Browsing by Author "Faria, R"
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- Increased Risk for Metachronous Gastric Adenocarcinoma Following Gastric MALT Lymphoma-A US Population-Based StudyPublication . Palmela, C; Fonseca, C; Faria, R; Baptista, RB; Ribeiro, S; Ferreira, AOGastric mucosa-associated lymphoid tissue lymphoma (gMALT) and gastric adenocarcinoma (GC) are long-term complications of chronic Helicobacter pylori (HP) gastritis. Treatment of HP infection induces remission in most patients with gMALT. Endoscopic follow-up is not currently endorsed after complete remission. However, the risk of GC in these patients is unclear. OBJECTIVE: The objective of this study is to estimate GC risk in gMALT patients. METHODS: The National Cancer Institute Surveillance, Epidemiology and End Results 13 (SEER) database-Nov 2014 Sub (1992-2012) was used to identify adult patients diagnosed with gMALT between 1992 and 2012. The standardized incidence ratio of second primary GC after a latency period of 12 months was calculated and compared to a reference SEER cohort of identical age, sex and time period. The risk of GC in these patients was also stratified by latency period (five years) and age. RESULTS: We identified 2195 cases of gMALT lymphoma, and 20 (0.91%) of them subsequently developed GC with a relative risk (RR) of 4.32 (95% CI 2.64-6.67) compared to the American population. The median latency time was five years and the risk was maintained afterward (RR 4.92, 95% CI 2.45-8.79). When stratified by age group the risk was highest for the 45-64 group (RR 14.04, 95% CI 5.64-28.93). CONCLUSION: gMALT lymphoma is associated with an increased risk of metachronous gastric adenocarcinoma. The risk is still present after more than five years of follow-up. Further studies may clarify the most adequate follow-up strategy.
- Next-Generation Sequencing of Hereditary Hemochromatosis-Related Genes: Novel Likely Pathogenic Variants Found in the Portuguese PopulationPublication . Faria, R; Silva, B; Silva, C; Loureiro, P; Queiroz, A; Fraga, S; Esteves, J; Mendes, D; Fleming, R; Vieira, L; Gonçalves, J; Faustino, PHereditary hemochromatosis (HH) is an autosomal recessive disorder characterized by excessive iron absorption resulting in pathologically increased body iron stores. It is typically associated with common HFE gene mutation (p.Cys282Tyr and p.His63Asp). However, in Southern European populations up to one third of HH patients do not carry the risk genotypes. This study aimed to explore the use of next-generation sequencing (NGS) technology to analyse a panel of iron metabolism-related genes (HFE, TFR2, HJV, HAMP, SLC40A1, and FTL) in 87 non-classic HH Portuguese patients. A total of 1241 genetic alterations were detected corresponding to 53 different variants, 13 of which were not described in the available public databases. Among them, five were predicted to be potentially pathogenic: three novel mutations in TFR2 [two missense (p.Leu750Pro and p.Ala777Val) and one intronic splicing mutation (c.967-1G>C)], one missense mutation in HFE (p.Tyr230Cys), and one mutation in the 5'-UTR of HAMP gene (c.-25G>A). The results reported here illustrate the usefulness of NGS for targeted iron metabolism-related gene panels, as a likely cost-effective approach for molecular genetics diagnosis of non-classic HH patients. Simultaneously, it has contributed to the knowledge of the pathophysiology of those rare iron metabolism-related disorders.
- Population Genetics of IFITM3 in Portugal and Central Africa Reveals a Potential Modifier of Influenza SeverityPublication . David, S; Correia, V; Antunes, L; Faria, R; Ferrão, J; Faustino, P; Nunes, B; Maltez, F; Lavinha, J; Rebelo de Andrade, HInfluenza epidemics are a serious global public health and economic problem. The IFITM3 allele (rs12252-C) was suggested as a population-based genetic risk factor for severe influenza virus infection by A(H1N1)pdm09. We analyzed the population genetics of IFITM3 variants in the Portuguese general population (n = 200) and Central Africans (largely Angolan) (n = 148) as well as its association to influenza severity in Portuguese patients (n = 41). Seven SNPs, within the 352 bp IFITM3 amplicon around rs12252, were identified. SNP distributions in the Portuguese appeared at an intermediate level between the Africans and other Europeans. According to HapMap, rs34481144 belongs to the same linkage disequilibrium (LD) block as rs12252 and is in strong LD with rs6421983. A negative association with severe relative to mild disease was observed for allele rs34481144-A, indicating a protective effect under the dominant model. Moreover, haplotype Hap4 with rs34481144-A, not including rs12252-C, was significantly associated to mild influenza. Conversely, although with borderline significance, haplotype Hap1 with rs34481144-G, not including rs12252-C, was associated to severe disease. Moreover, in comparison to the general Portuguese population, statistical significant differences in the frequencies of the protective allele rs34481144-A in the severe disease group, the deleterious Hap1 in the mild disease group, and the protective Hap4 in the severe disease group were observed. The population attributable risk (PAR) for the targeted rs34481144 allele or genotype was of 55.91 and 64.44% in the general population and the mildly infected individuals, respectively. Implication of these variants in disease phenotype needs further validation, namely through functional analysis as is discussed.