Does race play a role in genetic screening for hereditary cancer syndromes?

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1578-1578
Author(s):  
Sudeshna Chatterjee ◽  
Melissa K Frey ◽  
Zhen Ni Zhou ◽  
Ann Carlson ◽  
Thomas A. Caputo ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Family History ◽  
Cancer Center ◽  
Ashkenazi Jews ◽  
Founder Mutations ◽  
Black Patients ◽  
History Of ◽  
Multigene Panels ◽  
History Of Cancer ◽  
White Patients

1578 Background: Molecular analysis of cancer predisposition genes may influence cancer screening, prevention strategies and options for targeted therapy. We sought to identify ethnic differences in patterns of genetic testing. Methods: Results of all patients with known ancestry who underwent genetic testing at the hereditary breast and ovarian cancer center at a single institution between 7/1/2013-12/31/2016 were reviewed. Race was stratified as Black, White, Asian, and Hispanic. Ashkenazi Jews were excluded from the White subgroup because of their higher rates of testing for deleterious founder mutations. White patients were utilized as the reference population for all statistical analysis. Results: 894 patients were included: 139 Black, 613 White, 33 Hispanic and 108 Asian. Black patients were more likely to undergo genetic testing for a personal history of cancer rather than family history risk assessment compared to White patients (p = 0.002). There was no difference in genetic testing rates based on personal or family history of cancer between Asians or Hispanics and Whites (p = 0.398 ;p = 0.366). Black patients were more likely than White patients to undergo testing with targeted-gene rather than multigene panels (p = 0.026). The use of targeted and multigene panels were not different among Asians or Hispanics ( p = 1.0). Blacks, Asians and Hispanics had a lower rate of known deleterious mutations but a higher rate of variants of unknown significance (VUS) than Whites (15.1% p = 0.048; 22.2% p = .001; 33.3%p = .002 respectively). BRCA1/2 mutations accounted for 100% of identified mutations across all the non-White populations. Among Blacks, BRCA1/2 accounted for 38.1% of VUS compared to 27.9% in Whites ( p = .2114). VUS in the ATM gene accounted for 28.6% in Blacks compared to 8.2% in Whites (p = 0.028). Conclusions: Black patients were less likely to undergo testing based on family history, suggesting a missed opportunity for cancer prevention. They were more likely to undergo targeted testing and100% of identified mutations were in BRCA1/2 genes. Non-white patients had higher rates of VUS, emphasizing the need for improved VUS reclassification in non-White populations.

Racial Disparities in Diffuse Large B Cell Lymphoma: A VA Population Study.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4614-4614
Author(s):  
Sanjay Maraboyina ◽  
Rami S. Komrokji ◽  
Rami Y. Haddad ◽  
Zeina A. Nahleh ◽  
Malek M. Safa
Keyword(s):  
Family History ◽  
Racial Disparities ◽  
Racial Differences ◽  
Wilcoxon Test ◽  
P Value ◽  
Medical Centers ◽  
Black Patients ◽  
History Of ◽  
History Of Cancer ◽  
Large B Cell

Abstract Background: Racial disparities in diffuse large B cell non-Hodgkin’s lymphoma (DLBCL) are not well studied. Racial differences in outcome are not well recognized given majority of patients with DLBCL are white. The VA health care system offers a platform to study those racial differences given similar other variables and socioeconomic status among those patients. Methods: This was a retrospective analysis. The VA Central Cancer Registry (VACCR) database was used to identify patients with DLBCL diagnosed between 1995 and 2005. There are approximately 120 VA medical centers diagnosing and/or treating patients with cancer. The VACCR aggregates the data collected by the medical centers’ cancer registries. Data were extrapolated and analyzed using bio-statistical software SPSS. Variables included age, sex, stage of disease, histology subtype, date of diagnosis, date of last contact, date of relapse, vital status, family history of cancer, tobacco history, alcohol history, Agent orange exposure and whether patients received chemotherapy and or radiation. Independent t test was used for comparing continuous variables and chi square test for categorical variables. Wilcoxon test was used to compare survival among the two groups. Results: There were 2792 patients with DLBCL at the VA system, 2402 white and 323 black patients. Sixty-seven patients from other racial groups were excluded from this analysis. The mean age of presentation among blacks was 57.8 years compared to 65.7 years among whites (P-value < 0.005). More Black patients had history of alcohol use, and smoking. More white patients had family history of cancer. No differences in histology subtypes were observed. Other baseline characteristics were similar. No difference in stage of disease was noted at presentation. IPI score data were not available. Similar proportion of patients received multi-agent chemotherapy among the two groups, 70 % for blacks and 67% for whites (P-value 0.58). Among blacks 16 % of patients received radiation while 19.5 % white patients did (P-value 0.73). The 5-year overall survival for blacks was 24 % compared to 29% for whites (P-value 0.92, Wilcoxon test). No statistically significant differences in survival were noted between the two races within each clinical stage. Using Cox regression multivariable analysis age, stage and chemotherapy were the only statistically significant independent variables affecting survival. Conclusions: DLBCL is less common among blacks. Blacks diagnosed with DLBCL are more likely to present at younger age. The treatment and outcome of DLBCL among blacks are not different from whites within the VA system.

Germline mutations in Brazilian pancreatic carcinoma patients.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16749-e16749
Author(s):  
Livia Munhoz Rodrigues ◽  
Simone Maistro ◽  
Maria Lucia Hirata Katayama ◽  
Luiz A.Senna Leite ◽  
Joao Glasberg ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Genetic Testing ◽  
Family History ◽  
Pancreatic Carcinoma ◽  
Germline Mutations ◽  
Family History Of Cancer ◽  
First Degree Relatives ◽  
Pathogenic Variants ◽  
History Of ◽  
History Of Cancer

e16749 Background: Pancreatic cancer has the prospect of becoming the second leading cause of cancer death by 2030. The NCCN Guidelines recommend genetic testing for all patients with pancreatic cancer, however, the spectrum of germline mutations has not been extensively evaluated because recent studies with genetic testing have explored only a limited number of genes and have focused predominantly on Caucasian populations. Therefore, our objective is to evaluate the frequency and spectrum of germline mutations in unselected patients with pancreatic cancer in a multiethnic population. Methods: Patients from Instituto do Câncer do Estado de São Paulo (Brazil) with histopathological diagnosis of non-endocrine pancreatic carcinoma were included, regardless of the family history of cancer. These patients answered a life habits and family history of cancer questionnaire and supplied blood for the Next Generation Sequencing (MiSeq platform) with the TruSight Hereditary Cancer panel (Illumina), which includes 115 cancer predisposing genes. Variant analysis was performed with the VarStation, a Brazilian tool that offers post-sequencing computational support and aid for clinical interpretation. Results: To the present moment, 77 patients were evaluated. The mean age of the patients was 62 years (27-83), among whom, 13% with young age (≤50 years) and 47 women (61%). Thirty-eight patients (49%) reported cases of cancer in first-degree relatives. Regarding risk factors, 41 patients (53%) reported smoking, 19 (25%) alcohol ingestion and 20 (26%) had obesity. Seven out of 77 patients presented pathogenic variants in ATM (n = 2) , CHEK2, FANCM (n = 2) or PALB2 (n = 2) genes. Two of these patients ( CHEK2 and FANCM) had early onset pancreatic cancer (≤45 years), both denied smoking habit and family history of cancer in 1st degree relatives. Two patients, who were ATM mutation carriers, reported 1st or 2nd degree relatives with cancer and are alive after 4 and 8 years of diagnosis. Conclusions: In this unselected group of pancreatic cancer patients, 15% were young, almost half reported first-degree relatives with cancer and 9% were carriers of pathogenic variants in genes related with the homologous recombination DNA repair.

scholarly journals Implications of ACMG guidelines to identify high-risk acute lymphoblastic leukemia patients with hereditary cancer susceptibility syndromes (HCSS) in a highly consanguineous population

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sara Aslam ◽  
Shabana ◽  
Mehboob Ahmed
Keyword(s):  
Genetic Testing ◽  
Family History ◽  
Cancer Susceptibility ◽  
Lymphoblastic Leukemia ◽  
Early Age ◽  
Pakistani Population ◽  
Parental Consanguinity ◽  
Family History Of Cancer ◽  
History Of ◽  
History Of Cancer

Abstract Background Hereditary cancer susceptibility syndrome (HCSS) contributes to the cancer predisposition at an early age, therefore, identification of HCSS has found to be crucial for surveillance, managing therapeutic interventions and refer the patients and their families for genetic counselling. The study aimed to identify ALL patients who meet the American College of Medical Genetics (ACMG) criteria and refer them for the genetic testing for HCSS as hereditary leukemia and hematologic malignancy syndrome, and to elucidate the significance of high consanguinity with the prevalence of inherited leukemia in Pakistani population. Methods A total of 300 acute lymphoblastic leukemia patients were recruited from the Children’s Hospital, Lahore, Pakistan from December 2018 to September 2019. A structured self-reporting questionnaire based on family and medical history of the disease was utilized for the data collection. Results In our cohort, 60.40% of ALL patients were identified to meet ACMG criteria. Among them, a large number of patients (40.65%) solely fulfil the criteria due to the presence of parental consanguinity. However, parental consanguinity showed protective impact on the onset at early age of disease [OD = 0.44 (0.25–0.77), p-value = 0.00] while, a family history of cancer increased the risk of cardiotoxicity [OD = 2.46 (1.15–5.24), p-value = 0.02]. Parental consanguinity shows no significant impact on the family history of cancer and the number of relatives with cancer. Conclusions More than 50% of the ALL patients were considered the strong candidates’ for genetic testing of HCSS in the Pakistani population, and parental consanguinity was the leading criteria fulfilled by the individuals when assessed through ACMG guidelines. Our study suggests revisiting ACMG guidelines, especially for the criterion of parental consanguinity, and formulating the score based criteria based on; genetic research, the toxicology profile, physical features, personal and family history of cancer for the identification of patients for the genetic testing.

Adult cancer survivorship referrals for hereditary cancer genetic testing.

2018 ◽  
Vol 36 (7_suppl) ◽  
pp. 183-183
Author(s):  
Farzana L. Walcott ◽  
Rebecca Davidson Kaltman ◽  
Elizabeth Hatcher ◽  
Cam Ha ◽  
Tara Biagi ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Family History ◽  
High Risk ◽  
Cancer Survivorship ◽  
Nurse Practitioner ◽  
Hereditary Cancer ◽  
Hereditary Cancer Syndromes ◽  
History Of ◽  
Cancer Syndromes ◽  
History Of Cancer

183 Background: Genetic testing for hereditary cancer syndromes is underutilized among cancer patients. Cancer survivorship clinics may identify individuals at risk for hereditary cancer. We present the number of referrals from George Washington (GW) Adult Cancer Survivorship Clinic (ACS) to the GW Ruth Paul Hereditary Cancer Program (RPHCP) to demonstrate the feasibility of identifying high risk individuals in cancer survivorship. Methods: We reviewed the number of patients seen at the GW ACS and subsequent referrals to the GW RPHCP for genetic counseling/testing. An IRB approved research registry was used for retrieval of the data. The ACS clinic is staffed by a physician internist trained in clinical cancer genetics and a nurse practitioner trained in cancer survivorship. Results: 261 patients were seen in ACS from January 1, 2016, to September 30, 2017. Twenty patients (7.6%) were referred to RPHCP based on personal/family cancer history. Three patients were not consented for the research registry, leaving a total of 17 patients for this analysis. Fifteen (88.2%) patients were referred by the physician and 2/17 (11.7%) were referred by the nurse practitioner. Sixteen patients had genetic testing (94.1%) and results were: 5/16 (31.2%) positive, 6/16 (37.5%) negative, and 3/16 (18.7%) had a variant of unknown significance (VUS). Results on 2 patients are pending. One patient deferred testing. Of the 17 patients referred, 14/17 (82.3%) had personal/family history of cancer and had seen an oncologist. Cancer sites and germline mutations identified were: bilateral breast cancer and bladder cancer (BRCA2), prostate cancer (MUTYH), breast and ovarian cancer (BRCA1), endometrial cancer (APC). One patient without cancer was referred by an oncologist for a previously identified familial MLH1 mutation, and was positive. Conclusions: Cancer survivorship clinics may identify individuals appropriate for genetic testing for hereditary cancer syndromes. This is likely an underestimate as not all cancer patients are seen in survivorship clinic. Systematic capture of personal and family history of cancer in cancer survivors may enhance utilization of genetic testing services among cancer survivors and identification of high risk individuals.

Supplemental folic acid and/or multivitamins in pregnancy is associated with a decreased risk of childhood and adolescent nasopharyngeal carcinoma

2021 ◽  
pp. 1-6
Author(s):  
Yue Yan ◽  
Chuanbo Xie ◽  
Shi Di ◽  
Zhonghao Wang ◽  
Minqing Wu ◽  
...  
Keyword(s):  
Folic Acid ◽  
Family History ◽  
Nasopharyngeal Carcinoma ◽  
Univariate Analysis ◽  
Cancer Center ◽  
Family History Of Cancer ◽  
History Of ◽  
Maternal Consumption ◽  
Exposures During Pregnancy ◽  
History Of Cancer

Abstract The aim of this study was to evaluate the association between prenatal and neonatal period exposures and the risk of childhood and adolescent nasopharyngeal carcinoma (NPC). From January 2009 to January 2016, a total of 46 patients with childhood and adolescent NPC (i.e., less than 18 years of age) who were treated at Sun Yat-sen University Cancer Center were screened as cases, and a total of 45 cancer-free patients who were treated at Sun Yat-sen University Zhongshan Ophthalmic Center were selected as controls. The association between maternal exposures during pregnancy and obstetric variables and the risk of childhood and adolescent NPC was evaluated using logistic regression analysis. Univariate analysis revealed that compared to children and adolescents without a family history of cancer, those with a family history of cancer had a significantly higher risk of childhood and adolescent NPC [odds ratios (OR) = 3.15, 95% confidence interval (CI) = 1.02–9.75, P = 0.046], and the maternal use of folic acid and/or multivitamins during pregnancy was associated with a reduced risk of childhood and adolescent NPC in the offspring (OR = 0.07, 95% CI = 0.02–0.25, P < 0.001). After multivariate analysis, only the maternal use of folic acid and/or multivitamins during pregnancy remained statistically significant. These findings suggest that maternal consumption of folic acid and/or multivitamins during pregnancy is associated with a decreased risk of childhood and adolescent NPC in the offspring.

Prevalence of pathogenic mutations and variants of uncertain significance in patients undergoing hereditary cancer genetic testing in Cambridge, MA.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e22506-e22506
Author(s):  
Chinmay Jani ◽  
Arashdeep Rupal ◽  
Omar Al Omari ◽  
Lipisha Agarwal ◽  
Katherine A. Stafford ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Family History ◽  
Community Hospital ◽  
Cancer Genetic ◽  
Entire Study ◽  
Variants Of Uncertain Significance ◽  
Pathogenic Mutations ◽  
Uncertain Significance ◽  
History Of ◽  
History Of Cancer

e22506 Background: Genetic testing allows for enhanced prognostication and early intervention in patients with high risk of developing cancer. Genetic testing often reveals variants of uncertain significance (VUS), for which association with disease risk is unclear. The ambiguity of this finding creates a dilemma for patients and providers and has been associated with significant communication error and distress. In this retrospective observational study, we seek to characterize the indications, outcomes, and trends in patients undergoing genetic testing in a community hospital in Cambridge, MA. As our study spanned the beginning of the COVID-19 pandemic, we also assessed its impact on care accessibility. Methods: We included patients undergoing genetic testing at our hospital between December 2019 and October 2020 (n=371). Medical charts were abstracted to identify patient characteristics, family history, indication for genetic testing, genetic findings, and subsequent management. Results: Our population had a mean age of 48 years (SD=15), was predominantly female (88.1%), and had a high proportion of Ashkenazi Jewish descent (15.3%). The vast majority (351, 94.6%) had a family history of cancer, while 123 (33.2%) had a personal history of cancer, most commonly breast (n=89). The most common indications for genetic testing were Hereditary Breast and Ovarian Cancer (HBOC in 280, 75%), Lynch Syndrome (LS in 22, 5.9%), and Familial Adenomatous Polyposis (FAP in 7, 2%). Of patients who met HBOC, LS, or FAP criteria for genetic testing, pathogenic mutations were identified in 9.5% and VUS in 28.6%. Out of total 35 (9.4%) pathogenic mutations found in our entire study population, the most common were in BRCA (9, 25.7%), MUTYH (5, 14.2%), and Lynch genes (3, 8.6%). Out of 103 patients with VUS (27.8%), the most common sites were APC (14) and MSH3 (9). We found no significant trend in genetic counseling consultations over our 11 months study period despite the COVID-19 pandemic (R2 = 0.006). Conclusions: Among patients who met criteria for genetic cancer screening at a community hospital, 9.5% were found to have a pathogenic mutation while 28.6% were found to have VUS. These numbers are comparable to previously published estimates. Despite advances in our understanding of genetic colon and gynecological cancers, the majority of patients presenting for genetic cancer counseling continue to do so due to breast cancer concerns. Lastly, we noted high efficacy in our conversion of in-person genetics consultations to telemedicine during the COVID-19 pandemic, suggesting telemedicine is a robust format for genetic counselling. Mutations (N): BRCA1 (3), BRCA2 (6); MUTHY (5); MSH2 (2), MSH6 (1); ATM (2), and one each in PALB2, RAD50, RAD51C, RAD51D, Tp53, CDKN2A, APC, F2, SDHA, SDHB, VHL. FANCL, NTHL1.

Effect of access to germline genetic testing on pancreatic cancer precision treatment across disease stage and ethnicity.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16783-e16783
Author(s):  
Edward D. Esplin ◽  
Rebecca Truty ◽  
Shan Yang ◽  
Sarah M. Nielsen ◽  
Margaret Klint ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
African American ◽  
Genetic Testing ◽  
Family History ◽  
Germline Mutations ◽  
Disease Stage ◽  
Family History Of Cancer ◽  
History Of ◽  
History Of Cancer ◽  
Multigene Panel

e16783 Background: PARP inhibitor (PARPi) treatment was recently approved for pancreatic cancer (PaCa) patients with germline mutations in 2 DNA damage repair (DDR) genes. Despite criteria recommending germline multigene panel testing for all PaCa patients, barriers to testing remain, including among underserved populations, which limit access to precision therapies. We initiated a sponsored testing program that increases access to germline genetic testing for PaCa in two ways: 1) offering a comprehensive multigene panel, and 2) removing the barrier of cost. Here we present initial results from this program, including the diagnostic yield in patients across stages of PaCa and clinical utility of the findings. Methods: We retrospectively analyzed de-identified data from 966 PaCa patients tested on an 84 gene panel as part of the program to date. The only inclusion criterion was a willingness to participate in the sponsored program by the patient and the provider who ordered the testing. Data included likely pathogenic (LP) and pathogenic (P) mutations, disease stage and ethnicity. Results: In total, 166 (17%) patients were positive for P/LP germline mutations in 30 genes. Mutation rate by ethnicity was: Caucasian 17%, African American 12%, Hispanic 16%, Ashkenazi Jewish 20%, Asian 3%. Only 25% of patients with P/LP variants reported a family history of cancer. There was no statistical difference in mutation rates by stage (p = 0.11) [Table]. In positive patients, 83 (78%) had mutations conferring potential eligibility for DDR gene-specific precision therapies or clinical treatment trials. 28 (26%) were potentially eligible for olaparib due to BRCA1/2 mutations, 8 (7%) were potentially eligible for pembrolizumab, and 47 (44%) for PARPi clinical trials. Conclusions: This study found 8.5% of all PaCa patients tested are potentially eligible for germline-based precision therapies and/or clinical treatment trials. Of mutation positive patients, 75% did not report a family history of cancer. The positive rate was not statistically different between patients with stage I and stage IV PaCa, underscoring the recommendation to test all patients with PaCa. This program had a 1.5% increased relative uptake among African American patients compared to a standard insurance reimbursement delivery model. These data suggest reducing barriers improves PaCa patient access to genetic information that enables precision therapy. [Table: see text]

scholarly journals Undifferentiated Pleomorphic Sarcoma of the Spine in a patient with Li-Fraumeni syndrome: a case report

2020 ◽  
Author(s):  
Linxiang Zhang ◽  
Jijie Yan ◽  
Guangjian Bai ◽  
Yiwei Hu ◽  
Lijun Jiang ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Family History ◽  
Male Patient ◽  
Secondary Cancer ◽  
Li Fraumeni Syndrome ◽  
Pleomorphic Sarcoma ◽  
History Of ◽  
Aggressive Tumor ◽  
Li Fraumeni ◽  
History Of Cancer

Abstract Background Undifferentiated pleomorphic sarcoma (UPS) is an aggressive tumor that rarely occurs in the spine. We present a 38-year-old male patient with Li-Fraumeni syndrome and discuss the treatment and prognosis.Case presentation A 38-year-old male patient presented with bilateral lower extremity weakness accompanied by radiation pain. He had been diagnosed with right adrenal cortical carcinoma previously and had a strong family history of cancer. PET/CT indicated increased uptake in many parts of the body, especially the right adrenal gland, the left occipital lobe, and the L4 vertebral body (VB). MRI also revealed the destruction of the L4 vertebral body and a paraspinal soft-tissue mass. The tumor was completely resected and pathological findings revealed UPS. Subsequent genetic testing revealed a mutation in the TP53 gene, which is consistent with Li-Fraumeni syndrome (LFS). The patient received postoperative adjuvant radiotherapy and did not develop local recurrence, metastasis, or secondary cancer during the 31-month follow-up.Conclusions Spinal UPS is a rare aggressive tumor with a poor prognosis. Surgery alone can improve the survival of patients but cannot effectively control the disease. In spinal UPS patients with LFS, we think that the prognostic benefits of postoperative adjuvant therapy outweigh the risks of long-term secondary cancer. Family history of cancer and genetic testing can help diagnose LFS, and MRI of the spine can aid the early detection of microlesions. For these patients, early diagnosis and intervention can effectively improve survival.

scholarly journals Novel SCN5A p.Val1667Asp Missense Variant Segregation and Characterization in a Family with Severe Brugada Syndrome and Multiple Sudden Deaths

2021 ◽  
Vol 22 (9) ◽  
pp. 4700
Author(s):  
Michelle M. Monasky ◽  
Emanuele Micaglio ◽  
Giuseppe Ciconte ◽  
Ilaria Rivolta ◽  
Valeria Borrelli ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Family History ◽  
Risk Stratification ◽  
Brugada Syndrome ◽  
Electrophysiological Study ◽  
Functional Characterization ◽  
The Family ◽  
Novel Variant ◽  
History Of ◽  
Scn5a Gene

Genetic testing in Brugada syndrome (BrS) is still not considered to be useful for clinical management of patients in the majority of cases, due to the current lack of understanding about the effect of specific variants. Additionally, family history of sudden death is generally not considered useful for arrhythmic risk stratification. We sought to demonstrate the usefulness of genetic testing and family history in diagnosis and risk stratification. The family history was collected for a proband who presented with a personal history of aborted cardiac arrest and in whom a novel variant in the SCN5A gene was found. Living family members underwent ajmaline testing, electrophysiological study, and genetic testing to determine genotype-phenotype segregation, if any. Patch-clamp experiments on transfected human embryonic kidney 293 cells enabled the functional characterization of the SCN5A novel variant in vitro. In this study, we provide crucial human data on the novel heterozygous variant NM_198056.2:c.5000T>A (p.Val1667Asp) in the SCN5A gene, and demonstrate its segregation with a severe form of BrS and multiple sudden deaths. Functional data revealed a loss of function of the protein affected by the variant. These results provide the first disease association with this variant and demonstrate the usefulness of genetic testing for diagnosis and risk stratification in certain patients. This study also demonstrates the usefulness of collecting the family history, which can assist in understanding the severity of the disease in certain situations and confirm the importance of the functional studies to distinguish between pathogenic mutations and harmless genetic variants.

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