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6. Redefinition of familial intestinal gastric cancer: clinical and genetic perspectives

Author

Carvalho, Joana, primary, Oliveira, Patricia, additional, Senz, Janine, additional, São José, Celina, additional, Hansford, Samantha, additional, Teles, Sara Pinto, additional, Ferreira, Marta, additional, Corso, Giovanni, additional, Pinheiro, Hugo, additional, Lemos, Diana, additional, Pascale, Valeria, additional, Roviello, Franco, additional, Huntsman, David, additional, and Oliveira, Carla, additional

Published
2020
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9. Frequency of CDH1 germline mutations in gastric carcinoma coming from high- and low-risk areas: metanalysis and systematic review of the literature

Author

Corso Giovanni, Marrelli Daniele, Pascale Valeria, Vindigni Carla, and Roviello Franco

Subjects
Gastric cancer, E-cadherin, Germline mutation, Risk area, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background The frequency of E-cadherin germline mutations in countries with different incidence rates for gastric carcinoma has not been well established. The goal of this study was to assess the worldwide frequency of CDH1 germline mutations in gastric cancers coming from low- and high-risk areas. Methods English articles using MEDLINE access (from 1998 to 2011). Search terms included CDH1, E-cadherin, germline mutation, gastric cancer, hereditary, familial and diffuse histotype. The study included all E-cadherin germline mutations identified in gastric cancer patients; somatic mutations and germline mutations reported in other tumors were excluded. The method of this study was scheduled in accordance with the "PRISMA statement for reporting systematic reviews and meta-analyses". Countries were classified as low- or middle/high risk-areas for gastric carcinoma incidence. Statistical analysis was performed to correlate the CDH1 mutation frequency with gastric cancer incidence areas. Results A total of 122 E-cadherin germline mutations have been identified; the majority (87.5%) occurred in gastric cancers coming from low-risk areas. In high-risk areas, we identified 16 mutations in which missense mutations were predominant. (68.8%). We verified a significant association between the mutation frequency and the gastric cancer risk area (p < 0.001: overall identified mutations in low- vs. middle/high-risk areas). Conclusions E-cadherin genetic screenings performed in low-risk areas for gastric cancer identified a higher frequency of CDH1 germline mutations. This data could open new approaches in the gastric cancer prevention test; before proposing a proband candidate for the CDH1 genetic screening, geographic variability, alongside the family history should be considered.

Published
2012
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10. Redefinition of familial intestinal gastric cancer: clinical and genetic perspectives.

Author

Carvalho, Joana, Oliveira, Patricia, Senz, Janine, São José, Celina, Hansford, Samantha, Teles, Sara Pinto, Ferreira, Marta, Corso, Giovanni, Pinheiro, Hugo, Lemos, Diana, Pascale, Valeria, Roviello, Franco, Huntsman, David, and Oliveira, Carla

Abstract

Background Familial intestinal gastric cancer (FIGC) remains genetically unexplained and without testing/clinical criteria. Herein, we characterised the age of onset and disease spectrum of 50 FIGC families and searched for genetic causes potentially underlying a monogenic or an oligogenic/polygenic inheritance pattern. Methods Normal and tumour DNA from 50 FIGC probands were sequenced using Illumina custom panels on MiSeq, and their respective germline and somatic landscapes were compared with corresponding landscapes from sporadic intestinal gastric cancer (SIGC) and hereditary diffuse gastric cancer cohorts. Results The most prevalent phenotype in FIGC families was gastric cancer, detected in 138 of 208 patients (50 intestinal gastric cancer probands and 88 unknown gastric cancer histology relatives), followed by colorectal and breast cancers. After excluding benign and intronic variants lacking impact in splicing, 12 rare high-quality variants were found exclusively in 11 FIGC probands. Only two probands carried potentially deleterious variants, but lacked somatic second-hits, weakly supporting the monogenic hypothesis for FIGC. However, FIGC probands developed gastric cancer at least 10 years earlier and carried more TP53 germline common variants than SIGC (p=4.5E-03); FIGC and SIGC could be distinguished by specific germline and somatic variant profiles; there was an excess of FIGC tumours presenting microsatellite instability (38%); and FIGC tumours displayed significantly more somatic common variants than SIGC tumours (p=4.2E-06). Conclusion This study proposed the first data-driven testing criteria for FIGC families, and supported FIGC as a genetically determined, likely polygenic, gastric cancer-predisposing disease, with earlier onset and distinct from patients with SIGC at the germline and somatic levels. [ABSTRACT FROM AUTHOR]

Published
2021
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12. Cardiac eccentric remodeling in patients with rheumatoid arthritis

Author

Pascale, Valeria, primary, Finelli, Rosa, additional, Giannotti, Rocco, additional, Coscioni, Enrico, additional, Izzo, Raffaele, additional, Rozza, Francesco, additional, Caputo, Dario, additional, Moscato, Paolo, additional, Iaccarino, Guido, additional, and Ciccarelli, Michele, additional

Published
2018
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26. Oncogenic mutations in gastric cancer with microsatellite instability

Author

Corso, Giovanni, primary, Velho, Sérgia, additional, Paredes, Joana, additional, Pedrazzani, Corrado, additional, Martins, Diana, additional, Milanezi, Fernanda, additional, Pascale, Valeria, additional, Vindigni, Carla, additional, Pinheiro, Hugo, additional, Leite, Marina, additional, Marrelli, Daniele, additional, Sousa, Sónia, additional, Carneiro, Fátima, additional, Oliveira, Carla, additional, Roviello, Franco, additional, and Seruca, Raquel, additional

Published
2011
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27. Abstract 16382: Length of Food Chain is Crucial in Determining the Impact of Mediterranean Diet on Metabolic Syndrome and Cardiovascular Risk

Author

Santulli, Gaetano, Pascale, Valeria, Finelli, Rosa, Visco, Valeria, Coscioni, Enrico, Giannotti, Rocco, Massari, Angelo, Ciccarelli, Michele, and Iaccarino, Guido

Abstract

Introduction:Substantial evidence has shown that Mediterranean diet can reduce the risk of metabolic syndrome (MS). However, the development of retail distribution has radically changed food supply worldwide. For instance, in the Mediterranean area, industrial retail favors shipments of groceries from regions that are intensive producers of mass food, generating the long supply chain (LSC) of food; on the other hand, short supply chains (SSCs) typically involve local self-producers promoting local markets. To our knowledge, the role of food retail and distribution in the determination of the risk of developing MS has not been studied hitherto.Hypothesis:We hypothesized that food chain length could affect the risk of developing metabolic alterations such as MS in a population accustomed to Mediterranean diet.Methods:We compared the SSC of food, in which aliments are mainly produced in loco, usually with traditional and low-technology methodologies, to the LSC of food. MS was defined using the latest ?Harmonized Criteria? to diagnose MS [CirculationVol.120 (16), Pg.1640]. The study was registered in the ClincalTrial.govdatabase (NCT03305276).Results:We recruited 407 subjects (average age: 56 years; 59% males), all adhering to Mediterranean diet, living in rural or urbanized areas of Southern Italy. The most important source of food in rural areas is represented by locally grown vegetables and meat of courtyard animals (SSC), whereas in metropolitan areas people mainly eat retail food (LSC). The actual dietary habits were confirmed through a validate questionnaire, designed to distinguish SSC and LSC viaa specific score. No significant differences were observed between SSC and LSC groups in terms of common demographic and metabolic parameters. Intriguingly, we found that being on Mediterranean diet with a SSC significantly (p=0.007) reduced the prevalence of MS compared with LSC, a result that was confirmed after correcting for confounding variables.Conclusions:Taken together, our findings show for the first time that the length of food supply chain is an independent predictor of the risk of MS in a population accustomed to Mediterranean diet, supporting the importance of local food environments in the determination of cardiovascular risk.

Published
2019
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28. PIK3CA mutation in gastric cancer and the role of microsatellite instability status in mutations of exons 9 and 20 of the PIK3CA gene

Author

Giandomenico Roviello, Karol Polom, Carla Vindigni, Valeria Pascale, Daniele Marrelli, Daniele Generali, Costantino Voglino, Franco Roviello, Polom, Karol, Marrelli, Daniele, Roviello, Giandomenico, Pascale, Valeria, Voglino, Costantino, Vindigni, Carla, Generali, Daniele, and Roviello, Franco

Subjects
Genetics and Molecular Biology (all), Male, 0301 basic medicine, Oncology, DNA Mutational Analysis, Medicine (miscellaneous), Kaplan-Meier Estimate, Biochemistry, law.invention, Exon, 0302 clinical medicine, law, gastric cancer, PIK3CA, mutation, microsatellite instability, exon, Medicine, Neoplasm, Pharmacology (medical), Genetics (clinical), Polymerase chain reaction, Exons, Middle Aged, 3. Good health, 030220 oncology & carcinogenesis, Mutation (genetic algorithm), Female, Microsatellite Instability, Adult, medicine.medical_specialty, Class I Phosphatidylinositol 3-Kinases, Gastric cancer, Microsatellite instability, Mutation, Biochemistry, Genetics and Molecular Biology (all), General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Stomach Neoplasms, Internal medicine, Internal Medicine, Humans, neoplasms, Pathological, Aged, Proportional Hazards Models, business.industry, Pik3ca mutation, Cancer, medicine.disease, 030104 developmental biology, Reviews and References (medical), business
Abstract

BACKGROUND: A better understanding of molecular gastric cancer (GC) entities may help in tailored treatments of that neoplasm. The PIK3CA mutation is one of the most important in many cancers. OBJECTIVES: We performed a comparison of clinical and pathological data of the PIK3CA mutation in GC patients. MATERIAL AND METHODS: The analysis was done on 472 patients operated on in 1 center. Polymerase chain reaction (PCR) was used for the screening of PIK3CA (exon 9 and 20). For microsatellite instability (MSI) we used 5 quasi-monomorphic mononucleotide repeats - BAT-26, BAT-25, NR-24, NR-21, and NR-27. The clinical and pathological data was analyzed. RESULTS: PIK3CA mutation was observed in 10 out of 472 GC patients (2.1%). Nine out of 10 were MSI (9 of 111 MSI patients - 8.1%). Half of the 10 patients had mutations in exon 9 and the other half in exon 20. A majority of patients with the PIK3CA mutation had MSI (p < 0.001). The 5-year survival of MSI patients with the PIK3CA mutation was 40% and without the mutation, 70.4% (p = 0.309). For patients with the mutation in exon 9, the 5-year survival was 0%, and for those with the mutation in exon 20, 80% (p = 0.031). The Cox proportional hazards regression analysis did not show that PIK3CA is statistically correlated with a worse overall survival. CONCLUSIONS: PIK3CA mutation in GC is a rare finding. It is strongly associated with the MSI molecular subgroup, presenting a worse outcome than other MSI patients. A completely different outcome is associated with the mutation in exon 9 compared to the mutation in exon 20, with the latter being more favorable.

Published
2018

29. We are What We Eat: Impact of Food from Short Supply Chain on Metabolic Syndrome

Author

Rocco Giannotti, Gaetano Santulli, Michele Ciccarelli, Enrico Coscioni, Rosa Finelli, Carmine Morisco, Valeria Visco, Guido Iaccarino, Angelo Massari, Maddalena Illario, Valeria Pascale, Santulli, Gaetano, Pascale, Valeria, Finelli, Rosa, Visco, Valeria, Giannotti, Rocco, Massari, Angelo, Morisco, Carmine, Ciccarelli, Michele, Illario, Maddalena, Iaccarino, Guido, and Coscioni, Enrico

Subjects
cardiovascular risk, Mediterranean diet, Supply chain, Population, Retail distribution, Distribution (economics), mediterranean diet, supply chain of food, metabolic syndrome, food retail, 030204 cardiovascular system & hematology, Article, 03 medical and health sciences, Food chain, 0302 clinical medicine, Food supply, Environmental health, Medicine, 030212 general & internal medicine, education, 2. Zero hunger, education.field_of_study, business.industry, General Medicine, medicine.disease, Metabolic syndrome, business
Abstract

Food supply in the Mediterranean area has been recently modified by big retail distribution; for instance, industrial retail has favored shipments of groceries from regions that are intensive producers of mass food, generating a long supply chain (LSC) of food that opposes short supply chains (SSCs) that promote local food markets. However, the actual functional role of food retail and distribution in the determination of the risk of developing metabolic syndrome (MetS) has not been studied hitherto. The main aim of this study was to test the effects of food chain length on the prevalence of MetS in a population accustomed to the Mediterranean diet. We conducted an observational study in Southern Italy on individuals adhering to the Mediterranean diet. We examined a total of 407 subjects (41% females) with an average age of 56 ± 14.5 years (as standard deviation) and found that being on the Mediterranean diet with a SSC significantly reduces the prevalence of MetS compared with the LSC (SSC: 19.65%, LSC: 31.46%; p: 0.007). Our data indicate for the first time that the length of food supply chain plays a key role in determining the risk of MetS in a population adhering to the Mediterranean diet.

Published
2019

30. Cardiac eccentric remodeling in patients with rheumatoid arthritis

Author

Guido Iaccarino, Paolo Moscato, Francesco Rozza, Michele Ciccarelli, Valeria Pascale, Raffaele Izzo, Rosa Finelli, Dario Caputo, Enrico Coscioni, Rocco Giannotti, Pascale, Valeria, Finelli, Rosa, Giannotti, Rocco, Coscioni, Enrico, Izzo, Raffaele, Rozza, Francesco, Caputo, Dario, Moscato, Paolo, Iaccarino, Guido, and Ciccarelli, Michele

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, Heart Ventricles, Population, lcsh:Medicine, Arthritis, 030204 cardiovascular system & hematology, Article, Anti-Citrullinated Protein Antibodies, Sudden cardiac death, Arthritis, Rheumatoid, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, medicine, Humans, Eccentric, lcsh:Science, Ventricular remodeling, education, Aged, 030203 arthritis & rheumatology, education.field_of_study, Multidisciplinary, Ventricular Remodeling, business.industry, lcsh:R, Heart, Gamma globulin, Middle Aged, medicine.disease, medicine.anatomical_structure, Ventricle, Rheumatoid arthritis, Cardiology, Female, lcsh:Q, gamma-Globulins, business
Abstract

It is known that patients with rheumatoid arthritis (RA) have a higher risk of coronary heart disease and sudden cardiac death. Abnormalities in cardiac geometry appear to be involved in the setting of the cardiovascular risk, but it has never been specifically investigated in RA. We enrolled 44 patients with RA compared to 131 subjects without RA (normal, N): The RA aged between 18 and 70 years (mean 48.3 ± 2.1), 25 females, BMI 27.6 ± 0.9; N, of equal age (48.6 ± 1.2, n.s.), included 80 females (BMI 26.7 ± 0.2, ns). Cardiac Ultrasounds showed an increase of the diameter of the left ventricle but not in the septum with reduction of relative wall thickness (RWT) in the RA population compared to N. Relative wall thickness inversely correlates with biochemical parameters of inflammatory response (gamma globulin, p

Published
2018

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