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- Bousquet, J., et al.
(author)
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Building Bridges for Innovation in Ageing : Synergies between Action Groups of the EIP on AHA
- 2017
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In: The Journal of Nutrition, Health & Aging. - : Springer Nature. - 1279-7707 .- 1760-4788. ; 21:1, s. 92-104
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Journal article (peer-reviewed)abstract
- The Strategic Implementation Plan of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) proposed six Action Groups. After almost three years of activity, many achievements have been obtained through commitments or collaborative work of the Action Groups. However, they have often worked in silos and, consequently, synergies between Action Groups have been proposed to strengthen the triple win of the EIP on AHA. The paper presents the methodology and current status of the Task Force on EIP on AHA synergies. Synergies are in line with the Action Groups' new Renovated Action Plan (2016-2018) to ensure that their future objectives are coherent and fully connected. The outcomes and impact of synergies are using the Monitoring and Assessment Framework for the EIP on AHA (MAFEIP). Eight proposals for synergies have been approved by the Task Force: Five cross-cutting synergies which can be used for all current and future synergies as they consider overarching domains (appropriate polypharmacy, citizen empowerment, teaching and coaching on AHA, deployment of synergies to EU regions, Responsible Research and Innovation), and three cross-cutting synergies focussing on current Action Group activities (falls, frailty, integrated care and chronic respiratory diseases).
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- Vitelli-Storelli, F, et al.
(author)
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Family History and Gastric Cancer Risk: A Pooled Investigation in the Stomach Cancer Pooling (STOP) Project Consortium
- 2021
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In: Cancers. - : MDPI AG. - 2072-6694. ; 13:15
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Journal article (peer-reviewed)abstract
- Although there is a clear relationship between family history (FH) and the risk of gastric cancer (GC), quantification is still needed in relation to different histological types and anatomical sites, and in strata of covariates. The objective was to analyze the risk of GC according to first-degree FH in a uniquely large epidemiological consortium of GC. This investigation includes 5946 cases and 12,776 controls from 17 studies of the Stomach Cancer Pooling (StoP) Project consortium. Summary odds ratios (OR) and the corresponding 95% confidence intervals (CIs) were calculated by pooling study-specific ORs using fixed-effect model meta-analysis techniques. Stratified analyses were carried out by sex, age, tumor location and histological type, smoking habit, socioeconomic status, alcohol intake and fruit consumption. The pooled OR for GC was 1.84 (95% CI: 1.64–2.04; I2 = 6.1%, P heterogeneity = 0.383) in subjects with vs. those without first-degree relatives with GC. No significant differences were observed among subgroups of sex, age, geographic area or study period. Associations tended to be stronger for non-cardia (OR = 1.82; 95% CI: 1.59–2.05 for subjects with FH) than for cardia GC (OR = 1.38; 95% CI: 0.98–1.77), and for the intestinal (OR = 1.92; 95% CI: 1.62–2.23) than for the diffuse histotype (OR = 1.62; 95% CI: 1.28–1.96). This analysis confirms the effect of FH on the risk of GC, reporting an approximately doubled risk, and provides further quantification of the risk of GC according to the subsite and histotype. Considering these findings, accounting for the presence of FH to carry out correct prevention and diagnosis measures is of the utmost importance.
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- Böhm, M., et al.
(author)
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The conservation status of the world’s freshwater molluscs
- 2021
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In: Hydrobiologia. - : Springer Science and Business Media LLC. - 0018-8158 .- 1573-5117. ; 848, s. 3231-3254
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Journal article (peer-reviewed)abstract
- With the biodiversity crisis continuing unchecked, we need to establish levels and drivers of extinction risk, and reassessments over time, to effectively allocate conservation resources and track progress towards global conservation targets. Given that threat appears particularly high in freshwaters, we assessed the extinction risk of 1428 randomly selected freshwater molluscs using the IUCN Red List Categories and Criteria, as part of the Sampled Red List Index project. We show that close to one-third of species in our sample are estimated to be threatened with extinction, with highest levels of threat in the Nearctic, Palearctic and Australasia and among gastropods. Threat levels were higher in lotic than lentic systems. Pollution (chemical and physical) and the modification of natural systems (e.g. through damming and water abstraction) were the most frequently reported threats to freshwater molluscs, with some regional variation. Given that we found little spatial congruence between species richness patterns of freshwater molluscs and other freshwater taxa, apart from crayfish, new additional conservation priority areas emerged from our study. We discuss the implications of our findings for freshwater mollusc conservation, the adequacy of a sampled approach and important next steps to estimate trends in freshwater mollusc extinction risk over time. © 2020, Springer Nature Switzerland AG.
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| 9. |
- Demenais, F, et al.
(author)
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Association of MC1R Variants and Host Phenotypes With Melanoma Risk in CDKN2A Mutation Carriers: A GenoMEL Study.
- 2010
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In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 102, s. 1568-1583
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Journal article (peer-reviewed)abstract
- Background Carrying the cyclin-dependent kinase inhibitor 2A (CDKN2A) germline mutations is associated with a high risk for melanoma. Penetrance of CDKN2A mutations is modified by pigmentation characteristics, nevus phenotypes, and some variants of the melanocortin-1 receptor gene (MC1R), which is known to have a role in the pigmentation process. However, investigation of the associations of both MC1R variants and host phenotypes with melanoma risk has been limited. Methods We included 815 CDKN2A mutation carriers (473 affected, and 342 unaffected, with melanoma) from 186 families from 15 centers in Europe, North America, and Australia who participated in the Melanoma Genetics Consortium. In this family-based study, we assessed the associations of the four most frequent MC1R variants (V60L, V92M, R151C, and R160W) and the number of variants (1, ≥2 variants), alone or jointly with the host phenotypes (hair color, propensity to sunburn, and number of nevi), with melanoma risk in CDKN2A mutation carriers. These associations were estimated and tested using generalized estimating equations. All statistical tests were two-sided. Results Carrying any one of the four most frequent MC1R variants (V60L, V92M, R151C, R160W) in CDKN2A mutation carriers was associated with a statistically significantly increased risk for melanoma across all continents (1.24 × 10(-6) ≤ P ≤ .0007). A consistent pattern of increase in melanoma risk was also associated with increase in number of MC1R variants. The risk of melanoma associated with at least two MC1R variants was 2.6-fold higher than the risk associated with only one variant (odds ratio = 5.83 [95% confidence interval = 3.60 to 9.46] vs 2.25 [95% confidence interval = 1.44 to 3.52]; P(trend) = 1.86 × 10(-8)). The joint analysis of MC1R variants and host phenotypes showed statistically significant associations of melanoma risk, together with MC1R variants (.0001 ≤ P ≤ .04), hair color (.006 ≤ P ≤ .06), and number of nevi (6.9 × 10(-6) ≤ P ≤ .02). Conclusion Results show that MC1R variants, hair color, and number of nevi were jointly associated with melanoma risk in CDKN2A mutation carriers. This joint association may have important consequences for risk assessments in familial settings.
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| 10. |
- Helgadottir, H., et al.
(author)
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Efficacy of novel immunotherapy regimens in patients with metastatic melanoma with germline CDKN2A mutations
- 2020
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In: Journal of Medical Genetics. - : BMJ. - 0022-2593 .- 1468-6244. ; 57:5, s. 316-321
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Journal article (peer-reviewed)abstract
- Background Inherited CDKN2A mutation is a strong risk factor for cutaneous melanoma. Moreover, carriers have been found to have poor melanoma-specific survival. In this study, responses to novel immunotherapy agents in CDKN2A mutation carriers with metastatic melanoma were evaluated. Methods CDKN2A mutation carriers that have developed metastatic melanoma and undergone immunotherapy treatments were identified among carriers enrolled in follow-up studies for familial melanoma. The carriers' responses were compared with responses reported in phase III clinical trials for CTLA-4 and PD-1 inhibitors. From publicly available data sets, melanomas with somatic CDKN2A mutation were analysed for association with tumour mutational load. Results Eleven of 19 carriers (58%) responded to the therapy, a significantly higher frequency than observed in clinical trials (p=0.03, binomial test against an expected rate of 37%). Further, 6 of the 19 carriers (32%) had complete response, a significantly higher frequency than observed in clinical trials (p=0.01, binomial test against an expected rate of 7%). In 118 melanomas with somatic CDKN2A mutations, significantly higher total numbers of mutations were observed compared with 761 melanomas without CDKN2A mutation (Wilcoxon test, p<0.001). Conclusion Patients with CDKN2A mutated melanoma may have improved immunotherapy responses due to increased tumour mutational load, resulting in more neoantigens and stronger antitumorous immune responses.
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- Hess, Timo, et al.
(author)
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Dissecting the genetic heterogeneity of gastric cancer
- 2023
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In: EBioMedicine. - : Elsevier. - 2352-3964. ; 92
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Journal article (peer-reviewed)abstract
- Background: Gastric cancer (GC) is clinically heterogenous according to location (cardia/non-cardia) and histopathology (diffuse/intestinal). We aimed to characterize the genetic risk architecture of GC according to its subtypes. Another aim was to examine whether cardia GC and oesophageal adenocarcinoma (OAC) and its precursor lesion Barrett's oesophagus (BO), which are all located at the gastro-oesophageal junction (GOJ), share polygenic risk architecture.Methods: We did a meta-analysis of ten European genome-wide association studies (GWAS) of GC and its subtypes. All patients had a histopathologically confirmed diagnosis of gastric adenocarcinoma. For the identification of risk genes among GWAS loci we did a transcriptome-wide association study (TWAS) and expression quantitative trait locus (eQTL) study from gastric corpus and antrum mucosa. To test whether cardia GC and OAC/BO share genetic aetiology we also used a European GWAS sample with OAC/BO.Findings: Our GWAS consisting of 5816 patients and 10,999 controls highlights the genetic heterogeneity of GC according to its subtypes. We newly identified two and replicated five GC risk loci, all of them with subtype-specific association. The gastric transcriptome data consisting of 361 corpus and 342 antrum mucosa samples revealed that an upregulated expression of MUC1, ANKRD50, PTGER4, and PSCA are plausible GC-pathomechanisms at four GWAS loci. At another risk locus, we found that the blood-group 0 exerts protective effects for non-cardia and diffuse GC, while blood-group A increases risk for both GC subtypes. Furthermore, our GWAS on cardia GC and OAC/BO (10,279 patients, 16,527 controls) showed that both cancer entities share genetic aetiology at the polygenic level and identified two new risk loci on the single-marker level.Interpretation: Our findings show that the pathophysiology of GC is genetically heterogenous according to location and histopathology. Moreover, our findings point to common molecular mechanisms underlying cardia GC and OAC/BO.
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| 14. |
- Aranda, Carolina Sanchez, et al.
(author)
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Allergic sensitization pattern of patients in Brazil
- 2021
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In: Jornal de Pediatria. - : Elsevier. - 0021-7557 .- 1678-4782. ; 97:4, s. 387-395
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Journal article (peer-reviewed)abstract
- Objective: Allergic sensitization is one of the key components for the development of allergies. Polysensitization seems to be related to the persistence and severity of allergic diseases. Furthermore, allergic sensitization has a predictive role in the development of allergies. The aim of this study was to characterize the pattern of sensitization of atopic patients treated at different pediatric allergy referral centers in Brazil.Methods: A nation-wide transversal multicenter study collected data on patients attended in Brazil. Peripheral blood samples were collected to determine the serum levels of allergen-specific IgE. If allergen-specific IgE was higher than 0.1 kUA/L, the following specific components were quantified.Results: A total of 470 individuals were enrolled in the study. Mite sensitization was the most frequent kind in all participants. A high frequency of sensitization to furry animals and grasses featured in the respiratory allergies. Regarding components, there was a predominance of sensitization to Der p 1 and Der p 2. It has been verified that having a food allergy, atopic dermatitis, or multimorbidity are risk factors for the development of more severe allergic disease.Conclusion: Studies on the pattern of allergic sensitization to a specific population offer tools for the more effectual prevention, diagnosis, and treatment of allergic diseases. Sensitization to dust mites house was the most prevalent in the evaluated sample. High rates of sensitization to furry animals also stand out. Patients with food allergy, atopic dermatitis, or multimorbidity appear to be at greater risk for developing more severe allergic diseases.
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| 19. |
- Gennari, R, et al.
(author)
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Early detection of cancer: ideas for a debate.
- 2007
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In: critical reviews in Oncology Hematology. - : Elsevier BV. - 1040-8428. ; 61, s. 97-103
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Journal article (peer-reviewed)abstract
- Even if the overall number of cancer is increasing, the mortality has started to decrease in the Western World. The role of early detection in this decrease is a matter of debate. To assess its impact on mortality it is important to distinguish between diagnosis of cancer in symptomatic patients, and early detection in asymptomatic individuals who may self-refer or who may be offered ad hoc or systematic screening. The policies for early detection and screening vary greatly between European countries, despite many similarities in their cancer burden, and this partly reflects the uncertainties surrounding asymptomatic testing for cancer. A Task Force of European expert, held in Azzate (VA), Italy, established to address these issues, acknowledged the need for more research in the field of individual risk assessment since general statistics are more and more perceived as inadequate to design personal early detection plans. The group also recognised that combinations of early detection and screening will enforce the effectiveness of new treatments in curbing mortality curves, although policies will vary with different cancers.
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| 20. |
- Yang, Xiaohong R., et al.
(author)
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Multiple rare variants in high-risk pancreatic cancer-related genes may increase risk for pancreatic cancer in a subset of patients with and without germline CDKN2A mutations
- 2016
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In: Human Genetics. - : Springer Science and Business Media LLC. - 0340-6717 .- 1432-1203. ; 135:11, s. 1241-1249
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Journal article (peer-reviewed)abstract
- The risk of pancreatic cancer (PC) is increased in melanoma-prone families but the causal relationship between germline CDKN2A mutations and PC risk is uncertain, suggesting the existence of non-CDKN2A factors. One genetic possibility involves patients having mutations in multiple high-risk PC-related genes; however, no systematic examination has yet been conducted. We used next-generation sequencing data to examine 24 putative PC-related genes in 43 PC patients with and 23 PC patients without germline CDKN2A mutations and 1001 controls. For each gene and the four pathways in which they occurred, we tested whether PC patients (overall or CDKN2A+ and CDKN2A− cases separately) had an increased number of rare nonsynonymous variants. Overall, we identified 35 missense variants in PC patients, 14 in CDKN2A+ and 21 in CDKN2A− PC cases. We found nominally significant associations for mismatch repair genes (MLH1, MSH2, MSH6, PMS2) in all PC patients and for ATM, CPA1, and PMS2 in CDKN2A− PC patients. Further, nine CDKN2A+ and four CDKN2A− PC patients had rare potentially deleterious variants in multiple PC-related genes. Loss-of-function variants were only observed in CDKN2A− PC patients, with ATM having the most pathogenic variants. Also, ATM variants (n = 5) were only observed in CDKN2A− PC patients with a family history that included digestive system tumors. Our results suggest that a subset of PC patients may have increased risk because of germline mutations in multiple PC-related genes.
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