Agregação Familiar de Cancro Gástrico: Risco Fenotípico e Genotípico

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Agregação Familiar de Cancro Gástrico: Risco Fenotípico e Genotípico

Segunda, 07.10.2013

A agregação familiar de cancro gástrico é responsável por 10% do total de casos, dos quais apenas uma minoria é explicada por mutação germinativa de genes que regulam ou desencadeiam o processo de carcinogénese. Após termos demonstrado um fenótipo gástrico de risco (lesões e condições prémalignas) em estudo caso-controlo efectuado a familiares de primeiro grau de doentes com cancro gástrico precoce (doença antes do 45 anos; Aliment Pharmacol Ther. 2012), demonstramos agora que esse mesmo risco poderá ter como causa a elevada prevalência de infecção por Helicobacter pylori nestes indivíduos, associada a estirpes mais virulentas e resposta desfavorável do hospedeiro à infecção. Este estudo suporta a evidência da erradicação precoce da infecção nestes indivíduos e, possivelmente, rastreio endoscópico.

 

Autores e afiliações:

Ricardo Marcos-Pinto1,2,3,4, Mário Dinis-Ribeiro4,6, Fátima Carneiro3,5, Xiaogang Wen5, Carlos Lopes7,1, Céu Figueiredo3,5, José Carlos Machado3,5, Rui Ferreira3, Celso A. Reis1,3,5, José Ferreira2, Isabel Pedroto1,2, Jorge Areias1,2

 

1. Institute of Biomedical Sciences, University of Porto (ICBAS/UP), Porto, Portugal

2. Department of Gastroenterology, Centro Hospitalar do Porto, University of Porto, Portugal

3. Institute of Molecular Pathology and Immunology of the University of Porto, (IPATIMUP), Porto, Portugal

4. Medical Faculty, University of Porto/CINTESIS, Porto, Portugal

5. Department of Pathology, Centro Hospitalar São João and Medical Faculty, University of Porto, Porto, Portugal

6. Department of Gastroenterology, Portuguese Oncology Institute, Porto, Portugal

7. Department of Pathology, Centro Hospitalar do Porto, Porto, Portugal

 

Abstract:

First-degree relatives (FDR) of early-onset gastric cancer (EOGC) is presumed to be a population with a distinct molecular and phenotypic profile, regarding the prevalence of gastric premalignant conditions and the association with Helicobacter pylori infection and host proinflammatory gene polymorphisms. A case-control study was conducted with FDR of EOGC patients (n = 103) and age and gender matched controls (n = 101; ranging from spouses to neighbors and dyspeptics). Upper endoscopy was performed, Operative Link on Gastritis Assessment (OLGA) system used for staging and H. pylori (cagA and vacA) and host IL1B-511, IL1RN intron2 VNTR and IFNGR1-56 genotyping. Seventy percent of cases showed atrophy, while 19 % presented with high-stage gastritis (OLGA stage III or IV) (p < 0.001); gastric dysplasia was present in seven cases (vs none in controls) (p = 0.007). In cases, H. pylori was present in 82 % (vs 62 % in controls; p = 0.004) with vacA s1 and vacA m1 + strains significantly associated with the presence of atrophy; individuals homozygous for IL1B-511*T present a significantly higher risk for dysplasia. An increased global prevalence of IFNGR1-56*T/*T polymorphism (37 % in cases vs 24 % in controls; p = 0.03) was observed with no association with atrophic changes or dysplasia. All trends observed were kept when comparing FDR of EOGC with spouses, neighbors, or dyspeptic controls. We demonstrated that FDR of EOGC patients have an increased prevalence of high-risk OLGA stages and dysplasia that seem to be associated with high virulence H. pylori strains and pro-inflammatory host genotypes, including a possible population-specific risk marker. FDR of EOGC patients may merit specific management through endoscopic and histopathological adequate assessment of gastric mucosa and surveillance.

 

Revista:

Virchows Arch. 2013 Sep;463(3):391-9. doi: 10.1007/s00428-013-1458-5