title: First-degree relatives of early-onset gastric cancer patients show a high risk for gastric cancer: phenotype and genotype profile.
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.
authors.affiliation: Institute of Biomedical Sciences, University of Porto, Portugal. ricardomarcospinto@sapo.pt
authors.forename: Ricardo
authors.initials: R
authors.lastname: Marcos-Pinto
authors.forename: Mário
authors.initials: M
authors.lastname: Dinis-Ribeiro
authors.forename: Fátima
authors.initials: F
authors.lastname: Carneiro
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Wen
authors.forename: Carlos
authors.initials: C
authors.lastname: Lopes
authors.forename: Céu
authors.initials: C
authors.lastname: Figueiredo
authors.forename: José Carlos
authors.initials: JC
authors.lastname: Machado
authors.forename: Rui M
authors.initials: RM
authors.lastname: Ferreira
authors.forename: Celso A
authors.initials: CA
authors.lastname: Reis
authors.forename: Paulo
authors.initials: P
authors.lastname: Canedo
authors.forename: Cecília
authors.initials: C
authors.lastname: Durães
authors.forename: José
authors.initials: J
authors.lastname: Ferreira
authors.forename: Isabel
authors.initials: I
authors.lastname: Pedroto
authors.forename: Jorge
authors.initials: J
authors.lastname: Areias
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D016022:Case-Control Studies; D005190:Family; D005260:Female; D005838:Genotype; D016481:Helicobacter Infections / Q000175:diagnosis / Q000453:epidemiology / Q000473:pathology; D016480:Helicobacter pylori; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics; D053583:Interleukin-1beta / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics*; D011230:Precancerous Conditions / Q000175:diagnosis / Q000453:epidemiology / Q000473:pathology; D015995:Prevalence; D017471:Receptors, Interferon / Q000235:genetics; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000453:epidemiology* / Q000235:genetics* / Q000473:pathology; D055815:Young Adult; D000096743:Interferon gamma Receptor
chemical_list: D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor; C507763:IL1RN protein, human