Differences in proximal (cardia) versus distal (antral) gastric carcinogenesis via retinoblastoma pathway

Gulmann, Christian; Hegarty, Helen; Grace, Antoinette; Leader, M.; Patchett, Stephen; Kay, Elaine W.

doi:10.3748/wjg.v10.i1.17

Cited by 16 publications

(14 citation statements)

References 21 publications

(20 reference statements)

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“…Different polymorphisms in gastric adenocarcinomas of different locations strongly support the hypothesis that the tumours of those two locations are genetically different, which may account for some of the observed epidemiological differences between cardia and non-cardia cancers [51]. These findings may be a reflection of differences in the interaction between WRN codon 1367 polymorphisms and local factors in the stomach.…”

Section: Discussionmentioning

confidence: 81%

Polymorphisms of the TP53 codon 72 and WRN codon 1367 in individuals from Northern Brazil with gastric adenocarcinoma

et al. 2005

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Gastric cancer is the second most frequent type of neoplasia and also the second most common cause of death in the world. TP53 codon 72, which produces variant proteins with an arginine (Arg) or proline (Pro), has been reported to be associated with cancers of the lung, oesophagus, stomach and cervix. Werner's syndrome (WS) is a premature ageing disease caused by a mutation in the WRN gene. The WRN protein acts as a DNA helicase and as an exonuclease. WRN codon 1367 produces variant proteins with an Arg or cysteine (Cys). This polymorphism has been studied, in order to understand the clinical impact of the molecular variants in WS and in age-related disorders. In the present study, the TP53 codon 72 and the WRN codon 1367 polymorphisms were investigated in 54 gastric adenocarcinoma patients (31 diffuse-type and 25 intestinal-type) and 54 controls. DNA samples were extracted, and PCR-RFLP was utilised for genotyping TP53 codon 72 and WRN codon 1367. The allele frequencies of the TP53 polymorphism were: Arg=0.74 and Pro=0.26. The allele frequencies of the WRN polymorphism were: Cys=0.73 and Arg=0.27. The crude genotypic frequencies in gastric cancer patients were similar to those of the controls, but in the WRN codon 1367 polymorphisms the mean age tended to be higher in the Arg/Arg genotypes. There also was an association, although not statistically significant, between the presence of Helicobacter pylori and the genotypes Cys/Cys and Cys/Arg and a higher percentage of cardia cancer among the Arg/Arg genotypes, and of non-cardia cancer among genotypes Cys/Cys and Cys/Arg. These findings may be a reflection of differences in the interaction between WRN codon 1367 polymorphisms and local factors in the stomach. To our knowledge, this is the first study to examine a genetic polymorphism of the WRN gene in cancer. The precise mechanisms of action of the TP53 and WRN polymorphisms involved in the aetiopathogeny of this disease need further investigation.

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Section: Discussionmentioning

confidence: 81%

Polymorphisms of the TP53 codon 72 and WRN codon 1367 in individuals from Northern Brazil with gastric adenocarcinoma

et al. 2005

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“…In addition, multiple environmental factors, including Helicobacter pylori infection and dietary factors, have been implicated in the initiation of gastric carcinogenesis 21, 22. Among the different kinds of gastric carcinoma, cardia carcinoma may form a specialized subtype that differs from carcinomas of other parts of the stomach according to recent studies of the clinicopathologic characteristics and alterations of carcinoma‐associated genes 11–15, 23–26. The main objective of the current study was to demonstrate the characteristics of cardia carcinoma by investigating the detailed clinicopathologic features and alterations in protein expression associated with this type of gastric carcinoma.…”

Section: Discussionmentioning

confidence: 99%

Clinicopathologic and protein expression differences between cardia carcinoma and noncardia carcinoma of the stomach

Kim

Lee

Yang

et al. 2005

Cancer

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BACKGROUNDAlthough the incidence of adenocarcinoma of the stomach has decreased over the past several decades, gastric cardia carcinoma has increased over the same period.METHODSThe clinicopathologic characteristics and immunohistochemical staining results of 21 proteins were investigated in 165 patients with cardia carcinoma, including 74 patients with true cardia carcinoma and 91 patients with subcardia carcinoma, and the results were compared with the results from 564 patients with noncardia carcinoma.RESULTSIn the clinicopathologic analysis, patients who had cardia carcinoma tended to have tumors with poorly differentiated histology according to the World Health Organization classification system (P = 0.012), diffuse type according to the Lauren classification system (P = 0.049), and advanced pathologic TNM stage (P < 0.001). On immunohistochemical staining, loss of the p16 (P = 0.038) and smad4 (P < 0.001) tumor suppressor genes was more frequent in cardia carcinoma than in noncardia carcinoma. Carcinoembryonic antigen and CD44 overexpression were more frequent in patients with cardia carcinoma (P < 0.05). Conversely, patients who had cardia carcinoma exhibited less frequent expression of MUC1 (P = 0.008) and MUC5AC (P = 0.006) compared with patients who had noncardia carcinoma. Epstein–Barr virus infection was more common in patients with cardia carcinoma (P < 0.001). In the survival analysis, the patients with cardia carcinoma had a poorer prognosis. In the multivariate analysis, tumor location in the cardia was confirmed as an independent, poor prognostic factor in patients with gastric carcinoma.CONCLUSIONCardia carcinoma and noncardia carcinoma differed in their clinicopathologic characteristics and in their alterations of gene expression, as evaluated by immunohistochemistry. The current results support the hypothesis that cardia carcinoma forms a specific category of gastric carcinoma that is distinct from noncardia carcinoma. Cancer 2005. © 2005 American Cancer Society.

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“…Clinical presentation of proximal gastric cancer is advanced in most patients due to its unique anatomical location. Because of the associated high incidence of lymph node metastasis 15 and poor biological behavior 16, the diagnosis of the proximal gastric cancer is most often at advanced stage and it recurs in relatively higher incidence after radical resection 17. As a result, the prognosis of proximal gastric cancer patients is worse than that of patients with gastric cancer located at the middle or distal third of the stomach 3.…”

Section: Introductionmentioning

confidence: 99%

The pattern and risk factors of recurrence of proximal gastric cancer after curative resection

Zhang

Liang

et al. 2012

Journal of Surgical Oncology

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Differences in proximal (cardia) versus distal (antral) gastric carcinogenesis via retinoblastoma pathway

Cited by 16 publications

References 21 publications

Polymorphisms of the TP53 codon 72 and WRN codon 1367 in individuals from Northern Brazil with gastric adenocarcinoma

Polymorphisms of the TP53 codon 72 and WRN codon 1367 in individuals from Northern Brazil with gastric adenocarcinoma

Clinicopathologic and protein expression differences between cardia carcinoma and noncardia carcinoma of the stomach

The pattern and risk factors of recurrence of proximal gastric cancer after curative resection

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