Population screening for BRCA1/BRCA2 founder mutations in Ashkenazi Jews: proactive recruitment compared with self-referral

Lieberman, Sari; Tomer, Ariela; Ben-Chetrit, Avi; Olsha, Oded; Strano, Shalom; Beeri, Rachel; Koka, Sivan; Fridman, Hila; Djemal, Karen; Glick, Itzhak; Zalut, Todd; Segev, Shlomo; Sklair, Miri; Kaufman, Bella; Lahad, Amnon; Raz, Aviad E.; Levy-Lahad, Ephrat

doi:10.1038/gim.2016.182

Cited by 54 publications

(90 citation statements)

References 41 publications

(52 reference statements)

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“…Our findings of BRCA testing acceptability are consistent with reports from Israel and Canada . Our uptake was slightly higher than the 67% reported in the Israeli study .…”

Section: Discussionsupporting

confidence: 91%

“…The Israeli/Canadian studies provided only post‐test counselling to mutation carriers or those with a strong family history (FH) of cancer. High satisfaction rates have been reported in all three studies . A population‐based approach identifies >50% additional BRCA ‐carriers compared with clinical criteria/FH‐based testing, does not detrimentally affect psychological well‐being or quality‐of‐life on a population basis, and has been found to be extremely cost‐effective .…”

Section: Introductionmentioning

confidence: 78%

“…High satisfaction rates have been reported in all three studies. 1,[4][5][6] A populationbased approach identifies >50% additional BRCA-carriers compared with clinical criteria/FH-based testing, does not detrimentally affect psychological well-being or quality-oflife on a population basis, 1,5 and has been found to be extremely cost-effective. 7 This has led to calls by a number of experts for changing the paradigm to population-based BRCA testing in the AJ population.…”

Section: Introductionmentioning

confidence: 99%

“…8,9 Only limited data exist on attitude and factors affecting uptake of population-based BRCA testing in the Jewish population, and these are largely restricted to women. 5,10 Differences have also been reported between those who are selfreferred and those recruited through clinical services. 5 The Jewish population is the first population for whom population-based BRCA testing is likely to become a reality.…”

Section: Introductionmentioning

confidence: 99%

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Attitude towards and factors affecting uptake of population‐based BRCA testing in the Ashkenazi Jewish population: a cohort study

Manchanda

Burnell

Gaba

et al. 2019

BJOG

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Objective To evaluate factors affecting unselected population‐based BRCA testing in Ashkenazi Jews (AJ). Design Cohort‐study set within recruitment to the GCaPPS trial (ISRCTN73338115). Setting North London AJ population. Population or sample Ashkenazi Jews women/men >18 years, recruited through self‐referral. Methods Ashkenazi Jews women/men underwent pre‐test counselling for BRCA testing through recruitment clinics (clusters). Consenting individuals provided blood samples for BRCA testing. Data were collected on socio‐demographic/family history/knowledge/psychological well‐being along with benefits/risks/cultural influences (18‐item questionnaire measuring ‘attitude’). Four‐item Likert‐scales analysed initial ‘interest’ and ‘intention‐to‐test’ pre‐counselling. Uni‐ and multivariable logistic regression models evaluated factors affecting uptake/interest/intention to undergo BRCA testing. Statistical inference was based on cluster robust standard errors and joint Wald tests for significance. Item‐Response Theory and graded‐response models modelled responses to 18‐item questionnaire. Main outcome measures Interest, intention, uptake, attitude towards BRCA testing. Results A total of 935 individuals (women = 67%/men = 33%; mean age = 53.8 (SD = 15.02) years) underwent pre‐test genetic‐counselling. During the pre‐counselling, 96% expressed interest in and 60% indicated a clear intention to undergo BRCA testing. Subsequently, 88% opted for BRCA testing. BRCA‐related knowledge (P = 0.013) and degree‐level education (P = 0.01) were positively and negatively (respectively) associated with intention‐to‐test. Being married/cohabiting had four‐fold higher odds for BRCA testing uptake (P = 0.009). Perceived benefits were associated with higher pre‐counselling odds for interest in and intention to undergo BRCA testing. Reduced uncertainty/reassurance were the most important factors contributing to decision‐making. Increased importance/concern towards risks/limitations (confidentiality/insurance/emotional impact/inability to prevent cancer/marriage ability/ethnic focus/stigmatisation) were significantly associated with lower odds of uptake of BRCA testing, and discriminated between acceptors and decliners. Male gender/degree‐level education (P = 0.001) had weaker correlations, whereas having children showed stronger (P = 0.005) associations with attitudes towards BRCA testing. Conclusions BRCA testing in the AJ population has high acceptability. Pre‐test counselling increases awareness of disadvantages/limitations of BRCA testing, influencing final cost‐benefit perception and decision‐making on undergoing testing. Tweetable abstract BRCA testing in Ashkenazi Jews has high acceptability and uptake. Pre‐test counselling facilitates informed decision‐making.

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“…Our findings of BRCA testing acceptability are consistent with reports from Israel and Canada . Our uptake was slightly higher than the 67% reported in the Israeli study .…”

Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 78%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Attitude towards and factors affecting uptake of population‐based BRCA testing in the Ashkenazi Jewish population: a cohort study

Manchanda

Burnell

Gaba

et al. 2019

BJOG

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“…6,7 In AJ women with a diagnosis of breast or ovarian cancer, the prevalence of a BRCA1/2 founder mutation is estimated to be as high as 10% and 41%, respectively. [11][12][13][14] Mutations other than BRCA1/2 founder mutations can be divided into 2 categories: 1) nonfounder mutations located within the BRCA1/2 genes; and 2) mutations in cancer-associated genes other than BRCA1/2. The National Comprehensive Cancer Network (NCCN) guidelines regarding BRCA-related breast and/or ovarian cancer syndrome continue to recommend that, for AJ patients, the first step in genetic assessment should be BRCA1/2 founder mutation testing.…”

Section: Introductionmentioning

confidence: 99%

Prevalence of nonfounder BRCA1/2 mutations in Ashkenazi Jewish patients presenting for genetic testing at a hereditary breast and ovarian cancer center

Frey

Kopparam

Zhou

et al. 2018

Cancer

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BACKGROUND: Genetic assessment in Ashkenazi Jewish (AJ) patients often is limited to BRCA1/2 founder mutation testing. With access to time-efficient and cost-efficient multigene panel testing, some advocate expanding genetic testing in this population. However, to the best of the authors' knowledge, rates of nonfounder BRCA1/2 mutations and mutations in cancer-associated genes other than BRCA1/2 among AJ are not known. In the current study, the authors sought to assess the prevalence of mutations other than BRCA1/2 founder mutations among AJ patients undergoing genetic assessment. METHODS: The authors reviewed the medical records for all AJ patients who underwent genetic assessment at a single institution between June 2013 and December 2016. Mutations were categorized as 1) BRCA1/2 AJ founder mutations (BRCA1 185delAG, BRCA1 5382insC, or BRCA2 6174delT); 2) nonfounder BRCA1/2 mutations; or 3) mutations in non-BRCA1/2 cancer-associated genes. RESULTS: A total of 732 AJ patients underwent genetic assessment. Of these, 371 patients (51%) had a personal history of breast or ovarian cancer, 540 patients (73.8%) had a family history of breast cancer, and 132 patients (18%) had a family history of ovarian cancer. In the study population, 101 patients (13.8%) were found to have a pathogenic mutation, 78 patients (10.7%) had a BRCA1/2 founder mutation, 3 patients (0.4%) had a nonfounder BRCA1/2 mutation, and 20 patients (2.7%) had a mutation in a non-BRCA1/2 cancer-associated gene. Non-BRCA1/2 cancer-associated genes harboring mutations included RAD51D, TP53, mutS homolog 6 (MSH6), checkpoint kinase 2 (CHEK2), adenomatous polyposis coli (APC), and Fanconi anemia group C protein (FANCC). CONCLUSIONS: Among AJ patients found to have a pathogenic mutation on genetic assessment, approximately 22.8% had a mutation that would be missed with BRCA1/2 AJ founder mutation testing. Comprehensive multigene panel sequencing can provide clinically relevant genetic information for AJ patients and should be considered for genetic assessment in this population. Cancer 2019;125:690-697.

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Risk Assessment, Genetic Counseling, and Genetic Testing forBRCA-Related Cancer

Owens

Davidson

Krist

et al. 2019

JAMA

302

116

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US Preventive Services Task Force IMPORTANCE Potentially harmful mutations of the breast cancer susceptibility 1 and 2 genes (BRCA1/2) are associated with increased risk for breast, ovarian, fallopian tube, and peritoneal cancer. For women in the United States, breast cancer is the most common cancer after nonmelanoma skin cancer and the second leading cause of cancer death. In the general population, BRCA1/2 mutations occur in an estimated 1 in 300 to 500 women and account for 5% to 10% of breast cancer cases and 15% of ovarian cancer cases. OBJECTIVE To update the 2013 US Preventive Services Task Force (USPSTF) recommendation on risk assessment, genetic counseling, and genetic testing for BRCA-related cancer. EVIDENCE REVIEW The USPSTF reviewed the evidence on risk assessment, genetic counseling, and genetic testing for potentially harmful BRCA1/2 mutations in asymptomatic women who have never been diagnosed with BRCA-related cancer, as well as those with a previous diagnosis of breast, ovarian, tubal, or peritoneal cancer who have completed treatment and are considered cancer free. In addition, the USPSTF reviewed interventions to reduce the risk for breast, ovarian, tubal, or peritoneal cancer in women with potentially harmful BRCA1/2 mutations, including intensive cancer screening, medications, and risk-reducing surgery. FINDINGS For women whose family or personal history is associated with an increased risk for harmful mutations in the BRCA1/2 genes, or who have an ancestry associated with BRCA1/2 gene mutations, there is adequate evidence that the benefits of risk assessment, genetic counseling, genetic testing, and interventions are moderate. For women whose personal or family history or ancestry is not associated with an increased risk for harmful mutations in the BRCA1/2 genes, there is adequate evidence that the benefits of risk assessment, genetic counseling, genetic testing, and interventions are small to none. Regardless of family or personal history, the USPSTF found adequate evidence that the overall harms of risk assessment, genetic counseling, genetic testing, and interventions are small to moderate. CONCLUSIONS AND RECOMMENDATION The USPSTF recommends that primary care clinicians assess women with a personal or family history of breast, ovarian, tubal, or peritoneal cancer or who have an ancestry associated with BRCA1/2 gene mutations with an appropriate brief familial risk assessment tool. Women with a positive result on the risk assessment tool should receive genetic counseling and, if indicated after counseling, genetic testing. (B recommendation) The USPSTF recommends against routine risk assessment, genetic counseling, or genetic testing for women whose personal or family history or ancestry is not associated with potentially harmful BRCA1/2 gene mutations. (D recommendation)

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Population screening for BRCA1/BRCA2 founder mutations in Ashkenazi Jews: proactive recruitment compared with self-referral

Cited by 54 publications

References 41 publications

Attitude towards and factors affecting uptake of population‐based BRCA testing in the Ashkenazi Jewish population: a cohort study

Attitude towards and factors affecting uptake of population‐based BRCA testing in the Ashkenazi Jewish population: a cohort study

Prevalence of nonfounder BRCA1/2 mutations in Ashkenazi Jewish patients presenting for genetic testing at a hereditary breast and ovarian cancer center

Risk Assessment, Genetic Counseling, and Genetic Testing forBRCA-Related Cancer

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