There is a paucity of data on familial risk of developing esophageal adenocarcinoma, gastric cardia adenocarcinoma and distal gastric adenocarcinoma from population-based studies.

To systematically test dietary components for association with serum urate levels and to evaluate the relative contributions of estimates of diet pattern and inherited genetic variants to population variance in serum urate levels.

The objective of this study was to evaluate a pilot program that allowed Chicago field center participants of the Coronary Artery Risk Development in Young Adults (CARDIA) study to submit follow-up information electronically (eCARDIA).

Left atrial appendage (LAA) thrombus has heretofore been considered a contraindication to percutaneous LAA closure (LAAC). Data regarding its management are very limited. The aim of this study was to analyse the medical and invasive treatment of patients referred for LAAC in the presence of LAA thrombus.

Elevated serum urate (SU) concentration is the central risk factor for the development of gout. The aim of this study was to examine the incidence of gout in people with low and normal SU levels (< 7.00 mg/dL).

To examine the association of blood pressure (BP) levels with coronary artery calcium and carotid intima-media thickness (CIMT) in people with maintained BP below the hypertension range based on current definitions.

Race, specifically African ancestry, and obesity are important risk factors for uterine fibroids, and likely interact to provide the right conditions for fibroid growth. However, existing studies largely focus on the main-effects rather than their interaction. Here, we firstly provide evidence for interaction between categories of body mass index (BMI) and reported-race in relation to uterine fibroids. We then investigate whether the association between inferred local European ancestry and fibroid risk is modified by BMI in African American (AA) women in the Vanderbilt University Medical Center bio-repository (BioVU) (539 cases and 794 controls) and the Coronary Artery Risk Development in Young Adults study (CARDIA, 264 cases and 173 controls). We used multiple logistic regression to evaluate interactions between local European ancestry and BMI in relation to fibroid risk, then performed fixed effects meta-analysis. Statistical significance threshold for local-ancestry and BMI interactions was empirically estimated with 10,000 permutations (p-value = 1.18x10-4). Admixture mapping detected an association between European ancestry and fibroid risk which was modified by BMI (continuous-interaction p-value = 3.75x10-5) around ADTRP (chromosome 6p24); the strongest association was found in the obese category (ancestry odds ratio (AOR) = 0.51, p-value = 2.23x10-5). Evaluation of interaction between genotyped/imputed variants and BMI in this targeted region suggested race-specific interaction, present in AAs only; strongest evidence was found for insertion/deletion variant (6:11946435), again in the obese category (OR = 1.66, p-value = 1.72x10-6). We found nominal evidence for interaction between local ancestry and BMI at a previously reported region in chromosome 2q31-32, which includes COL5A2, and TFPI, an immediate downstream target of ADTRP. Interactions between BMI and SNPs (single nucleotide polymorphisms) found in this region in AA women were also detected in an independent European American population of 1,195 cases and 1,164 controls. Findings from our study provide an example of how modifiable and non-modifiable factors may interact to influence fibroid risk and suggest a biological role for BMI in fibroid etiology.

Barrett's esophagus is a common type of metaplasia and a precursor of esophageal adenocarcinoma. However, the cell states and lineage connections underlying the origin, maintenance, and progression of Barrett's esophagus have not been resolved in humans. To address this, we performed single-cell lineage tracing and transcriptional profiling of patient cells isolated from metaplastic and healthy tissue. Our analysis revealed discrete lineages in Barrett's esophagus, normal esophagus, and gastric cardia. Transitional basal progenitor cells of the gastroesophageal junction were unexpectedly related to both esophagus and gastric cardia cells. Barrett's esophagus was polyclonal, with lineages that contained all progenitor and differentiated cell types. In contrast, precancerous dysplastic foci were initiated by the expansion of a single molecularly aberrant Barrett's esophagus clone. Together, these findings provide a comprehensive view of the cell dynamics of Barrett's esophagus, linking cell states along the full disease trajectory, from its origin to cancer.

Long-chain n-3 polyunsaturated fatty acids (PUFAs) can derive from diet or from α-linolenic acid (ALA) by elongation and desaturation. We investigated the association of common genetic variation with plasma phospholipid levels of the four major n-3 PUFAs by performing genome-wide association studies in five population-based cohorts comprising 8,866 subjects of European ancestry. Minor alleles of SNPs in FADS1 and FADS2 (desaturases) were associated with higher levels of ALA (p = 3 x 10⁻⁶⁴) and lower levels of eicosapentaenoic acid (EPA, p = 5 x 10⁻⁵⁸) and docosapentaenoic acid (DPA, p = 4 x 10⁻¹⁵⁴). Minor alleles of SNPs in ELOVL2 (elongase) were associated with higher EPA (p = 2 x 10⁻¹²) and DPA (p = 1 x 10⁻⁴³) and lower docosahexaenoic acid (DHA, p = 1 x 10⁻¹⁵). In addition to genes in the n-3 pathway, we identified a novel association of DPA with several SNPs in GCKR (glucokinase regulator, p = 1 x 10⁻⁸). We observed a weaker association between ALA and EPA among carriers of the minor allele of a representative SNP in FADS2 (rs1535), suggesting a lower rate of ALA-to-EPA conversion in these subjects. In samples of African, Chinese, and Hispanic ancestry, associations of n-3 PUFAs were similar with a representative SNP in FADS1 but less consistent with a representative SNP in ELOVL2. Our findings show that common variation in n-3 metabolic pathway genes and in GCKR influences plasma phospholipid levels of n-3 PUFAs in populations of European ancestry and, for FADS1, in other ancestries.

JKAP modifies T-cell immune response and inflammation, also involves in cardia-cerebrovascular disease etiology. This study intended to explore JKAP's relation with T-helper 1 (Th1), T-helper 17 (Th17) cell levels, clinical properties, and recurrence-free survival (RFS) in acute ischemic stroke (AIS) patients.

Red meat and processed meat are associated with some gastrointestinal cancers. Our study aims to investigate the association of different meat types with esophageal and gastric cancer (EC, GC) in a high-risk population. The Golestan Cohort Study (GCS) is a population-based cohort of 50 045 individuals aged 40 to 75 from northeast Iran. Detailed data on different exposures were collected using validated questionnaires. We considered quintiles of meat consumption, using grams and density (g/1000 kcal/day). We calculated intake of red, processed, organ and white meat, as well as total red meat, including the first three. We used proportional hazards regression models to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for the association between meat types and cancer. During 12 years of follow-up, out of 49 585 participants (57.4% women), 369 developed EC (48.2% women) and 368 developed GC (27.5% women), including 309 esophageal squamous cell, 20 esophageal adenocarcinomas, 216 cardia and 95 non-cardia GC. No association was found for EC except for red meat among females (HR for one quintile increase 1.13, 95% CI = 1.00-1.27). The risk of GC increased for intake of total red meat (HR 1.08, 95% CI = 1.00-1.17) and red meat separately (HR 1.09, 95% CI = 1.00-1.18). The HR for red meat and non-cardia GC was 1.23 (95% CI = 1.02-1.48). No associations were observed for other types of meat. In conclusion, in this high-risk population red meat intake is associated with GC, but not EC, suggesting a substantial role of this modifiable factor in determining the burden of GC.

Eukaryotic translation initiation factor 4E (eIF4E) is deregulated in patients with renal cell carcinoma (RCC) and associated with poor prognosis, and is activated and regulated by Mnk kinases. In this study, we investigated the anti-RCC potential of a unique Mnk inhibitor cercosporamide. We showed that cercosporamide is active against RCC cells via suppressing growth, survival and migration. Combination indices value indicated that the combination of cercosporamide with sunitinib or temsirolimus are synergistic in RCC. In two independent RCC xenograft mouse models, complete tumor growth arrest or reverse was observed throughout the duration of drug treatment in the combination of cercosporamide with sunitinib or temsirolimus groups. Of note, cercosporamide inhibited RCC angiogenesis via negatively regulating a number of RCC endothelial cellular events including morphogenesis, migration, growth and survival. Mechanistically, we found that cercosporamide suppressed pro-angiogenic factors VEGF and HIFα, inhibited EMT and reduced pro-survival and cell cycle proteins; and furthermore this was attributed to cercosporamide's ability in inhibiting eIF4E. This work demonstrates the anti-RCC activity of cercosporamide through targeting both RCC tumor cells and angiogenesis, and provides the first preclinical proof-of-concept of evidence of Mnk inhibition for RCC treatment.

Chronic alcohol use is a risk factor for non-cardia gastric adenocarcinoma. However, it is less well understood whether alcohol use is a risk factor for premalignant mucosal changes, namely gastric intestinal metaplasia. We examined the association between various parameters of alcohol use and risk of gastric intestinal metaplasia.

Obesity is known to be associated with an increased risk of gastric cardia cancer but not with noncardia cancer. In terms of gastric dysplasia, few studies have evaluated its relationship with obesity. In addition, no study on the relationship between obesity and the risk of gastric cancer has analyzed the status of Helicobacter pylori infection.

: Peroral endoscopic myotomy (POEM) is an established modality of treatment for achalasia cardia. Considerable variations exist in the technique of POEM with respect to the length and orientation of the myotomy. In this systematic review and meta-analysis, we compared the outcomes of short versus long myotomy during POEM.

The incidence of proximal gastric cancer in the gastric fundus, cardia, and other parts is increasing rapidly. The purpose of this study was to systematically compare the short-term and long-term clinical effects of proximal gastrectomy with double tract reconstruction (PG-DTR) to total gastrectomy (TG) for proximal early gastric cancer (EGC).

Background The purpose of this study is to analyze potential predisposing factors for a higher risk of recurrence in our esophageal cancer patients managed with neoadjuvant chemotherapy, radiation therapy, and surgery, and to determine their impact on disease-free survival (DFS) and time to recurrence. Methods A total of 154 of 232 patients staged T1b to T4a managed electively at our institute from July 2005 through July 2015 with a tri-modality approach were retrospectively evaluated. Basic demographic, clinical, radiological, operative, and pathological disease-related parameters, along with waiting time for surgery and type of neoadjuvant modality used, were assessed as potential risk factors. The primary endpoint was the impact of these on the risk of recurrence. The secondary endpoint was to study their relation on DFS and time to recurrence. Results The recurrence rate in this particular study was 33.1% over a median follow-up of 35 months (interquartile range = 19-50.3). The median time to recurrence was 12 months, and 94% of recurrences occurred within two years. The median DFS was 33 months, and the one- and three-year DFS was 90% and 72%, respectively. On univariate and multivariate analysis, a complete pathological response (hazard ratio [HR]: 3.8, 95% confidence interval [CI]: 1.41-10.11), negative resection margins (HR: 5.9, 95% CI: 1.69-20.45), and a low nodal index (HR: 6.3, 95% CI: 1.37-28.67 for an index of 0.1-0.2; and HR: 15.2, 95% CI: 0.96-241.73 for an index of >0.2) were found as statistically significant (P = < 0.05) for risk to recurrence. In addition to these three, a low comorbidity index (P = 0.03; HR: 3.5; 95% CI: 1.16-10.52) was an individual positive predictor of DFS. Conclusions A complete pathological response, low nodal index, and margin-negative resection were the identified predictors of freedom from recurrence, with a better DFS and a low comorbidity index as additional indicators of prolonged DFS.

Background: The incidence and characteristics of gastric cancer have been shown to vary widely across Western and Eastern countries. Our study had two aims: to evaluate long-term trends in gastric adenocarcinoma in Japan over a period of 70 years, and to anticipate the future of gastric cancer in Japan, through comparison with data from the United States. Methods: Japanese patient data for 19,306 incident cases of gastric adenocarcinoma from 1946 - 2014 were collected from the Gastric Cancer Database at the Cancer Institute Hospital, Tokyo, Japan (CIH-GCDB). U.S. patient data for 78,625 incident cases of gastric cancer from 1973 - 2012 were obtained from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database. Changes over time in patient and tumor characteristics were investigated in these two cohorts. Results: There was a marked reduction of cancer incidence in the lower third of the stomach in the CIH-GCDB; over 70% to around 30%. The incidence in the upper third has been increasing steadily over time; 3% to 19%, although the number of cardia tumors has not changed. An increase in elderly and obese patients was also noted. In the U.S. population, there was a significant difference in the primary site across races. A notable overall increase in cardia cancer was evident in the Western population during the study period, with no similar change evident in the Japanese population over the last 15 years. In the East Asian population, the proportional frequency of tumors in the cardia was lower and that of tumors in the pyloric antrum was higher. Conclusion: In Japan, cancer in the antrum or pylorus of the stomach has been declining, whereas cancer in the body has been increasing. Unlike the Western population in the United States, adenocarcinoma of esophago-gastric junction is not increasing in Japan.

Background The benefit of adjuvant treatment in gastric adenocarcinoma patients with involvement of the muscularis propria but not beyond is unclear. We aim to establish a model that identifies the factors that adversely affect the prognosis in these patients. Methods We used the Surveillance, Epidemiology, and End Results (SEER) database to identify subjects with stage T2aN0M0 gastric adenocarcinoma who had tumor resection between 2004 and 2015. Data pertaining to the following variables were collected: age, gender, ethnicity, tumor size, grade, site, number of lymph nodes (LNs) being examined, and extent of surgery. Results A total of 1307 patients met our inclusion criteria. The five-year overall survival (OS) was 65%. The following factors were significantly associated with a shorter OS in univariate analysis. Age > 60 years, non-Hispanic whites and non-Hispanic blacks, patients with less than 15 lymph nodes examined at the time of surgery, tumors at the fundus and cardia of the stomach, and those who underwent endoscopic resection or had partial esophagectomy. On multivariate Cox regression, the following factors were predictors for worse OS: age > 60 years with a hazards ratio (HR) = 2.03 (95% CI: 1.49-2.76), patients with less than 15 lymph nodes examined with HR = 1.72 (95% CI: 1.34-2.20), non-Hispanic whites and non-Hispanic blacks with HR = 1.62 (95% CI: 1.26-2.08), and tumors within the cardia and fundus of the stomach with HR = 1.51 (95% CI: 1.21-1.89). Conclusion Patients with stage T2aN0M0 gastric cancer who had their tumor located at the cardia or fundus of the stomach or those with inadequate lymph nodes resection had inferior survival and could potentially benefit from adjuvant chemotherapy.

Chronic Helicobacter pylori (H. pylori) infection promotes non-cardia gastric cancer. Some mouse models suggest that bone marrow derived cells (BMDC) contribute to Helicobacter-associated gastric carcinogenesis. We determined whether this increased susceptibility to Helicobacter-induced gastric carcinogenesis of p27-deficient mice is dependent upon their p27-null BMDC or their p27-null gastric epithelial cells.