Germline mutation profile among Hispanic women with epithelial ovarian cancer (EOC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 1584-1584
Author(s):  
Yanin Chavarri Guerra ◽  
Jeffrey N. Weitzel ◽  
Kathleen Reilly Blazer ◽  
Thomas Paul Slavin ◽  
Rosa Mejia ◽  
...  
Keyword(s):  
Germline Mutation ◽  
Cancer Genomics ◽  
Research Network ◽  
Cancer Risk Assessment ◽  
Community Research ◽  
Underrepresented Populations ◽  
Similar Frequency ◽  
Mutation Profile ◽  
Brca1 Brca2 ◽  
The U.S

1584 Background: Hospital-based studies have reported a 15% prevalence of BRCA1/ BRCA2( BRCA) mutations, with a slightly higher yield of other predisposition genes on multigene panel testing (MGPT) among women with EOC, and National Comprehensive Cancer Network guidelines recommend genetic cancer risk assessment for women with EOC. However, there is limited data about the genetic epidemiology of EOC among underrepresented populations, such as Hispanics. Consequently, we determined the germline mutation profile of Hispanics with EOC, and compared them with non-Hispanics. Methods: We included all women with a personal history of EOC from the U.S. and Latin America (LatAm; Mexico, Colombia, and Peru), enrolled in the Clinical Cancer Genomics Community Research Network registry. We assessed the prevalence of pathogenic variants (PV) in BRCA1/ BRCA2( BRCA) and other genes, contrasting the germline mutation profile between Hispanics living in LatAm, U.S. Hispanics, women of Ashkenazi Jewish (AJ) ancestry in the US, and other U.S. non-Hispanics. Results: Among 1186 women with EOC (209 from LatAm, 254 U.S. Hispanics l, 78 AJ, and 645 other non-Hispanic), 262 (22%) had a PV in BRCAgenes. Hispanics from LatAm and the U.S. had a similar frequency of BRCAmutations to AJ (30.6%, 29.9%, and 38.4%, respectively; p = 0.14); while non-Hispanics showed a significantly lower frequency of BRCAmutations (14.2%, p = 0.03). The most frequently mutated gene was BRCA1(n = 197, 74.6%), followed by BRCA2(n = 67, 25.3%). Among BRCA-negative cases (n = 924), 59% (n = 545) were evaluated by MGPT and PVs were identified in 2.9% [6 Hispanics (1.2%), 3 AJ (3.8%) and 26 Non-Hispanics (4%)]), of which 66% (n = 23) were in mismatch repair genes ( MSH2, MLH1, MSH6, PMS2), and 34% (n = 12) in other EOC-associated genes ( BRIP1, NBN, PALB2, RAD51C, and RAD51D). Clinically actionable PVs in ATM (n = 4; 0.3% ) and CHEK2 (n = 6; 0.5% ) were also observed. Conclusions: Hispanics with EOC have an elevated frequency of PV, similar to that of classic founder populations such as AJ, and significantly higher than other non-Hispanics. This is partially explained by a high prevalence of recurrent LatAm-specific PV, highlighting the importance of conducting genetic studies in underrepresented populations. There was modest incremental benefit of MGPT.

Enhancing access to genetic cancer risk assessment (GCRA) in Monterrey, Mexico: The beginning of a prevention program.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e13150-e13150
Author(s):  
Dione Aguilar y Méndez ◽  
Jeffrey N. Weitzel ◽  
Kathleen Reilly Blazer ◽  
Danielle Castillo ◽  
Josef Herzog ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Reduction ◽  
Prevention Program ◽  
Cancer Genomics ◽  
Limited Resource ◽  
Research Network ◽  
Cancer Risk Assessment ◽  
Community Research ◽  
Cancer Center ◽  
Cascade Testing

e13150 Background: In limited-resource countries like Mexico, GCRA is not routinely provided due to elevated costs, lack of public coverage for testing and prophylactic surgeries, and limited GCRA expertise or awareness among providers and patients. Thus, GCRA services in Mexico are 20 years behind higher income countries, resulting in suboptimal care and limited opportunity for prevention. The Breast Cancer Center TecSalud established formal GCRA services for underserved patients by recruiting a cancer geneticist who provides care at no added expense to patients, building academic collaborations for training and research with City of Hope, and enabling free genetic testing through the Clinical Cancer Genomics Community Research Network, supported in part by the Breast Cancer Research Foundation. Aim: To report the uptake of the GCRA program by patients and relatives at TecSalud from January 2016 - December 2018. Methods: Eligibility includes Mexican women who meet hereditary breast cancer testing criteria and family members of mutation carriers. Risk reduction procedures are covered by Seguro Popular and/or the NGO Fundación Santos y de la Garza Evia. Results: GCRA was offered to 255 patients and 74 at risk relatives, with an increasing reach (proportion of those eligible who access the program). A significant growth of cascade testing and access to risk reduction surgery over time are noted. Conclusions: A growing number of referrals and GCRA visits shows improving reach, possibly due to engagement of the multidisciplinary team and increased patient awareness. The expansion of cascade testing and performance of risk-appropriate surgeries reflects a maturing prevention program. Key determinants of our progress are collaborations that provided us with crucial mentorship, access to genetic assays, as well as the increasing involvement of local leaders, administrators and benefactors for the establishment of vital clinical and research capacity. Multilevel efforts should continue to enhance the delivery of standard of medical care for the most vulnerable and underserved high-risk patients and families. [Table: see text]

scholarly journals Genetic epidemiology of BRCA1- and BRCA2-associated cancer across Latin America

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Josef S. Herzog ◽  
Yanin Chavarri-Guerra ◽  
Danielle Castillo ◽  
Julio Abugattas ◽  
Cynthia Villarreal-Garza ◽  
...  
Keyword(s):  
Latin America ◽  
Latin American ◽  
Cancer Genomics ◽  
Low Cost ◽  
Probability Model ◽  
Copy Number Variant ◽  
Research Network ◽  
Community Research ◽  
Brca1 And Brca2 ◽  
Pathogenic Variants

AbstractThe prevalence and contribution of BRCA1/2 (BRCA) pathogenic variants (PVs) to the cancer burden in Latin America are not well understood. This study aims to address this disparity. BRCA analyses were performed on prospectively enrolled Latin American Clinical Cancer Genomics Community Research Network participants via a combination of methods: a Hispanic Mutation Panel (HISPANEL) on MassARRAY; semiconductor sequencing; and copy number variant (CNV) detection. BRCA PV probability was calculated using BRCAPRO. Among 1,627 participants (95.2% with cancer), we detected 236 (14.5%) BRCA PVs; 160 BRCA1 (31% CNVs); 76 BRCA2 PV frequency varied by country: 26% Brazil, 9% Colombia, 13% Peru, and 17% Mexico. Recurrent PVs (seen ≥3 times), some region-specific, represented 42.8% (101/236) of PVs. There was no ClinVar entry for 14% (17/125) of unique PVs, and 57% (111/196) of unique VUS. The area under the ROC curve for BRCAPRO was 0.76. In summary, we implemented a low-cost BRCA testing strategy and documented a significant burden of non-ClinVar reported BRCA PVs among Latin Americans. There are recurrent, population-specific PVs and CNVs, and we note that the BRCAPRO mutation probability model performs adequately. This study helps address the gap in our understanding of BRCA-associated cancer in Latin America.

scholarly journals Genetic Gastric Cancer Susceptibility in the International Clinical Cancer Genomics Community Research Network

2017 ◽  
Vol 216-217 ◽  
pp. 111-119 ◽  
Author(s):  
Thomas Slavin ◽  
Susan L. Neuhausen ◽  
Christina Rybak ◽  
Ilana Solomon ◽  
Bita Nehoray ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Genomics ◽  
Cancer Susceptibility ◽  
Research Network ◽  
Community Research ◽  
Clinical Cancer

Genetic, clinical and pathological characteristics of BRCA-associated breast cancer (BC) in Hispanic patients in the United States (US) and Latin America (LatAm).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1539-1539
Author(s):  
Yanin Chavarri Guerra ◽  
Sharon Sand ◽  
Marcia Cruz Correa ◽  
Pamela Ganschow ◽  
Nancy Cohen ◽  
...  
Keyword(s):  
Cancer Genomics ◽  
Hispanic Women ◽  
The United States ◽  
Research Network ◽  
Community Research ◽  
Brca Mutations ◽  
Younger Age ◽  
The Us ◽  
Hispanic Patients ◽  
History Of

1539 Background: Hispanic women with BC present at a younger age, have a higher frequency of BRCA mutations and show a worse incidence-to-mortality ratio than non-Hispanic women. Information regarding the characteristics of BRCA-associated BC in Hispanics is limited. Here, we assess differences in BRCA-associated BC between Hispanic patients in the US and in LatAm. Methods: Hispanic patients from the US and LatAm (Mexico, Colombia, Peru, and Puerto Rico) with a history of BRCA-associated BC enrolled in the Clinical Cancer Genomics Community Research Network registry were included. We compared the genetic, demographic, clinical and pathologic characteristics between Hispanics from the US and LatAm using Fisher’s exact test and x2statistics. Results: Between 1997 and 2016, 3670 Hispanic patients with a history of BC from LatAm (n = 1341) and the US (n = 2329) were identified, of which 490 (13.3%) had a deleterious BRCA mutation. The frequency of BRCA mutations was similar in Hispanics from LatAm (13.8%, n = 185) and the US (13.1%, n = 305). No significant differences were found in the frequency of BRCA1 vs BRCA2 mutations between patients from LatAm (BRCA1 68%, BRCA2 31.8%) and the US (BRCA1 61.3%, BRCA2 39%) (p = .12). The most frequent mutations found in BRCA1 were: ex 9-12del (LatAm n = 24, US n = 15), 185delAG (LatAm n = 13, US n = 18) and 943ins10 (LatAm n = 3, US n = 8), and in BRCA2 3492insT (LatAm n = 3, US n = 28). Mean age at BC diagnosis was 39.1 (SD 9.5) in LatAm and 41.7 (SD 10.6) in the US (p = 0.01). US patients were significantly more likely to present with Stage 0-II BC than those from LatAm (77.1% vs. 47.6%, p < .001). We found no differences in the proportion of hormone receptor positive tumors between patients from LatAm (45%) and the US (47%) (p = .78). Conclusions: The frequency of BRCA-associated BC was similar between Hispanics in LatAm and the US. Women from LatAm with BRCA mutations present at a younger age, as seen for sporadic BC; the causes for this finding warrant further research. Women with BRCA-associated BC in LatAm are more likely to have advanced BC at presentation, which may be a reflection of disparities and barriers in access to care.

Clinical conundrums: Developing a strategy for discerning TP53-associated chip and coherent clinical care.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 1514-1514
Author(s):  
Jeffrey N. Weitzel ◽  
Judy Ellen Garber ◽  
Danielle Castillo ◽  
Sharon Sand ◽  
Rosa Mejia ◽  
...  
Keyword(s):  
Family History ◽  
Cancer Genomics ◽  
Complete Blood Count ◽  
Clinical Care ◽  
Research Network ◽  
Community Research ◽  
Hematopoietic Malignancy ◽  
Li Fraumeni Syndrome ◽  
Clonal Hematopoiesis ◽  
Pathway Gene

1514 Background: Germline TP53 mutations are associated with Li-Fraumeni syndrome (LFS). However, approximately 20% of commercial laboratory multigene panel test (MGPT)-detected pathogenic TP53 variants represent aberrant clonal expansion (ACE), rather than a germline finding, and are often detected in individuals that lack classic features of LFS. Clonal hematopoiesis (CH) is a form of ACE, and in the absence of an abnormal hemogram is termed Clonal hematopoiesis of indeterminate potential (CHIP). CHIP is often associated with a pathogenic variant (PV) in hematopoietic pathway gene(s) at a variant allele frequency (VAF) less than expected for a heterozygous germline finding. The prevalence increases with age and exposure to chemotherapy. The presence of a skewed VAF is usually noted in a comment on a genetic test result, however, clinicians without genetic training often lack understanding of the comment and need strategies to discern the difference between germline findings, CHIP, and post-zygotic mosaicism. Our studies illuminate possible strategies for discernment for clinicians. Methods: Among 113 cases with MGPT-detected TP53 PVs, enrolled in the Clinical Cancer Genomics Community Research Network registry, we obtained additional tissues, family history and complete blood count (CBC) reports on 42 cases. DNA extracted from formalin fixed paraffin embedded (FFPE) tumor/normal tissues, blood, saliva, eyebrow plucks, was analyzed using a previously validated custom myeloid and CH gene (n = 79) amplicon-based QIAseq panel. PVs with VAF > 2% were included in analyses. Results: Germline status was confirmed for 6 cases (one with a CH PV), post-zygotic mosaicism was supported for 5 cases and 2 were indeterminant. 12 had results supporting ACE/CH, with additional CH-associated PV(s) identified in 5/12 (41%); n = 2 of each TET2, ATM, TP53; and increasing VAF over time for the driver TP53 PV was noted in 2. Of these 2 one was identified to have a hematopoietic malignancy identified through analysis of the CBCs and bone marrow biopsy in parallel with the increasing VAF. Additional results are pending for 7 cases. Conclusions: With the use of our multi-tissue NGS strategy, serial sampling of suspected ACE/CH cases, family history and CBC analyses we were able to discern the status of most TP53 genetic findings. This work has direct translational impact, refining risk estimation and improving the clinical care of patients with TP53 PVs, while avoiding unnecessary LFS-related care and enabling appropriate care for those with ACE.

Communication of genetic testing results and cascade testing among Mexican carriers of cancer-associated variants and their families.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13541-e13541
Author(s):  
Yanin Chavarri Guerra ◽  
Andrés Rodríguez-Faure ◽  
Laura Margarita Bolano Guerra ◽  
Jose Luis Rodriguez Olivares ◽  
Jazmin Arteaga ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Latin American ◽  
Family Involvement ◽  
Medical Information ◽  
Cancer Genomics ◽  
Family Members ◽  
Research Network ◽  
Community Research ◽  
Cascade Testing ◽  
Results Disclosure

e13541 Background: Most hereditary cancer syndromes exhibit autosomal dominant inheritance. Therefore, communicating results to family members and performing cascade testing is crucial in order to identify individuals at risk and offer them appropriate risk-reducing strategies. The process of communicating medical information within families is highly variable and might be affected by several factors (including culture, education, understanding of results, and family conflicts) which remain understudied among individuals living in developing countries. We sought to investigate communication of results and cascade testing reach within the families of Mexican individuals carrying cancer-associated pathogenic variants (PVs). Methods: Individuals seen at a single center in Mexico City carrying a cancer-associated PV and enrolled in the Clinical Cancer Genomics Community Research Network (CCGCRN) were included. Carriers received genetic counseling at the time of results disclosure, a family letter was provided to facilitate the communication of results, and cascade testing was offered. After >3 months from results disclosure, participants were surveyed regarding genetic testing results communication patterns, performance of cascade testing, and surveillance behaviors. Data was analyzed using descriptive statistics. Results: Among 354 probands, 53 (15%) were identified as carriers of a cancer-associated PV. Mean age was 48.3 (range 21-82) years. Cascade testing (≥1 family member) was initiated in 74% of families (n = 39), with a median of 3 (range 0-16) family members tested per proband. 53 carriers responded the survey (29 probands and 24 relatives). 98% (n = 43) had shared results with their family, and 53% (24/45) had shared them with their treating physicians. Most respondents were receiving active surveillance (n = 36, 80%); with 43% (n = 15) reporting having at least one barrier for complying with surveillance (financial: n = 8; distance to the hospital: n = 3). Around half of the carriers perceived their cancer risk to be of ≥50%. Conclusions: Our results show that both the communication of genetic testing results and the proportion of cascade testing within Mexican families are high. Family involvement in health care decision-making is common in Mexico, as in other Latin American countries, which might lead to improved family communication. However, strategies to improve communication with providers are needed in order to tackle barriers and improve surveillance of individuals carrying cancer associated PVs.

scholarly journals Connectivity: insights from the U.S. Long Term Ecological Research Network

Ecosphere ◽  
2021 ◽  
Vol 12 (5) ◽  
Author(s):  
David M. Iwaniec ◽  
Michael Gooseff ◽  
Katharine N. Suding ◽  
David Samuel Johnson ◽  
Daniel C. Reed ◽  
...  
Keyword(s):  
Research Network ◽  
Ecological Research ◽  
Long Term Ecological Research ◽  
The U.S

scholarly journals Risk-adapted approach to prostate cancer screening

2018 ◽  
Vol 14 (2) ◽  
pp. 109-121 ◽  
Author(s):  
A. A. Kirichek ◽  
L. N. Lyubchenko ◽  
V. B. Matveev
Keyword(s):  
Prostate Cancer ◽  
Early Detection ◽  
Germline Mutation ◽  
Prostate Cancer Screening ◽  
Germline Mutations ◽  
Polygenic Inheritance ◽  
Psa Screening ◽  
Psa Testing ◽  
Mutation Carriers ◽  
Brca1 Brca2

Mass prostatic specific antigen (PSA) testing (population-based PSA screening) has remained controversial, nevertheless there are men cohorts likely to benefit from PSA screening. Heritable factors contribute to 60 % risk for developing familial prostate cancer. Despite the fact that its clinical application is challenging due to polygenic inheritance, advances in new generation sequencing technologies permit identifying highly penetrant germline mutations in genes BRCA1, BRCA2, CHEK2, HOXB13 and MMR associated with tremendous increase in risk of developing the prostate cancer. Several germline mutations are associated with clinically aggressiveness of disease and shortened survival. Targeted screening that is based on family history and genomic aberrations should be the next step towards the precision medicine. Men at elevated risk should been performed for early detection are those with familiar history of prostate cancer, or BRCA1, BRCA2, CHEK2, HOXB13 and MMR pathogenic germline mutation carriers, or first line relatives diagnosed with certain types of cancer. Systematic PSA testing in 1–2 years among germline mutation carriers men beginning at age 45 years would contribute to increase in early detection of localized prostate cancer resulting in more chance of curative treatment and improve survival rates

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