H. pylori Infection Is a Key Risk Factor for Proximal Gastric Cancer

Bornschein, Jan; Selgrad, Michael; Warnecke, Maren; Kuester, Doerthe; Wex, Thomas; Malfertheiner, Peter

doi:10.1007/s10620-010-1351-x

Cited by 88 publications

(65 citation statements)

References 53 publications

(59 reference statements)

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“…We could demonstrate that the prevalence of H. pylori infection was similar in patients with proximal and distal GC [28]. There is also a role for H. pylori-driven carcinogenesis in GC at the esophagogastric junction when correct allocation of the main tumor mass is applied, and AEG I and Barrett carcinomas are strictly excluded from the analysis.…”

Section: H Pylori As High Risk Indicatormentioning

confidence: 75%

Gastric Cancer: Clinical Aspects, Epidemiology and Molecular Background

et al. 2011

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In 2010, the WHO introduced the seventh edition of the tumor node metastasis (TNM) classification that provides a more detailed classification for both local tumor invasion (T) and lymph node involvement (N) compared with the previous version. The T and N categories of tumors located in the stomach have been further modified with the intention to ensure a better correlation to the prognostic outcome. For the classification of a pN0, the number of lymph nodes has been adjusted to 16.The description of tumors with origin in the esophagus has been simplified and includes tumors of the esophagogastric junction as well as gastric tumors extending to the proximal 5 cm of the stomach. Major changes are further the subclassification of the categories T1 and T4 and the new N categorization now considering the number of lymph nodes involved within tree categories. Furthermore, positive lymph nodes in the region of the celiac trunc are considered as regional in case of esophageal cancers.The validity of the new classification system in its prognostic efficacy was compared to the previous edition. A study conducted in China proved a better prognostic stratification for the new actualized version [1]. Another study from Korea showed similar results for the new TNM system, proving a more detailed prognostic assessment, especially between T2 and T3 and N1 and N2 tumors [2]. The advantage of the new (7th) edition was mainly confirmed for the prognostic value of accurate lymph node assessment [3].Concerning the classification of early gastric cancer (GC) in the new system, a study from Italy confirmed the usefulness of the new classification for metastatic lymph nodes as a prognostic tool in case of early GC. AbstractThe validity and usefulness of the 7th edition of the UICC tumor node metastasis classification in the context of clinical management of gastric cancer are discussed. The most relevant new agent in gastric cancer therapy is trastuzumab for HER2-positive gastric carcinomas. This marks the success of continuous effort of translational research. Trastuzumab, initially applied in palliative settings, is currently being evaluated also in neoadjuvant treatment regimens. Several new meta-analyses support the carcinogenic effect of high salt intake and smoking in the context of Helicobacter pylori infection. Further data have become available on the efficacy of protective agents, acetyl salicylic acid ⁄ nonsteroidal anti-inflammatory drugs, and antioxidants. In search for a successful prevention strategy, the focus is on the identification of individuals at high risk who demand screening (testing) and surveillance. Serological assessment of gastric mucosal abnormalities with increased risk for gastric cancer development is extensively studied, and new data are presented from Asia as well as from Europe. New high-throughput techniques combined with bioinformatic vector analysis open the gate to the identification of new potential diagnostic and therapeutic targets. Furthermore, these approaches allow us to elucidate the int...

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Section: H Pylori As High Risk Indicatormentioning

confidence: 75%

Gastric Cancer: Clinical Aspects, Epidemiology and Molecular Background

et al. 2011

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“…82 Up to 25% of human cancers are considered inflammation-related, 83 gastroenterological organs in particular have a notably strong association, viz. colon cancer and inflammatory bowel disease, 84 chronic Helicobacter pylori gastritis and gastric cancer, 85 hepatitis B & C and liver cancer 86 and reflux esophagitis/BE and EAC. 87 Inflammation can act as a classical tumor promoter, increasing the risk and tumor progression.…”

Section: Reflux Disease Barrett's Esophagus (Be) and Esophageal Adenmentioning

confidence: 99%

Targeting chemokine pathways in esophageal adenocarcinoma

et al. 2014

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y These authors Contributed equally to this work. E sophageal adenocarcinoma (EAC) is one of the fastest growing malignancies in the US and needs newer therapeutic and diagnostic strategies. Chronic inflammation plays a role in the pathogenesis of EAC and contributes to the dysplastic conversion of normal esophageal epithelium to Barrett's esophagus and frank adenocarcinoma. Chemokines play important roles in mediating inflammation and recent evidence implicates these ligands and their receptors in the development and spread of various tumors. We demonstrated that the chemokines IL8, CXCL1 and CXCL3 are significantly overexpressed during esophageal carcinogenesis and accompanied by amplification and demethylation of the chr4q21 gene locus. We also demonstrated that IL8 levels can be detected in serum of patients with EAC and can serve as potential biomarkers. We now demonstrate that inhibition of IL8 receptor, CXCR2, leads to decreased invasiveness of esophageal adenocarcinoma derived cells without affecting cellular proliferation. Taken together, these studies reveal the important roles that chemokines play in development of esophageal cancer and demonstrate that these pathways can serve as potential therapeutic targets.

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“…While early studies claim that H. pylori infection is only related to distal or ‘non-cardia' gastric cancer, this is no longer true since there is clear evidence now for the pathogenetic relevance also in proximal gastric cancer or adenocarcinomas at the esophagogastric junction, if proper allocation of the tumor and assessment of the relevant risk factor are performed [15,16,17]. The risk for gastric carcinogenesis by H. pylori infection is similar for intestinal- and diffuse-type gastric cancers [15,18].…”

Section: Helicobacter Pylori - Epidemiological Backgroundmentioning

confidence: 99%

Helicobacter pylori and Gastric Cancer

Bornschein

Malfertheiner

2014

Dig Dis

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Infection with Helicobacter pylori is established as the major risk factor for gastric cancer development. Damage of the mucosal barrier due to H. pylori-induced inflammation enhances the carcinogenic effect of other risk factors such as salt intake or tobacco smoking. The genetic disposition of both the bacterial strain and the host can increase the potential towards gastric cancer formation. Genetic variance of the bacterial proteins CagA and VacA is associated with a higher gastric cancer risk, as are polymorphisms and epigenetic changes in host gene coding for interleukins (IL1β, IL8), transcription factors (CDX2, RUNX3) and DNA repair enzymes. Application of high-throughput assays for genome-wide assessment of either genetic structural variance or gene expression patterns may lead to a better understanding of the pathobiological background of these processes, including the underlying signaling pathways. Understanding of the stepwise alterations that take place in the transition from chronic atrophic gastritis, via metaplastic changes, to invasive neoplasia is vital to define the ‘point of no return' before which eradication of H. pylori has the potential to prevent gastric cancer. Currently, eradication as preventive strategy is only recommended for high-incidence regions in Asia; large population studies with an adequate follow-up are required to demonstrate the effectiveness of such an approach in Western populations.

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H. pylori Infection Is a Key Risk Factor for Proximal Gastric Cancer

Cited by 88 publications

References 53 publications

Gastric Cancer: Clinical Aspects, Epidemiology and Molecular Background

Gastric Cancer: Clinical Aspects, Epidemiology and Molecular Background

Targeting chemokine pathways in esophageal adenocarcinoma

Helicobacter pylori and Gastric Cancer

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