DBGC: A Database of Human Gastric Cancer

Wang, Chao; Zhang, Jun; Mingdeng, Cai; Zhu, Zhenggang; Gu, Wenjie; Yu, Yingyan; Zhang, Xiaoyan

doi:10.1371/journal.pone.0142591

Cited by 30 publications

(29 citation statements)

References 27 publications

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“…Gastric cancer has the third highest mortality and fourth highest morbidity rates of all cancers worldwide (1). In 2012, GloboCan statistics reported almost 1 million new cases of gastric cancer, and more than 700,000 mortalities caused by gastric cancer (1).…”

Section: Introductionmentioning

confidence: 99%

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Association of P53 gene polymorphism with gastric cancer in Northern Iran as a high‑risk region

et al. 2018

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Abstract. Gastric cancer has the fourth highest morbidity rate of all cancers worldwide. Genetic factors including alterations in oncogenes and tumor suppressor genes serve an important role in gastric cancer development and progression. The P53 gene acts as a tumor suppressor gene by regulating the cell cycle, DNA transcription and repair, apoptosis, senescence and genome stability. In addition to somatic P53 mutations in cancer development, germline polymorphisms are also involved in different malignancies. The polymorphism of P53 at codon 72 (Arg72Pro) is established as a common variant that increases susceptibility to various cancers. The present case-control study was conducted to evaluate the possible association between this P53 polymorphism and gastric cancer in the Iranian population. A total of 59 patients with gastric cancer and 59 healthy controls were enrolled in the present study. Genomic DNA was extracted from peripheral blood mononuclear cells and genotype analysis was performed using a polymerase chain reaction-based restriction fragment length polymorphism assay. Genotype frequencies did not differ significantly between the patients and controls (P=0.4); the frequencies of the three genotypes Arg/Arg, Arg/Pro and Pro/Pro in gastric cancer patients were 28.8, 49.2 and 22.0%, and in controls were 37.3, 49.2 and 13.6%. Additionally, there were no differences in genotype frequencies based on tumor location, histological differentiation or tumor stage. Based on these findings, it may be concluded that the P53 codon 72 polymorphism does not contribute to gastric cancer susceptibility in Northern Iran. IntroductionGastric cancer has the third highest mortality and fourth highest morbidity rates of all cancers worldwide (1). In 2012, GloboCan statistics reported almost 1 million new cases of gastric cancer, and more than 700,000 mortalities caused by gastric cancer (1). Gastric cancer is a multifactorial disorder, in which genetic and environmental interactions serve an important role in development and progression (2). Increasing age, gender, lifestyle, dietary regime, environmental factors and Helicobacter pylori infections are among the known risk factors for stomach cancer (3,4). While dietary regime and lifestyle are the most recognized factors, more effective identification of the genetic risk factors is expected to improve understanding of the basic molecular events involved in tumorigenesis (5). Various genetic and epigenetic changes that have the potential to convert normal epithelial cells in the stomach into malignant neoplasms may be responsible for the development of both familial and sporadic gastric cancer (6,7). Studies performed recently have demonstrated that a high number of genes and various environmental factors are the causal agents of gastric cancer, and the presence of different forms of alleles in genes (polymorphisms) may promote the development of cancers; in this regard, the P53 gene has been a research focus due to its role as a major tumor suppressor gene (8,9). The P53 ge...

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Section: Introductionmentioning

confidence: 99%

“…In 2012, GloboCan statistics reported almost 1 million new cases of gastric cancer, and more than 700,000 mortalities caused by gastric cancer (1). Gastric cancer is a multifactorial disorder, in which genetic and environmental interactions serve an important role in development and progression (2).…”

Section: Introductionmentioning

confidence: 99%

Association of P53 gene polymorphism with gastric cancer in Northern Iran as a high‑risk region

et al. 2018

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“…Gastric cancer (GC) is the third most common cause of cancer-related deaths worldwide (1). Chemotherapy is the standard of care for the majority of patients with advanced, unresectable or metastatic disease (2) with standard firstline treatment being fluoropyrimidine plus platinum combinations (3); patients who have human epidermal growth factor 2 (HER2)-positive tumours should also receive trastuzumab.…”

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confidence: 99%

A Phase I Study of Napabucasin Plus Paclitaxel for Japanese Patients With Advanced/Recurrent Gastric Cancer

Shitara¹,

Yodo²,

Iino³

2019

In Vivo

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Aim: To report results from the first phase I study of napabucasin plus paclitaxel in Japanese patients with pretreated unresectable/recurrent gastric cancer. Patients and Methods: Patients received napabucasin (480 mg bid) plus paclitaxel [80 mg/m 2 on days 3, 10 and 17 (cycles 1 and 2) and on days 1, 8 and 15 (cycle 3 and subsequent cycles)] until disease progression or unacceptable toxicity. Primary objectives were tolerability, safety and pharmacokinetics of napabucasin plus paclitaxel. Trial registration ID: JapicCTI-142420. Results: Six patients were enrolled. Paclitaxel had a minimal effect on napabucasin pharmacokinetics and median plasma paclitaxel concentrations were similar in combination and monotherapy. No dose-limiting toxicities were observed. There were no grade 4/5 adverse events. Partial response, stable disease and progressive disease were reported in two patients each. Conclusion: Napabucasin plus paclitaxel was well-tolerated in Japanese patients with gastric cancer.

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“…However, lack of properly validated benchmarking represents the main limiting factor hampering wider application in a clinical scenario (Walsh, Pollastri, & Tosatto, ). Variants affecting tumor‐suppressor genes, such as TP53 (Liu & Bodmer, ), VHL (Leonardi, Martella, Tosatto, & Murgia, ), and CDKN2A (Scaini et al., ) are actively investigated and collected in freely accessible databases (Forbes et al., ; Tabaro et al., ; Wang et al., ). However, the correct interpretation of their pathogenic significance is far from definitively addressed.…”

Section: Introductionmentioning

confidence: 99%

Performance of in silico tools for the evaluation of p16INK4a (CDKN2A) variants in CAGI

et al. 2017

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Correct phenotypic interpretation of variants of unknown significance for cancer-associated genes is a diagnostic challenge as genetic screenings gain in popularity in the next-generation sequencing era. The Critical Assessment of Genome Interpretation (CAGI) experiment aims to test and define the state of the art of genotype-phenotype interpretation. Here, we present the assessment of the CAGI p16INK4a challenge. Participants were asked to predict the effect on cellular proliferation of ten variants for the p16INK4a tumor suppressor, a cyclin-dependent kinase inhibitor encoded by the CDKN2A gene. Twenty-two pathogenicity predictors were assessed with a variety of accuracy measures for reliability in a medical context. Different assessment measures were combined in an overall ranking to provide more robust results. The R scripts used for assessment are publicly available from a GitHub repository for future use in similar assessment exercises. Despite a limited test-set size, our findings show a variety of results, with some methods performing significantly better. Methods combining different strategies frequently outperform simpler approaches. The best predictor, Yang&Zhou lab, uses a machine learning method combining an empirical energy function measuring protein stability with an evolutionary conservation term. The p16INK4a challenge highlights how subtle structural effects can neutralize otherwise deleterious variants.

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DBGC: A Database of Human Gastric Cancer

Cited by 30 publications

References 27 publications

Association of P53 gene polymorphism with gastric cancer in Northern Iran as a high‑risk region

Association of P53 gene polymorphism with gastric cancer in Northern Iran as a high‑risk region

A Phase I Study of Napabucasin Plus Paclitaxel for Japanese Patients With Advanced/Recurrent Gastric Cancer

Performance of in silico tools for the evaluation of p16INK4a (CDKN2A) variants in CAGI

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