Differential Proteomic Analysis of Human Saliva using Tandem Mass Tags Quantification for Gastric Cancer Detection.

Novel biomarkers and non-invasive diagnostic methods are urgently needed for the screening of gastric cancer to reduce its high mortality. We employed quantitative proteomics approach to develop discriminatory biomarker signatures from human saliva for the detection of gastric cancer. Salivary proteins were analyzed and compared between gastric cancer patients and matched control subjects by using tandem mass tags (TMT) technology. More than 500 proteins were identified with quantification, and 48 of them showed significant difference expression (p < 0.05) between normal controls and gastric cancer patients, including 7 up-regulated proteins and 41 down-regulated proteins. Five proteins were selected for initial verification by ELISA and three were successfully verified, namely cystatin B (CSTB), triosephosphate isomerase (TPI1), and deleted in malignant brain tumors 1 protein (DMBT1). All three proteins could differentiate gastric cancer patients from normal control subjects, dramatically (p < 0.05). The combination of these three biomarkers could reach 85% sensitivity and 80% specificity for the detection of gastric cancer with accuracy of 0.93. This study provides the proof of concept of salivary biomarkers for the non-invasive detection of gastric cancer. It is highly encouraging to turn these biomarkers into an applicable clinical test after large scale validation

A case-control study of the relationship between gastric cancer and meat consumption in Iran

Background: Despite the descending trends of gastric cancer in many parts of the world, its mortality rate has still remained high globally. Meat, red and processed meat in particular, may induce gastric carcinogenesis through potential mechanisms. However, the role of this dietary aspect in the risk of gastric cancer has not well been investigated so far. Therefore, we designed a study to assess the relation between meat consumption and the risk of gastric cancer in Golestan Province, a high- risk area for gastric malignancies in Iran. Methods: Subjects of this population-based case-control study included 190 histologically confirmed case so fgastric cancer and 647 controls. Meat consumption was evaluated using a 116-item semi-quantitative food frequency questionnaire. A lifestyle questionnaire also collected data concerning demographic features, anthropometric measures, and other known risk factors of gastric cancer. We estimated crude and adjust edoddsratios(ORs) and 95 confidence intervals (CIs) for the relation between meat intake and gastric cancer. Results: After being adjusted for potential confounders, red meat intake was positively associated with gastric cancer which reached statistical significance (OR=1.87, 95 CI: 1.01-3.47, Ptrend = 0.07). On the other hand, individuals in the highest quartile of white meat consumption had astatistically significant reduced risk of gastric cancer compared to those in the lowest quartile (OR = 0.36, 95 CI: 0.19-0.68, Ptrend = 0.005). Conclusions: We observed a positive association between red meat consumption and the risk of gastric cancer, and a reverse relationship regarding white meat intake and the risk of this malignancy

Genome expression analysis by suppression subtractive hybridization identified overexpression of Humanin, a target gene in gastric cancer chemoresistance

Background: In cancer cells, apoptosis is an important mechanism that influences the outcome of chemotherapy and the development of chemoresistance. To find the genes involved in chemoresistance and the development of gastric cancer, we used the suppression subtractive hybridization method to identify the genes that are overexpressed in gastric cancer tissues compared to normal gastric tissues. Results: In the suppression subtractive hybridization library we constructed, the most highly overexpressed genes were humanin isoforms. Humanin is a recently identified endogenous peptide that has anti-apoptotic activity and has been selected for further study due to its potential role in the chemoresistance of gastric cancer. Upregulation of humanin isoforms was also observed in clinical samples by using quantitative real-time PCR. Among the studied isoforms, humanin isoform 3, with an expression level of 4.166 ± 1.44 fold, was the most overexpressed isoform in GC. Conclusions: The overexpression of humanin in gastric cancer suggests a role for chemoresistance and provides new insight into the biology of gastric cancer. We propose that humanin isoforms are novel targets for combating chemoresistance in gastric cancer. © 2014 Mottaghi-Dastjerdi et al.; licensee BioMed Central Ltd

Gastric cancer is the leading cause of death in Italian adult patients with common variable immunodeficiency

An increased prevalence of malignant lymphoma and of gastric cancer has been observed in large cohorts of patients with common variable immunodeficiency (CVID), the most frequently symptomatic primary immunodeficiency. Surveillance strategies for cancers in CVID should be defined based on epidemiological data. Risks and mortality for cancers among 455 Italian patients with CVID were compared to cancer incidence data from the Italian Cancer Registry database. CVID patients showed an increased cancer incidence for all sites combined (Obs = 133, SIR = 2.4; 95%CI = 1.7\u20133.5), due to an excess of non-Hodgkin lymphoma (Obs = 33, SIR = 14.3; 95%CI = 8.4\u201322.6) and of gastric cancer (Obs = 25; SIR = 6.4; 95%CI = 3.2\u201312.5). CVID patients with gastric cancer and lymphoma had a worse survival in comparison to cancer-free CVID (HR: 4.8, 95%CI: 4.2\u201344.4 and HR: 4.2, 95%CI: 2.8\u201344.4). Similar to what observed in other series, CVID-associated lymphomas were more likely to be of B cell origin and often occurred at extra-nodal sites. We collected the largest case-series of gastric cancers in CVID subjects. In contrast to other reports, gastric cancer was the leading cause of death in CVID. Standardized mortality ratio indicated a 10.1-fold excess mortality among CVID patients with gastric cancer. CVID developed gastric cancer 15 years earlier than the normative population, but they had a similar overall survival. Only CVID diagnosed at early stage gastric cancer survived >24 months. Stomach histology from upper endoscopy performed before cancer onset showed areas of atrophic gastritis, intestinal metaplasia or dysplasia. CVID patients might progress rapidly to an advanced cancer stage as shown by patients developing a III-IV stage gastric cancer within 1 year from an endoscopy without signs of dysplasia. Based on high rate of mortality due to gastric cancer in Italian CVID patients, we hereby suggest a strategy aimed at early diagnosis, based on regular upper endoscopy and on Helicobacter pylori infection treatment, recommending an implementation of national guidelines

Increased prevalence of precancerous changes in relatives of gastric cancer patients: critical role of H. pylori

Background & Aims:Helicobacter pylori is believed to predispose to gastric cancer by inducing gastric atrophy and hypochlorhydria. First-degree relatives of patients with gastric cancer have an increased risk of developing gastric cancer. The aim of this study was to determine the prevalence of atrophy and hypochlorhydria and their association with H. pylori infection in first-degree relatives of patients with gastric cancer. Methods:H. pylori status, gastric secretory function, and gastric histology were studied in 100 first-degree relatives of patients with noncardia gastric cancer and compared with those of controls with no family history of this cancer. Results: Compared with healthy controls, relatives of patients with gastric cancer had a higher prevalence of hypochlorhydria (27% vs. 3%) but a similar prevalence of H. pylori infection (63% vs. 64%). Relatives of cancer patients also had a higher prevalence of atrophy (34%) than patients with nonulcer dyspepsia (5%) matched for H. pylori prevalence. Among the relatives of cancer patients, the prevalence of atrophy and hypochlorhydria was increased only in those with evidence of H. pylori infection, was greater in relatives of patients with familial cancer than in relatives of sporadic cancer index patients, and increased with age. Eradication of H. pylori infection produced resolution of the gastric inflammation in each subject and resolution of hypochlorhydria and atrophy in 50% of the subjects. Conclusions: Relatives of patients with gastric cancer have an increased prevalence of precancerous gastric abnormalities, but this increase is confined to those with H. pylori infection. Consequently, prophylactic eradication of the infection should be offered to such subjects

Effective optical identification of type "0-IIb" early gastric cancer with narrow band imaging magnification endoscopy, successfully treated by endoscopic submucosal dissection

Background Endoscopic submucosal dissection (ESD) is currently considered the minimal invasive endoscopic treatment for early gastric cancer. Most superficial gastric neoplastic lesions are depressed type ”0-IIc” (70-80%), while totally flat, classified as type ”0-IIb” early gastric cancer, is rarely reported (0.4%). The aim of the present study was to assess the efficacy of narrow band imaging (NBI) magnification endoscopy in identifying type “0-IIb” early gastric cancer and ESD treatment with curative intention.Methods Twelve of 615 (2%) patients (10 males, median 72 years), treated by ESD at our center, were diagnosed as type “0-IIb” gastric cancer. Ten had exclusively type “0-IIb”, while two had combined types “0-IIb+IIc” and “0-IIa+IIb” gastric cancer. Initial diagnosis was made during screening gastroscopy, while NBI magnification endoscopy combined with indigo-carmine chromoendoscopy were also used.Results White light endoscopy showed only superficial redness. One patient with signet-ring carcinoma showed whitish appearance. Indigo-carmine chromoendoscopy showed better visualization, while NBI magnification endoscopy revealed abnormal mucosal microsurface and microvascular findings which enabled border marking. ESD with curative intention was completed without complications. Histological examination showed complete (R0) resection, in 10 patients (83%). One patient with positive margins received additional surgery (8%). Mean procedure time was 149 (range 60-190) min. One to six years post-ESD all patients remain alive.Conclusions ESD is considered a safe and effective curative treatment for type “0-IIb” gastric cancer, resulting in long-term disease-free survival. NBI magnification endoscopy is effective for accurate optical identification and border marking of type “0-IIb” early gastric cancer

Occurrence of gastric cancer and carcinoids in atrophic gastritis during prospective long-term follow up

Objective. Atrophic gastritis (AG) is a risk condition for gastric cancer and type I gastric carcinoids. Recent studies assessing the overall risk of gastric cancer and carcinoids in AG at long-term follow up are lacking. This study aimed to investigate in a prospective cohort of AG patients the occurrence of gastric cancer and carcinoids at long-term follow up. Methods. A total of 200 AG patients from a prospective cohort (67% female, median age 55 years) with a follow up of 7.5 (range: 4-23.4) years were included. Inclusion criteria were presence of AG and at least one follow-up gastroscopy with biopsies at ≥4 years after AG diagnosis. Follow-up gastroscopies at 4-year intervals were performed. Results. Overall, 22 gastric neoplastic lesions were detected (crude incidence 11%). Gastric cancer was diagnosed in four patients at a median follow up of 7.2 years (crude incidence 2%). Eleven type I gastric carcinoids were detected at a median follow up of 5.1 years (crude incidence of 5.5%). In seven patients, six low-grade and one high-grade dysplasia were found. The annual incidence rate person-year were 0.25% (95% confidence interval [CI]: 0.067-0.63%), 0.43% (95% CI: 0.17-0.89%), and 0.68% (95% CI: 0.34-1.21%) for gastric cancer, dysplasia, and type I-gastric carcinoids, respectively. The incidence rates of gastric cancer and carcinoids were not different (p = 0.07). Conclusion. This study shows an annual incidence rate of 1.36% person-year for gastric neoplastic lesions in AG patients at long-term follow up. AG patients are similarly exposed to gastric cancer and type I gastric carcinoids

Modeling of influential predictors of gastric cancer incidence rates in Golestan Province, North Iran

Golestan province has a reputation for relatively high incidence rates of gastric cancer in Iran. Along with dietary, lifestyle and environmental influential factors, soil selenium and high levels of pesticide used may exert influence in this region. The present study was designed for modeling the influential predictors on incidence of gastric cancer in Golestan. All registered cases of gastric cancer from March 2009 to March 2010 (49 females and 107 males) were investigated. Data were gathered by both check list and researcher made questionnaire (demographic, clinical and lifestyle characteristics) and analysed using logistic regression. Mean (±SD) age at diagnosis was 62.9±13.8 years. CIR and ASR of gastric cancer showed 9.16 and 13.9 per 100,000 people, respectively. Based on univariate logistic regression, a history of smoking (OR= 2.076), unwashed hands after defecation (OR= 2.612), history of cancer in relatives (OR= 2.473), history of gastric cancer in first-degree relatives (OR= 2.278), numbers of gastric cancers in first-degree relatives (OR= 2.078), history of X-ray and dye exposure (OR= 2.395), history of CT scan encounter (OR= 2.915), improper food habits (OR= 3.320), specific eating behavior (OR= 0.740), consumption of probable high risk foods (OR= 2.942), charred flesh (OR= 1.945), and animal fat (OR= 2.716) were confirmed as a risk factors. Changes in lifestyle may be expected to increase gastric cancer incidence dramatically in the near future. Therefore, appropriate educational interventions should be designed and implemented by competent authorities

URETERAL METASTASIS AS THE FIRST MANIFESTATION OF ASYMPTOMATIC GASTRIC CANCER

Ureteral metastasis from gastric cancer is rare. It is usually diagnosed in the setting of an advanced gastric cancer or on postmortem examination. Isolated ureteral metastasis without involvement of other sites is extremely rare. We describe a 67-year-old man with gastric cancer and right ureteral metastasis. The patient was from Ardabil Province, a high incidence area for gastric cancer in Iran. He presented with right flank pain which was found to be due to ureteral obstruction. Surgical relief of the obstruction was sought and the surgical biopsy specimens showed metastatic undifferentiated carcinoma in the ureteral wall. A search for the primary lesion revealed gastric cancer. He denied any symptoms referable to his upper GI tract. The patient is doing well on chemotherapy 6 months after the initial diagnosi

Lifestyle and Gastric Cancer in Iran: Results of a Population Based study

Background: The incidence of gastric cancer has been gradually decreasing worldwide. However, it is still the most common cancer in Iran with wide intra-country variation. Ardabil province in North-West of Iran has been reported to have the highest incidence rate of gastric cancer in Iran with age standardized rate of 49.1 and 25.4 per 100,000 in men and women, respectively. This is one of the highest reported incidences in the world. The aim of this study was to evaluate the influence of lifestyle on the risk of gastric cancer in this high risk area. Methodology: A population based case-control study was conducted to identify reasons for this high rate. 217 cases of gastric cancer were recruited from Ardabil cancer registry. 394 controls were also randomly selected from residents of Ardabil matched for gender and age. Subjects were interviewed using a structured questionnaire. Information on demographic characteristics, dietary habits, tobacco smoking, alcohol consumption, drug abuse and medical and occupational history were collected. Meanwhile 10 ml blood specimen was collected for detection of IgG antibodies against helicobacter pylori using ELISA test which was validated locally. Results: A significantly elevated risk of contracting gastric cancer was observed in drug abusers �OR: 2.50, 95% CI: 1.15 - 5.44� particularly in intestinal type �OR: 3.01, 95% CI: 1.25 - 7.26� without subsite association. This association was attenuated after adjustment for confounders. On the other hand no association was found between gastric cancer and cigarette smoking �OR: 1.17, 95% CI: 0.84 - 1.64� and drinking alcoholic beverage �OR: 1.26, 95% CI: 0.40 - 4.05�. Furthermore in a sub-site analysis, although non-cardia gastric cancer tended to occur in smokers more than non smokers it was not significant. Meanwhile there was no difference between intestinal vs. diffuse type of gastric cancer among smokers. In addition, a higher odds of non filtered cigarettes smoking was seen among cases than controls. Conclusion: our findings provide evidence that in north west of Iran, drug abuse may play a carcinogenic role in the development of gastric cancer, and that smoking and alcohol drinking did not emerge as risk factors