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1.
J Am Coll Surg ; 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31672679

RESUMO

BACKGROUND: Direct-to-consumer BRCA testing will increase BRCA diagnoses and subsequent abdominal imaging. It is unclear whether BRCA-carriers are at higher risk of developing pancreatic cysts (PCs) or cyst-associated pancreatic adenocarcinoma (PDAC). We investigate the prevalence of PCs in BRCA-tested patients, and whether BRCA-carriers have higher rates of PDAC when PCs are found. STUDY DESIGN: This is a retrospective cross-sectional study of patients with BRCA testing and abdominal imaging between 1996-2018. PCs were identified on original imaging reports. Prevalence and risk characteristics of PCs, as well as incidence of PDAC, were compared between BRCA+, BRCA-, and BRCA-untested patients. RESULTS: PCs were identified in 4045 patients among 128,164 unique patients with abdominal imaging, including 33 patients with PCs in 1,113 BRCA-tested patients. There was no difference in PC prevalence between BRCA+, BRCA- and untested patients (3.6%, 2.6%, 3.2% respectively; p= 0.64). PCs were diagnosed in BRCA+ patients at a younger age (57.1 vs 65.3 years, p<0.001), however there was no difference in risk stratification compared to BRCA- or untested patients by consensus criteria. Across the population of imaged patients, patients with PCs had significantly higher rates of PDAC compared to those without PCs (18.2% vs 2.4%, p<0.001). Incidence of cyst-associated PDAC was similar in BRCA+ and BRCA- patients (13.3% vs 22.2%, p= 0.84). CONCLUSION: BRCA+ patients have similar rates of PCs, high-risk features in their cysts, and PDAC as BRCA- and untested patients. BRCA+ patients likely do not require dedicated abdominal imaging to evaluate for PCs and should follow similar management guidelines as the untested general population if an incidental PC is identified.

2.
Cancer ; 125(16): 2829-2836, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31206626

RESUMO

BACKGROUND: Breast cancer (BC) is the most common cancer and related cause of mortality among Hispanics, yet susceptibility has been understudied. BRCA1 and BRCA2 (BRCA) mutations explain less than one-half of hereditary BC, and the proportion associated with other BC susceptibility genes is unknown. METHODS: Germline DNA from 1054 BRCA-mutation-negative Hispanic women with hereditary BC (BC diagnosed at age <51 years, bilateral BC, breast and ovarian cancer, or BC diagnosed at ages 51-70 years with ≥2 first-degree or second-degree relatives who had BC diagnosed at age <70 years), 312 local controls, and 887 multiethnic cohort controls was sequenced and analyzed for 12 known and suspected, high-penetrance and moderate-penetrance cancer susceptibility genes (ataxia telangiectasia mutated [ATM], breast cancer 1 interacting protein C-terminal helicase 1 [BRIP1], cadherin 1 [CDH1], checkpoint kinase 2 [CHEK2], nibrin [NBN], neurofibromatosis type 1 [NF1], partner and localizer of BRCA2 [PALB2], phosphatase and tensin homolog [PTEN], RAD51 paralog 3 [RAD51C], RAD51D, serine/threonine kinase 11 [STK11], and TP53). RESULTS: Forty-nine (4.6%) pathogenic or likely pathogenic variants (PVs) in 47 of 1054 participants (4.5%), including 21 truncating frameshift, 20 missense, 5 nonsense, and 4 splice variants, were identified in CHEK2 (n = 20), PALB2 (n = 18), ATM (n = 5), TP53 (n = 3), BRIP1 (n = 2), and CDH1 and NF1 (both n = 1) and none were identified in NBN, PTEN, STK11, RAD51C, or RAD51D. Nine participants carried the PALB2 c.2167_2168del PV (0.85%), and 14 carried the CHEK2 c.707T>C PV (1.32%). CONCLUSIONS: Of 1054 BRCA-negative, high-risk Hispanic women, 4.5% carried a PV in a cancer susceptibility gene, increasing understanding of hereditary BC in this population. Recurrent PVs in PALB2 and CHEK2 represented 47% (23 of 49) of the total, suggesting a founder effect. Accurate classification of variants was enabled by carefully controlling for ancestry and the increased identification of at-risk Hispanics for screening and prevention.

3.
Hum Mutat ; 40(10): 1781-1796, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31112363

RESUMO

BRCA1 and BRCA2 (BRCA1/2) pathogenic sequence variants (PSVs) confer elevated risks of multiple cancers. However, most BRCA1/2 PSVs reports focus on European ancestry individuals. Knowledge of the PSV distribution in African descent individuals is poorly understood. We undertook a systematic review of the published literature and publicly available databases reporting BRCA1/2 PSVs also accessed the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) database to identify African or African descent individuals. Using these data, we inferred which of the BRCA PSVs were likely to be of African continental origin. Of the 43,817 BRCA1/2 PSV carriers in the CIMBA database, 469 (1%) were of African descent. Additional African descent individuals were identified in public databases (n = 291) and the literature (n = 601). We identified 164 unique BRCA1 and 173 unique BRCA2 PSVs in individuals of African ancestry. Of these, 83 BRCA1 and 91 BRCA2 PSVs are of likely or possible African origin. We observed numerous differences in the distribution of PSV type and function in African origin versus non-African origin PSVs. Research in populations of African ancestry with BRCA1/2 PSVs is needed to provide the information needed for clinical management and decision-making in African descent individuals worldwide.

5.
J Natl Compr Canc Netw ; 16(8): 939-949, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30099370

RESUMO

The NCCN Guidelines for Colorectal Cancer (CRC) Screening outline various screening modalities as well as recommended screening strategies for individuals at average or increased-risk of developing sporadic CRC. The NCCN panel meets at least annually to review comments from reviewers within their institutions, examine relevant data, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize 2018 updates to the NCCN Guidelines, with a primary focus on modalities used to screen individuals at average-risk for CRC.

6.
Gynecol Oncol ; 149(1): 84-88, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29605055

RESUMO

OBJECTIVE: We sought to characterize referral patterns for genetic counseling for women with ovarian cancer and hypothesized that differences in referral and testing rates are shaped by socioeconomic factors. METHODS: Patients were identified by pathology reports from August 2012 to January 2016 containing the words "serous" or "ovarian." Patient information was obtained via electronic medical record. Primary outcomes were placement of a genetics referral and completion of counseling. A secondary outcome was completion of genetic testing. RESULTS: We identified 246 women with a diagnosis of ovarian cancer. Ten were previously counseled and excluded. 53% of patients were referred for counseling with mean time from diagnosis to counseling of 4.6months. Age and family history were not associated with referral, however rates differed by race with 61% of Caucasian and 40%, 38% and 33% of Asian, Latina and Black women, respectively, referred (p=0.035). Overall, 36% of patients diagnosed underwent counseling, and 33% were tested. English language (p<0.0001), high-grade serous histology (p=<0.0001) and private or Medicare insurance (p<0.0001) were significantly associated with referral. CONCLUSION: We have not yet reached the Society of Gynecologic Oncology recommendation for referral to genetics. Women of color and those with public insurance have lower referral rates. This disparity in care impacts cancer treatment options and prevents appropriate screening for other hereditary malignancies. To provide comprehensive oncology care, including genetic assessment, we recommend focusing on these barriers including improving outreach and interpreter services.


Assuntos
Testes Genéticos/estatística & dados numéricos , Neoplasias Ovarianas/etnologia , Neoplasias Ovarianas/genética , Grupo com Ancestrais do Continente Africano/genética , Grupo com Ancestrais do Continente Africano/estatística & dados numéricos , Grupo com Ancestrais do Continente Asiático/genética , Grupo com Ancestrais do Continente Asiático/estatística & dados numéricos , Grupo com Ancestrais do Continente Europeu/genética , Grupo com Ancestrais do Continente Europeu/estatística & dados numéricos , Feminino , Testes Genéticos/normas , Disparidades em Assistência à Saúde , Hispano-Americanos/genética , Hispano-Americanos/estatística & dados numéricos , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/economia , Encaminhamento e Consulta/estatística & dados numéricos , Estudos Retrospectivos , Programa de SEER , Estados Unidos/epidemiologia
7.
Hum Mutat ; 39(5): 593-620, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29446198

RESUMO

The prevalence and spectrum of germline mutations in BRCA1 and BRCA2 have been reported in single populations, with the majority of reports focused on White in Europe and North America. The Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) has assembled data on 18,435 families with BRCA1 mutations and 11,351 families with BRCA2 mutations ascertained from 69 centers in 49 countries on six continents. This study comprehensively describes the characteristics of the 1,650 unique BRCA1 and 1,731 unique BRCA2 deleterious (disease-associated) mutations identified in the CIMBA database. We observed substantial variation in mutation type and frequency by geographical region and race/ethnicity. In addition to known founder mutations, mutations of relatively high frequency were identified in specific racial/ethnic or geographic groups that may reflect founder mutations and which could be used in targeted (panel) first pass genotyping for specific populations. Knowledge of the population-specific mutational spectrum in BRCA1 and BRCA2 could inform efficient strategies for genetic testing and may justify a more broad-based oncogenetic testing in some populations.

8.
J Clin Oncol ; 27(24): 3981-6, 2009 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-19620492

RESUMO

PURPOSE: Lynch syndrome is associated with inherited germline mutations in mismatch repair (MMR) genes. Genetic testing in high-risk individuals may yield indeterminate results if no mutation is found or if a mutation of unclear pathogenic significance is observed. There are limited data regarding how well patients with Lynch syndrome understand the clinical implications of genetic test results. This study examines colorectal cancer (CRC) risk perception in individuals tested for MMR mutations and identifies the factors associated with an appropriate interpretation of their cancer risk. PATIENTS AND METHODS: A total of 159 individuals who met the Revised Bethesda Guidelines and had previously undergone genetic testing completed a questionnaire eliciting demographic data, cancer history, genetic test results, and an estimate of their CRC risk. Associations between clinical factors, genetic test results, and CRC risk perception were explored using multivariable analyses. RESULTS: Of the 100 individuals with a pathogenic mutation (true positive), 90 (90%) correctly estimated their CRC risk as "high" or "very high" compared with other individuals their age. However, only 23 (62%) of 37 individuals with an indeterminate genetic test result correctly estimated their risk. Individuals with a history of Lynch syndrome-associated cancer (odds ratio [OR], 0.1; 95% CI, 0.1 to 0.6) or indeterminate genetic test results (OR, 0.2; 95% CI, 0.1 to 0.6) were significantly less likely to estimate their CRC risk as increased. CONCLUSION: Patients at risk for Lynch syndrome with an indeterminate genetic test result may be falsely reassured. It is important that health care providers continue to discuss the implications of uninformative results on lifetime cancer risk.


Assuntos
Neoplasias Colorretais Hereditárias sem Polipose/genética , Neoplasias Colorretais/etiologia , Adolescente , Adulto , Idoso , Estudos Transversais , Reparo de Erro de Pareamento de DNA , Feminino , Aconselhamento Genético , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
9.
Psychooncology ; 17(8): 783-9, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18688785

RESUMO

OBJECTIVE: Li-Fraumeni syndrome (LFS) confers an increased risk of multiple types of cancer in both children and adults. Clinical genetic testing for deleterious germline p53 gene mutations can identify most LFS-affected families. We evaluated factors associated with cancer-specific distress and perceived self-efficacy in coping with a positive genetic test result among persons at risk of having deleterious p53 mutations. METHODS: One hundred thirty-five persons from 15 LFS-affected families were invited to take part in a study that offered p53 genetic counseling and testing and to complete psychosocial measures. RESULTS: Participants (n=92) were more likely to be younger and female than nonparticipants (n=43). In multivariate analyses, greater cancer-specific distress was associated with having a lower quality of life, a higher perceived risk of having a p53 mutation, no personal history of cancer and a greater number of first degree relatives (FDRs) affected with cancer. Lower perceived self-efficacy in coping with a positive test result was associated with greater cancer worry, higher decisional conflict about p53 testing and having no personal history of cancer. CONCLUSIONS: Individual perceptions about cancer risk and p53 genetic testing, as well as personal experience with FDRs' cancer diagnoses and deaths, should be addressed during the counseling and testing process for LFS-affected families.


Assuntos
Aconselhamento Genético/métodos , Síndrome de Li-Fraumeni/genética , Neoplasias/diagnóstico , Neoplasias/genética , Mutação Puntual/genética , Adaptação Psicológica , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Conflito (Psicologia) , Tomada de Decisões , Feminino , Seguimentos , Genes p53 , Humanos , Pessoa de Meia-Idade , Qualidade de Vida/psicologia , Fatores de Risco , Autoeficácia , Inquéritos e Questionários , Adulto Jovem
10.
Fam Cancer ; 7(3): 267-74, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18283560

RESUMO

OBJECTIVE: To determine the value of histology in identifying Lynch syndrome among those patients with early onset of colorectal cancer (CRC). METHODS: Demographic, clinical and cancer history data from patients diagnosed with CRC before 60 years of age, and treated at our institution between 1997 and 2005, were collected from medical records and direct interview. Their tumors were assessed to identify histological features suggestive of high frequency microsatellite instability (MSI-H): tumor infiltrating lymphocytes, Crohn's like inflammatory reaction, mucinous, signet ring cells, medullary growth pattern and then, tested for microsatellite instability (MSI) and MLH1/ MSH2 protein expression. RESULTS: Sixty-five patients were included in the study. The mean age at diagnosis was 48 +/- 9.9 years. Overall, 28 (43%) patients, including 13 of 35 diagnosed between ages 50 and 60, had tumor demonstrating one or more histological features suggestive of MSI-H. These patients were younger (45 vs. 50 years, P = 0.02) and more commonly had family history of Lynch syndrome-related cancers (36 vs. 19%), though the latter feature did not reach statistical significance (P = 0.07). Eleven of 25 tumors with MSI-H histology, but only 1 of 29 tumors without special histological features were found to be MSI-H (P < 0.0001). Histology had a positive predictive value of 44% and a negative predictive value of 97% for identifying MSI-H tumors. CONCLUSIONS: Limiting MSI analysis only to those tumors with suggestive histology would have reduced the need for testing by nearly 60% of all tumors from patients that met the revised Bethesda guidelines.


Assuntos
Neoplasias Colorretais Hereditárias sem Polipose/genética , Neoplasias Colorretais Hereditárias sem Polipose/patologia , Fatores Etários , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Fatores de Risco
11.
Genet Med ; 8(4): 226-33, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16617243

RESUMO

PURPOSE: Li-Fraumeni syndrome (LFS) is associated with p53 germline mutations, and carriers are at increased risk for multiple primary cancers. We evaluated outcomes following the administration of a video-based decision aid (DA) prior to clinical p53 genetic counseling and testing among persons who had previously participated in cancer genetics research. METHODS: Fifty-seven individuals at risk for a known p53 mutation completed baseline and post-DA measures of psychological outcomes, plus knowledge and attitudes regarding p53 genetic testing. Counseling and testing uptake also was recorded. RESULTS: At baseline, multivariate analysis showed that greater testing intention was associated with lower decisional conflict (P < 0.01). Compared with baseline data, multivariate analyses of post-DA outcomes showed that knowledge about LFS and genetic testing increased and decisional conflict related to testing decreased (P < 0.001). Mean cancer worries scores decreased among all participants (P < 0.001), and mean depression scores decreased for males (P < 0.05). Thirty-nine (68%) completed pre-test genetic counseling and 23 (40%) subsequently gave a blood sample for clinical genetic testing. CONCLUSION: This intervention was useful as an initial outreach and educational method for families considering p53 genetic testing, and may improve knowledge about LFS as well as psychological outcomes.


Assuntos
Tomada de Decisões , Técnicas de Apoio para a Decisão , Família/psicologia , Aconselhamento Genético/psicologia , Testes Genéticos/psicologia , Adulto , Idoso , Feminino , Predisposição Genética para Doença/psicologia , Humanos , Síndrome de Li-Fraumeni/genética , Síndrome de Li-Fraumeni/prevenção & controle , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Mutação , Avaliação de Resultados (Cuidados de Saúde) , Participação do Paciente , Proteína Supressora de Tumor p53/genética
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