Molecular diagnostics in gastric cancer.

Despite recent advances in individualised targeted therapy, gastric cancer remains one of the most challenging diseases in gastrointestinal oncology. Modern imaging techniques using endoscopic filter devices and in vivo molecular imaging are designed to enable early detection of the cancer and surveillance of patients at risk. Molecular characterisation of the tumour itself as well as of the surrounding inflammatory environment is more sophisticated in the view of tailored therapies and individual prognostic assessment. The broad application of high throughput techniques for the description of genome wide patterns of structural (copy number aberrations, single nucleotide polymorphisms, meth…

miR-20b and miR-451a Are Involved in Gastric Carcinogenesis through the PI3K/AKT/mTOR Signaling Pathway: Data from Gastric Cancer Patients, Cell Lines and Ins-Gas Mouse Model

Gastric cancer (GC) is one of the most common and lethal gastrointestinal malignancies worldwide. Many studies have shown that development of GC and other malignancies is mainly driven by alterations of cellular signaling pathways. MicroRNAs (miRNAs) are small noncoding molecules that function as tumor-suppressors or oncogenes, playing an essential role in a variety of fundamental biological processes. In order to understand the functional relevance of miRNA dysregulation, studies analyzing their target genes are of major importance. Here, we chose to analyze two miRNAs, miR-20b and miR-451a, shown to be deregulated in many different malignancies, including GC. Deregulated expression of miR…

Association of Long Non-Coding RNA Polymorphisms with Gastric Cancer and Atrophic Gastritis

Long non-coding RNAs (lncRNA) play an important role in the carcinogenesis of various tumours, including gastric cancer. This study aimed to assess the associations of lncRNA ANRIL, H19, MALAT1, MEG3, HOTAIR single-nucleotide polymorphisms (SNPs) with gastric cancer and atrophic gastritis. SNPs were analyzed in 613 gastric cancer patients, 118 patients with atrophic gastritis and 476 controls from three tertiary centers in Germany, Lithuania and Latvia. Genomic DNA was extracted from peripheral blood leukocytes. SNPs were genotyped by the real-time polymerase chain reaction. Results showed that carriers of MALAT1 rs3200401 CT genotype had the significantly higher odds of atrophic gastritis …

Lack of association between gene polymorphisms of Angiotensin converting enzyme, Nod-like receptor 1, Toll-like receptor 4, FAS/FASL and the presence of Helicobacter pylori-induced premalignant gastric lesions and gastric cancer in Caucasians

Abstract Background Several polymorphisms of genes involved in the immunological recognition of Helicobacter pylori and regulating apoptosis and proliferation have been linked to gastric carcinogenesis, however reported data are partially conflicting. The aim of our study was to evaluate potential associations between the presence of gastric cancer (GC) and high risk atrophic gastritis (HRAG) and polymorphisms of genes encoding Angiotensin converting enzyme (ACE), Nod-like receptor 1 (NOD1), Toll-like receptor 4 (TLR4) and FAS/FASL. Methods Gene polymorphisms were analyzed in 574 subjects (GC: n = 114; HRAG: n = 222, controls: n = 238) of Caucasian origin. ACE I/D (rs4646994), NOD1 796G>…

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

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. Next, we performed expression quantitative trait locus (eQTL) analyses using gastric transcriptome data from 143 individuals focusing on the GC associated variants. On chromosome 5p13 the strongest association was observed at rs6872282 (P = 2.53 x 10(-04)) and on chromosome …

TLR1 and PRKAA1 Gene Polymorphisms in the Development of Atrophic Gastritis and Gastric Cancer.

Background & Aims: Previous genome-wide association studies showed that genetic polymorphisms in toll-like receptor 1 (TLR1) and protein kinase AMP-activated alpha 1 catalytic subunit (PRKAA1) genes were associated with gastric cancer (GC) or increased Helicobacter pylori (H. pylori) infection susceptibility. The aim of this study was to evaluate the association between TLR1 and PRKAA1 genes polymorphisms and H.pylori infection, atrophic gastritis (AG) or GC in the European population.Methods: Single-nucleotide polymorphisms (SNPs) were analysed in 511 controls, 340 AG patients and 327 GC patients. TLR1 C>T (rs4833095) and PRKAA1 C>T (rs13361707) were genotyped by the real-time po…

Gene polymorphisms of micrornas in Helicobacter pylori-induced high risk atrophic gastritis and gastric cancer.

Background and aims MicroRNAs (miRNAs) are known for their function as translational regulators of tumor suppressor or oncogenes. Single nucleotide polymorphisms (SNPs) in miRNAs related genes have been shown to affect the regulatory capacity of miRNAs and were linked with gastric cancer (GC) and premalignant gastric conditions. The purpose of this study was to evaluate potential associations between miRNA-related gene polymorphisms (miR-27a, miR-146a, miR-196a-2, miR-492 and miR-608) and the presence of GC or high risk atrophic gastritis (HRAG) in European population. Methods Gene polymorphisms were analyzed in 995 subjects (controls: n = 351; GC: n = 363; HRAG: n = 281) of European descen…

Detection of cancer through exhaled breath: a systematic review

// Agne Krilaviciute 1 , Jonathan Alexander Heiss 1 , Marcis Leja 2 , Juozas Kupcinskas 3 , Hossam Haick 4 and Hermann Brenner 1,5,6 1 Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany 2 Faculty of Medicine, University of Latvia, Digestive Diseases Center GASTRO, and Riga East University Hospital, Riga, Latvia 3 Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania 4 Department of Chemical Engineering and Russell Berrie Nanotechnology Institute, Technion – Israel Institute of Technology, Haifa, Israel 5 Division of Preventive Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany…

Analysis of the effects of microbiome-related confounding factors on the reproducibility of the volatolomic test.

Volatile organic compound (VOC) testing in breath has potential in gastric cancer (GC) detection. Our objective was to assess the reproducibility of VOCs in GC, and the effects of conditions modifying gut microbiome on the test results. Ten patients with GC were sampled for VOC over three consecutive days; 17 patients were sampled before and after H. pylori eradication therapy combined with a yeast probiotic; 61 patients were sampled before and after bowel cleansing (interventions affecting the microbiome). The samples were analyzed by: (1) gas chromatography linked to mass spectrometry (GC-MS), applying the non-parametric Wilcoxon test (level of significance p    0.05); (2) by cross-reacti…

The Prevalence of Cancer-Associated Autoantibodies in Patients with Gastric Cancer and Progressive Grades of Premalignant Lesions.

Abstract Background: Serum autoantibodies against tumor-associated antigens (TAAs) are detectable in early-stage gastric cancer patients; however, the time point during cancerogenesis when they appear in circulation is still obscure. Methods: In this study, we developed a recombinant antigen microarray and analyzed the prevalence of autoantibodies against 102 TAAs in 829 gastric cancer patients and 929 healthy controls from Caucasian and Asian populations, as well as 100 patients with chronic atrophic gastritis and 775 individuals staged according to different grades of intestinal metaplasia. Results: Six antigens, including CTAG1B/CTAG2, DDX53, IGF2BP2, TP53, and MAGEA3, were predominantly…

Lack of association between miR-27a, miR-146a, miR-196a-2, miR-492 and miR-608 gene polymorphisms and colorectal cancer

Colorectal cancer (CRC) is one of the most common cancers worldwide with high mortality rates. MicroRNAs (miRNAs) have an established role in the development of different cancers. Single nucleotide polymorphisms (SNPs) in miRNA related genes were linked with various gastrointestinal malignancies. However, the data on association between miRNA SNPs and CRC development are inconsistent. The aim of the present study was to evaluate the association between miRNA-related gene polymorphisms (miR-27a, miR-146a, miR-196a-2, miR-492 and miR-608) and the presence of CRC in European population. Gene polymorphisms were analyzed in 621 subjects (controls: n = 428; CRC: n = 193). MiR-27a T>C (rs895819), …