ArticleGastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association2018
Clinical and biological significance of a - 73A > C variation in the CDH1 promoter of patients with sporadic gastric carcinoma.
Article in Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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4 citing papers in PubMed, 6 citations in OpenAlex.
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- Promotion of rs3746804 (p. L267P) polymorphism to intracellular SLC52A3a trafficking and riboflavin transportation in esophageal cancer cells.Amino acids · 2021Article
- DNA Methylation and SNPs in VCX are Correlated with Sex Differences in the Response to Chronic Hepatitis B.Virologica Sinica · 2019Article
- CDH1 somatic alterations in Mexican patients with diffuse and mixed sporadic gastric cancer.BMC cancer · 2019Article
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7 authors at 2 institutions in 3 countries.
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Abstract
backgroundCDH1 germline mutations lead to hereditary diffuse gastric carcinomas. However, it is unclear whether genetic variations in the CDH1 promoter affect the progression of sporadic gastric carcinomas (SGCs).
methodsSGC patients in two independent cohorts with follow-up data were enrolled. The CDH1 genotypes, including the - 73A > C polymorphism (rs28372783), were determined by PCR sequencing. The CDH1 promoter activity was determined using reporter assays. SNAIL bound to CDH1 alleles was determined by chromatin immunoprecipitation primer extension PCR. CDH1 DNA methylation was determined by bisulfite-based PCR analyses.
resultsKaplan-Meier analyses showed that the overall survival (OS) of the - 73C/C patients was significantly longer than that of the - 73A/C or - 73A/A patients in a Chinese cohort [n = 526; hazard ratio 0.68 (95% CI 0.47-1.00)], which was validated in an independent Korea cohort [n = 215; hazard ratio 0.49 (95% CI 0.26-0.94)]. Moreover, the transcription activity of the - 73C alleles was significantly higher than that of the - 73A alleles in vitro and in vivo. The ratio of SNAIL recruited to the promoter regions of the - 73C and - 73A alleles was 1:10, indicating a strong influence of this polymorphism on the recruitment of SNAIL to the flanking E-box. The prevalence of DNA methylation of the CpG island and shore within the promoter of the - 73C allele was much less than that of the - 73A allele in both gastric tissues and cancer cell lines.
conclusionThe - 73A > C variation may lead to differences in the overall survival of SGC patients and allele-specific repressions of CDH1.
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