The TP53 Database: transition from the International Agency for Research on Cancer to the US National Cancer Institute.
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ABSTRACT:
SUBMITTER: de Andrade KC
PROVIDER: S-EPMC9090805 | biostudies-literature | 2022 May
REPOSITORIES: biostudies-literature
Publications
The TP53 Database: transition from the International Agency for Research on Cancer to the US National Cancer Institute.
de Andrade Kelvin César KC Lee Elaine E EE Tookmanian Elise M EM Kesserwan Chimene A CA Manfredi James J JJ Hatton Jessica N JN Loukissas Jennifer K JK Zavadil Jiri J Zhou Lei L Olivier Magali M Frone Megan N MN Shahzada Owais O Longabaugh William J R WJR Kratz Christian P CP Malkin David D Hainaut Pierre P Savage Sharon A SA
Cell death and differentiation 20220329 5
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Project description:ImportanceLi-Fraumeni syndrome is a cancer predisposition syndrome that is associated with a high, lifelong risk of a broad spectrum of cancers that is caused by pathogenic TP53 germline variants. A definition that reflects the broad phenotypic spectrum that has evolved since the gene discovery is lacking, and mechanisms leading to phenotypic differences remain largely unknown.ObjectiveTo define the phenotypic spectrum of Li-Fraumeni syndrome and conduct phenotype-genotype associations across the phenotypic spectrum.Design, setting, and participantsWe analyzed and classified the germline variant data set of the International Agency for Research on Cancer TP53 database that contains data on a cohort of 3034 persons from 1282 families reported in the scientific literature since 1990. We defined the term Li-Fraumeni spectrum to encompass (1) phenotypic Li-Fraumeni syndrome, defined by the absence of a pathogenic/likely pathogenic TP53 variant in persons/families meeting clinical Li-Fraumeni syndrome criteria; (2) Li-Fraumeni syndrome, defined by the presence of a pathogenic/likely pathogenic TP53 variant in persons/families meeting Li-Fraumeni syndrome testing criteria; (3) attenuated Li-Fraumeni syndrome, defined by the presence of a pathogenic/likely pathogenic TP53 variant in a person/family with cancer who does not meet Li-Fraumeni syndrome testing criteria; and (4) incidental Li-Fraumeni syndrome, defined by the presence of a pathogenic/likely pathogenic TP53 variant in a person/family without a history of cancer. Data analysis occurred from November 2020 to March 2021.Main outcomes and measuresDifferences in variant distribution and cancer characteristics in patients with a germline TP53 variant who met vs did not meet Li-Fraumeni syndrome testing criteria.ResultsTumor spectra showed significant differences, with more early adrenal (n = 166, 6.5% vs n = 0), brain (n = 360, 14.17% vs n = 57, 7.46%), connective tissue (n = 303, 11.92% vs n = 56, 7.33%), and bone tumors (n = 279, 10.98% vs n = 3, 0.39%) in patients who met Li-Fraumeni syndrome genetic testing criteria (n = 2139). Carriers who did not meet Li-Fraumeni syndrome genetic testing criteria (n = 678) had more breast (n = 292, 38.22% vs n = 700, 27.55%) and other cancers, 45% of them occurring after age 45 years. Hotspot variants were present in both groups. Several variants were exclusively found in patients with Li-Fraumeni syndrome, while others where exclusively found in patients with attenuated Li-Fraumeni syndrome. In patients who met Li-Fraumeni syndrome genetic testing criteria, most TP53 variants were classified as pathogenic/likely pathogenic (1757 of 2139, 82.2%), whereas 40.4% (404 of 678) of TP53 variants identified in patients who did not meet the Li-Fraumeni syndrome genetic testing criteria were classified as variants of uncertain significance, conflicting results, likely benign, benign, or unknown.Conclusions and relevanceThe findings of this cohort study suggest that this new classification, Li-Fraumeni spectrum, is a step toward understanding the factors that lead to phenotypic differences and may serve as a model for other cancer predisposition syndromes.
| S-EPMC8554692 | biostudies-literature
Project description:BackgroundCancer patients and survivors with food insecurity, housing instability, and transportation-related barriers face challenges in access and utilization of quality cancer care thereby adversely impacting their health outcomes. This portfolio analysis synthesized and described National Cancer Institute (NCI)-supported social risk research focused on assessing food insecurity, housing instability, and transportation-related barriers among individuals diagnosed with cancer.MethodsWe conducted a query using the National Institutes of Health iSearch tool to identify NCI-awarded extramural research and training grants (2010-2022). Grant abstracts, specific aims, and research strategies were coded for research characteristics, study population, and outcomes.ResultsOf the 30 grants included in this analysis, most assessed transportation-related barriers as patient-level social needs. Grants focused on community-level social risks, food insecurity, and housing instability were largely absent. Most grants included activities that identified the presence of social risks and/or needs (n = 24), connected patients to social care resources (n = 10), and engaged community members or organizations to inform the research study (n = 9). Of the grants, 18 focused on a single type of cancer, primarily breast cancer, and more than half focused on the treatment and survivorship phases.ConclusionsIn the last decade, there has been limited NCI-funded social risk research grants focused on food insecurity and housing instability. Findings highlight opportunities for future cancer care delivery research, including community and health system-level approaches that integrate social and clinical care to address social risks and social needs. Such efforts can help improve outcomes of populations that experience cancer health and health-care disparities.
| S-EPMC9949593 | biostudies-literature
Project description:Scottish Event Campus, Glasgow, Sunday 4 - Tuesday 6 November 2018 Attendees of the 2018 NCRI Cancer Conference will be able to contact corresponding authors through the Conference App and e-poster platform at the Conference.W: https://conference.ncri.org.uk : E: conference@ncri.org.ukOrganised by the National Cancer Research Institute, which is a partnership of 19 cancer research funders, the NCRI Cancer Conference provides a platform for researchers, clinicians, people affected by cancer and industry representatives to come together to discuss, present and showcase high-quality research. Sponsorship Statement: Publication of this supplement was sponsored by Roche. All content was reviewed and approved by the NCRI Scientific Committee, which held full responsibility for the abstract selection.
| S-EPMC6298386 | biostudies-literature
Project description:BackgroundRapid cycle interventional research can accelerate improvements to cancer care delivery and patient health outcomes by answering multiple questions as part of a single research study. To complement ongoing efforts to increase awareness of and support for rapid cycle interventional research, we conducted a systematic portfolio analysis of research grants funded by the National Cancer Institute on the topic.MethodsWe used standard portfolio analytic methods for identifying, coding, and synthesizing rapid cycle interventional research funded by the National Cancer Institute between 2016 and 2022. A codebook was used to standardize assessment of the grants by common study characteristics, intervention topics, and cancer care delivery context.ResultsWe identified 26 grants, mostly funded since 2019, as rapid cycle interventional research. Most studies included adult or older adult target populations, used electronic systems for intervention delivery, and focused primarily on testing different components of interventions. Studies also used a range of study designs, intervention content areas, cancer sites, and across the cancer control continuum.ConclusionsThe current portfolio analysis of funded rapid cycle interventional research grants suggests a growing albeit relatively small number of studies in this area. Several efforts are needed to continue to grow this area of research, including training programs, funding opportunities, and strengthening research-practice partnerships. This analysis provides a snapshot of current studies and highlights the opportunity for growing this important area of research to optimize cancer care delivery and improve patient outcomes.
| S-EPMC10674048 | biostudies-literature
Project description: Not available
| S-EPMC6891220 | biostudies-literature
Project description:There continues to be a rise in the proportion of resectable non-small cell lung cancer (NSCLC) with the recent expansion of criteria for low-dose lung cancer screening. These are increasingly being treated with minimally invasive techniques. Our study aims to compare outcomes of robotic lobectomy (RL) for NSCLC at a National Cancer Institute-designated Comprehensive Cancer Center (NCI-CCC) to those of open lobectomy (OL), video-assisted thoracoscopic lobectomy (VL), or RL as reported in the National Cancer Database (NCDB). The first 1,021 patients with NSCLC who underwent RL between 2010 and 2020 were matched with peers from the NCDB who had OL, VL, or RL. Matching was performed based on a propensity score calculated by logistic regression using multiple variables. Surgical outcomes included numbers of examined lymph nodes, performance of mediastinal lymphadenectomy, length of stay (LOS), and 30-day mortality. Kaplan-Meier curves and overall survival (OS) were analyzed using log-rank tests. Most common postoperative complications were persistent air leak, atrial fibrillation, and pneumonia. Median LOS was 4 days, and the 30-day mortality rate was 1% (n=10/1,021). Compared to NCDB patients who underwent OL, NCI-CCC patients had a higher mean number of retrieved lymph nodes (P=0.001), higher rate of mediastinal lymphadenectomy (P<0.001), and shorter median LOS (4 vs. 6 days; P<0.001). There was no difference in 30-day mortality (P=0.176). Kaplan-Meier analyses showed no differences in median OS (log-rank P=0.953) or 5-year OS (P=0.774). Compared to NCDB VL, NCI-CCC patients had a higher nodal yield (P<0.001), higher rates of mediastinal lymphadenectomy (P<0.001), and lower conversion rates (4.1% vs. 13.8%, P<0.001). There were no differences in 30-day mortality (P=0.379) or in median LOS (P=0.351). Kaplan-Meier analyses showed no differences in median OS (P=0.720) or 5-year OS (P=0.735). NCI-CCC patients were also matched with NCDB RL patients and had a higher nodal yield (P<0.001), higher rates of mediastinal lymphadenectomy (P<0.001), and lower conversion rates (4.1% vs. 9.5%; P <0.001). There were no differences in 30-day mortality (P=0.899) or in median LOS (P=0.252). Kaplan-Meier analyses showed no differences in median OS (P=0.484) or 5-year OS (P=0.524). RL for NSCLC performed in an NCI-CCC appears to have improved perioperative outcomes with comparable long-term OS compared to national benchmarks in OL and VL.
| S-EPMC10636448 | biostudies-literature
Project description:Organisation EGAO00000001013
| EGAO00000001013 | EGA
Project description:BackgroundNational cancer organizations recommend provision of nutrition, physical activity, and mental health supportive services to cancer survivors. However, the availability of these services across diverse community oncology settings remains unclear.MethodsThe National Cancer Institute Community Oncology Research Program (NCORP) is a national network of community oncology practices engaged in cancer research. The 2022 NCORP Landscape Assessment (5UG1CA189824) assessed individual practices' establishment of survivorship clinics and nutrition, physical activity, and mental health services, resources, and/or referrals. Descriptive statistics summarized and logistic regression quantified the association between services, practice, and patient characteristics.ResultsOf 46 NCORP community sites, 45 (98%) responded to the survey, representing 259 adult practice groups. A total of 41% had a survivorship clinic; 96% offered mental health, 94% nutrition, and 53% physical activity services, resources, and/or referrals. All 3 services were offered in various formats (eg, in-house, referrals, education) by 51% and in-house only by 25% of practices. Practices with advanced practice providers were more likely to have a survivorship clinic (odds ratio [OR] = 3.19, 95% confidence interval [CI] = 1.04 to 9.76). Practices with at least 30% Medicare patients (OR = 2.54, 95% CI = 1.39 to 4.66) and more oncology providers (OR = 1.02, 95% CI = 1.01 to 1.04) were more likely to have all 3 services in any format. Practices with at least 30% Medicare patients (OR = 3.41, 95% CI = 1.50 to 7.77) and a survivorship clinic (OR = 2.84, 95% CI = 1.57 to 5.14) were more likely to have all 3 services in-house.ConclusionsLarger oncology practices and those caring for more survivors on Medicare provided more supportive services, resources, and/or referrals. Smaller practices and those without survivorship clinics may need strategies to address potential gaps in supportive services.
| S-EPMC10868389 | biostudies-literature
Project description:Compelling evidence supports a genetic component to prostate cancer susceptibility and aggressiveness. Recent genome-wide association studies have identified more than 30 single-nucleotide polymorphisms associated with prostate cancer susceptibility. It remains unclear, however, whether such genetic variants are associated with disease aggressiveness--one of the most important questions in prostate cancer research today. To help clarify this and substantially expand research in the genetic determinants of prostate cancer aggressiveness, the first National Cancer Institute Prostate Cancer Genetics Workshop assembled researchers to develop plans for a large new research consortium and patient cohort. The workshop reviewed the prior work in this area and addressed the practical issues in planning future studies. With new DNA sequencing technology, the potential application of sequencing information to patient care is emerging. The workshop, therefore, included state-of-the-art presentations by experts on new genotyping technologies, including sequencing and associated bioinformatics issues, which are just beginning to be applied to cancer genetics.
| S-EPMC3096727 | biostudies-literature
Project description:BackgroundLi-Fraumeni syndrome (LFS) is an autosomal dominant cancer predisposition syndrome characterized by a very high lifetime cancer risk and an early age at diagnosis of a wide cancer spectrum. Precise estimates for the risk of first and subsequent cancers are lacking.MethodsThe National Cancer Institute's Li-Fraumeni Syndrome Study includes families meeting the diagnostic criteria for LFS or Li-Fraumeni-like syndrome, and individuals with a germline TP53 mutation, choroid plexus carcinoma, adrenocortical carcinoma, or ≥3 cancers. Herein, we estimated the cumulative risk and annual hazards for first and second cancers among TP53 mutation carriers (TP53 positive [TP53+]) using MATLAB statistical software.ResultsThis study evaluated 286 TP53+ individuals from 107 families. The cumulative cancer incidence was 50% by age 31 years among TP53+ females and 46 years among males, and nearly 100% by age 70 years for both sexes. Cancer risk was highest after age 20 years for females, mostly due to breast cancer, whereas among males the risk was higher in childhood and later adulthood. Among females, the cumulative incidence rates by age 70 years for breast cancer, soft tissue sarcoma, brain cancer, and osteosarcoma were 54%, 15%, 6%, and 5%, respectively. Among males, the incidence rates were 22%, 19%, and 11%, respectively, for soft tissue sarcoma, brain cancer, and osteosarcoma. Approximately 49% of those with 1 cancer developed at least another cancer after a median of 10 years. The average age-specific risk of developing a second cancer was comparable to that of developing a first cancer.ConclusionsThe cumulative cancer risk in TP53 + individuals was very high and varied by sex, age, and cancer type. Additional work, including prospective risk estimates, is needed to better inform personalized risk management. Cancer 2016;122:3673-81. © 2016 American Cancer Society.
| S-EPMC5115949 | biostudies-literature