2020106 Hadley et al, 200362 Holloway et al, 200854 Jeong et al, 2021112 Julian-Reynier et al, 2000113 Lammens et al, 2010116 Levin et al, 201763 Li et al, 2017118 Lieberman et al, 2018119 McGivern et al, 2004120 Meijers-Heijboer et al, 200049 Menko et al, 202050 Petersen et al, 201843 Ponz de Leon et al, 2004124 Ramsoekh et al, 200753 Sanz et al, 201051 Seppälä et al, 201752 Sermijn et al, 201668 Suthers et al, 200617 Trottier et al, 201564 Wagner et al, 200255 Yoon et al, 201144 …”

mentioning

confidence: 99%

“…= 0.9682, P < .01 Barrow et al, 201545 Beard et al, 202089 Bednar et al, 202090 Blandy et al, 200358 Bodd et al, 200346 Brooks et al, 200459 Bruwer et al, 201393 Cody et al, 200860 Courtney et al, 201941 Gauna Cristaldo et al, 2019105 Dilzell et al, 201442 Evans et al, 200966 Finlay et al, 200847 Fischer et al, 2012101 Griffin et al, 2020106 Hadley et al, 200362 Holloway et al, 200854 Jeong et al, 2021112 Julian-Reynier et al, 2000113 Lammens et al, 2010116 Levin et al, 201763 Li et al, 2017118 Lieberman et al, 2018119 Meijers-Heijboer et al, 200049 Ponz de Leon et al, 2004124 Ramsoekh et al, 200753 Sanz et al, 201051 Seppälä et al, 201752 Trottier et al, 201564 Wagner et al, 200255 Yoon et al, 201144 …”

mentioning

confidence: 99%

Cascade Testing for Hereditary Cancer Syndromes: Should We Move Toward Direct Relative Contact? A Systematic Review and Meta-Analysis

Frey

Ahsan

Bergeron

et al. 2022

JCO

View full text Add to dashboard Cite

PURPOSE Evidence-based guidelines recommend cascade genetic counseling and testing for hereditary cancer syndromes, providing relatives the opportunity for early detection and prevention of cancer. The current standard is for patients to contact and encourage relatives (patient-mediated contact) to undergo counseling and testing. Direct relative contact by the medical team or testing laboratory has shown promise but is complicated by privacy laws and lack of infrastructure. We sought to compare outcomes associated with patient-mediated and direct relative contact for hereditary cancer cascade genetic counseling and testing in the first meta-analysis on this topic. MATERIALS AND METHODS We conducted a systematic review and meta-analysis in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO No.: CRD42020134276). We searched key electronic databases to identify studies evaluating hereditary cancer cascade testing. Eligible trials were subjected to meta-analysis. RESULTS Eighty-seven studies met inclusion criteria. Among relatives included in the meta-analysis, 48% (95% CI, 38 to 58) underwent cascade genetic counseling and 41% (95% CI, 34 to 48) cascade genetic testing. Compared with the patient-mediated approach, direct relative contact resulted in significantly higher uptake of genetic counseling for all relatives (63% [95% CI, 49 to 75] v 35% [95% CI, 24 to 48]) and genetic testing for first-degree relatives (62% [95% CI, 49 to 73] v 40% [95% CI, 32 to 48]). Methods of direct contact included telephone calls, letters, and e-mails; respective rates of genetic testing completion were 61% (95% CI, 51 to 70), 48% (95% CI, 37 to 59), and 48% (95% CI, 45 to 50). CONCLUSION Most relatives at risk for hereditary cancer do not undergo cascade genetic counseling and testing, forgoing potentially life-saving medical interventions. Compared with patient-mediated contact, direct relative contact increased rates of cascade genetic counseling and testing, arguing for a shift in the care delivery paradigm, to be confirmed by randomized controlled trials.

show abstract

Uptake of Family-Specific Mutation Genetic Testing Among Relatives of Patients with Ovarian Cancer with BRCA1 or BRCA2 Mutation

Cited by 9 publications

References 18 publications

Prevalence and spectrum of pathogenic variants among patients with multiple primary cancers evaluated by clinical characteristics

Prevalence and spectrum of pathogenic variants among patients with multiple primary cancers evaluated by clinical characteristics

Differences in Cancer Phenotypes Among Frequent CHEK2 Variants and Implications for Clinical Care—Checking CHEK2

Cascade Testing for Hereditary Cancer Syndromes: Should We Move Toward Direct Relative Contact? A Systematic Review and Meta-Analysis

Contact Info

Product

Resources

About