Dissecting the genetic heterogeneity of gastric cancer.

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.

Biomarkers of Response to Low-Dose Aspirin in Familial Adenomatous Polyposis Patients.

Background: The results of Aspirin prevention of colorectal adenomas in patients with familial adenomatous polyposis (FAP) are controversial.

Methods: We conducted a biomarker-based clinical study in eight FAP patients treated with enteric-coated low-dose Aspirin (100 mg daily for three months) to explore whether the drug targets mainly platelet cyclooxygenase (COX)-1 or affects extraplatelet cellular sources expressing COX-isozymes and/or off-target effects in colorectal adenomas.

Results: In FAP patients, low-dose Aspirin-acetylated platelet COX-1 at Serine529 (>70%) was associated with an almost complete inhibition of platelet thromboxane (TX) B generation ex vivo (serum TXB).

Evidence for PTGER4, PSCA, and MBOAT7 as risk genes for gastric cancer on the genome and transcriptome level.

Genetic associations between variants on chromosome 5p13 and 8q24 and gastric cancer (GC) have been previously reported in the Asian population. We aimed to replicate these findings and to characterize the associations at the genome and transcriptome level. We performed a fine-mapping association study in 1926 GC patients and 2012 controls of European descent using high dense SNP marker sets on both chromosomal regions.

Identification of the tumour transition states occurring during EMT.

In cancer, the epithelial-to-mesenchymal transition (EMT) is associated with tumour stemness, metastasis and resistance to therapy. It has recently been proposed that, rather than being a binary process, EMT occurs through distinct intermediate states. However, there is no direct in vivo evidence for this idea.

Relevance of DNA repair gene polymorphisms to gastric cancer risk and phenotype.

Variations in DNA repair genes have been reported as key factors in gastric cancer (GC) susceptibility but results among studies are inconsistent. We aimed to assess the relevance of DNA repair gene polymorphisms and environmental factors to GC risk and phenotype in a Caucasian population in Spain. Genomic DNA from 603 patients with primary GC and 603 healthy controls was typed for 123 single nucleotide polymorphisms in DNA repair genes using the Illumina platform.

Colonic diverticular disease. Treatment and prevention.

Diverticular disease represents the most common disease affecting the colon in the Western world. Most cases remain asymptomatic, but some others will have symptoms or develop complications. The aims of treatment in symptomatic uncomplicated diverticular disease are to prevent complications and reduce the frequency and intensity of symptoms.

Association of PSCA rs2294008 gene variants with poor prognosis and increased susceptibility to gastric cancer and decreased risk of duodenal ulcer disease.

Two recent genome-wide association studies in Asians have reported the association between the PSCA (prostate stem cell antigen) rs2294008C>T gene polymorphism and two Helicobacter pylori infection-related diseases such as gastric cancer (GC) and duodenal ulcer (DU). Since rs2294008 allele frequencies differ notably among ethnicities, we aimed to assess the role of rs2294008 on the susceptibility to GC and DU in a Caucasian population in Spain. Moreover, the relevance of rs2294008 on GC prognosis was evaluated.

Rate of detection of advanced neoplasms in proximal colon by simulated sigmoidoscopy vs fecal immunochemical tests.

Background & Aims: We compared the ability of biennial fecal immunochemical testing (FIT) and one-time sigmoidoscopy to detect colon side-specific advanced neoplasms in a population-based, multicenter, nationwide, randomized controlled trial.

Methods: We identified asymptomatic men and women, 50-69 years old, through community health registries and randomly assigned them to groups that received a single colonoscopy examination or biennial FIT. Sigmoidoscopy yield was simulated from results obtained from the colonoscopy group, according to the criteria proposed in the UK Flexible Sigmoidoscopy Trial for colonoscopy referral.

Modifiable endoscopic factors that influence the adenoma detection rate in colorectal cancer screening colonoscopies.

Background: Adenoma detection rate (ADR) has become the most important quality indicator for colonoscopy.

Objective: The aim of this study was to investigate which modifiable factors, directly related to the endoscopic procedure, influenced the ADR in screening colonoscopies.

Design: Observational, nested study.

Prognostic role of host cyclooxygenase and cytokine genotypes in a Caucasian cohort of patients with gastric adenocarcinoma.

Background: Genetic factors influencing the prognosis of gastric adenocarcinoma (GAC) are not well known. Given the relevance of cytokines and other pro-inflammatory mediators in cancer progression and invasiveness, we aimed to assess the prognostic role of several functional cytokine and cyclooxygenase gene polymorphisms in patients with GAC.

Methodology: Genomic DNA from 380 Spanish Caucasian patients with primary GAC was genotyped for 23 polymorphisms in pro-inflammatory (IL1B, TNFA, LTA, IL6, IL12p40), anti-inflammatory (IL4, IL1RN, IL10, TGFB1) cytokine, and cyclooxygenase (PTGS1 and PTGS2) genes by PCR, RFLP and TaqMan assays.

Relevance of GSTM1, GSTT1, and GSTP1 gene polymorphisms to gastric cancer susceptibility and phenotype.

Human glutathione S-transferases (GSTs) are phase II metabolizing enzymes that play a key role in protecting against cancer by detoxifying numerous potentially cytotoxic/genotoxic compounds. The genes encoding the human GST isoenzymes GSTM(mu)1, GSTT(theta)1 and GSTP(pi)1 harbour polymorphisms, which have been considered important modifiers of the individual risk for environmentally induced cancers such as gastric cancer (GC). However, results are inconsistent among studies from different geographic areas and ethnic groups.

Management of colonic diverticular disease with poorly absorbed antibiotics and other therapies.

Colonic diverticular disease is common in Western countries and its prevalence increases with age. The large majority of patients (80-85%) will remain entirely asymptomatic throughout their life. In symptomatic cases, most patients will have diverticulosis without inflammation while the remainder will have diverticulitis with or without complications.

Relevance of IL-1 and TNF gene polymorphisms on interleukin-1beta and tumor necrosis factor-alpha gastric mucosal production.

We aimed to evaluate the influence of Helicobacter pylori infection and IL-1/TNF gene polymorphisms on interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha gastric mucosal production. IL-1beta and TNF-alpha levels in homogenized biopsy specimens taken from the antrum and corpus of 81 patients were measured by enzyme-linked immunosorbent assay. Genomic DNA was typed for the IL1B-511, IL1B+3954, variable number of tandem repeat (VNTR) IL1RN, TNFA-308, TNFA-238, LTA NcoI, and LTA Bsi gene polymorphisms by polymerase chain reaction, restriction fragment length polymorphism, and TaqMan assays.

Nonsteroidal anti-inflammatory drugs and lower gastrointestinal complications.

In addition to the upper GI tract, NSAIDs can damage the small bowel and the colon. NSAID enteropathy is frequent and may be present in more than 60% of patients taking these drugs long term. In most cases, damage is subclinical, including increased mucosal permeability, inflammation, erosions, ulceration, but other more serious clinical outcomes such as anemia, and overall bleeding, perforation, obstruction, diverticulitis and deaths have also been described.

Trends in Barrett's esophagus diagnosis in Southern Europe: implications for surveillance.

The incidence of Barrett's esophagus (BE) and esophageal adenocarcinoma has increased in Western countries in recent decades. The aim of this study is to describe the changes in incidence and prevalence of BE diagnosis, dysplasia, and adenocarcinoma development in BE patients in a South-European Mediterranean area. Retrospective population-based analyses of endoscopy and pathology reports from 1976 to 2001 was performed.

Gastric cancer susceptibility is not linked to pro-and anti-inflammatory cytokine gene polymorphisms in whites: a Nationwide Multicenter Study in Spain.

Background And Aims: Recent studies have reported an association between cytokine gene polymorphisms and GC risk. However, results are inconsistent among studies from different geographic regions and ethnic groups. Our goal was to evaluate the influence of Helicobacter pylori (H.

CagA-positive Helicobacter pylori infection is not associated with decreased risk of Barrett's esophagus in a population with high H. pylori infection rate.

Background & Aim: The role that H. pylori infection plays in the development of and Barrett's esophagus (BE) is uncertain. We tested the hypothesis that infection with cagA+ Helicobacter pylori strains protects against the development of BE.