DOI: 10.1200/jco.2005.04.1459. <i>MDM2</i> Promoter Polymorphism Is Associated With Both an Increased Susceptibility to Gastric Carcinoma and Poor Prognosis

MDM2 Promoter Polymorphism Is Associated With Both an Increased Susceptibility to Gastric Carcinoma and Poor Prognosis

10.1200/jco.2005.04.1459

Crossref journal-article

American Society of Clinical Oncology (ASCO)

Journal of Clinical Oncology (233)

Abstract

Purpose Recently, a single-nucleotide polymorphism in the MDM2 promoter (SNP309) has been found to lower the age of onset of tumors and increase the occurrence of multiple primary tumors in Li-Fraumeni syndrome, and accelerate the development of sporadic adult soft tissue sarcoma. The aim of this study was to determine whether SNP309 is associated with susceptibility to gastric carcinoma and its prognosis. Patients and Methods In a case-control study including 438 controls and 410 patients with sporadic gastric carcinoma, MDM2 SNP309 was genotyped. Serum pepsinogens (PGs) I and II were measured in 438 control subjects and 253 cases selected from 410 patients. Tumor tissue was immunostained with p53 and examined for mutations in exons 5 to 8 of p53 using polymerase chain reaction–based single strand conformational polymorphism analysis and direct sequencing. Results The risk of overall gastric carcinoma for SNP309 (G/G) was significantly increased when compared with T carriers (P = .039), especially carcinomas with extragastric tumors (P = .005), carcinoma with severe atrophic gastritis positive for PG assay (PG I level < 70 ng/mL and PG I/II < 3.0; P = .005), antral carcinoma (P = .020), intestinal-type carcinoma (P = .023), p53-immunopositive carcinoma (P = .007), and carcinoma with p53 mutations (P = .007). No significant difference in age at diagnosis was observed among genotypes. SNP309 (G/G) was an independent marker of poor overall survival in advanced carcinoma (hazard ratio, 3.16; 95% CI, 1.22 to 8.20; P = .018). Conclusion This study provides evidence supporting the association of SNP309 with gastric carcinogenesis via p53 tumor suppressor pathway, extragastric tumorigenesis, and poor prognosis.

Bibliography

Ohmiya, N., Taguchi, A., Mabuchi, N., Itoh, A., Hirooka, Y., Niwa, Y., & Goto, H. (2006). MDM2 Promoter Polymorphism Is Associated With Both an Increased Susceptibility to Gastric Carcinoma and Poor Prognosis. Journal of Clinical Oncology, 24(27), 4434â4440.

Authors 7

Naoki Ohmiya (first)
Ayumu Taguchi (additional)
Nobuyuki Mabuchi (additional)
Akihiro Itoh (additional)
Yoshiki Hirooka (additional)
Yasumasa Niwa (additional)
Hidemi Goto (additional)

References 46 Referenced 107

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10.1016/j.cell.2004.11.022
Schneider-Stock R, Radig K, Oda Y, et al: p53 gene mutations in soft-tissue sarcomas: Correlations with p53 immunohistochemistry and DNA ploidy. J Cancer Res Clin Oncol 123:211,1997-218, (10.1007/BF01240317)
Cordon-Cardo C, Latres E, Drobnjak M, et al: Molecular abnormalities of mdm2 and p53 genes in adult soft tissue sarcomas. Cancer Res 54:794,1994-799,
Renault B, van den Broek M, Fodde R, et al: Base transitions are the most frequent genetic changes at P53 in gastric cancer. Cancer Res 53:2614,1993-2617,
10.1073/pnas.89.7.3030
10.1126/science.1948068
Sugimura T, Kawachi T: Experimental stomach cancer. Methods Cancer Res 7:245,1973-308,
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Dates

Type	When
Created	18 years, 11 months ago (Sept. 18, 2006, 6:31 p.m.)
Deposited	3 years, 2 months ago (May 25, 2022, 5:22 p.m.)
Indexed	11 months ago (Sept. 20, 2024, 11:44 a.m.)
Issued	18 years, 11 months ago (Sept. 20, 2006)
Published	18 years, 11 months ago (Sept. 20, 2006)
Published Print	18 years, 11 months ago (Sept. 20, 2006)

Funders 0

None

BibTeX

@article{Ohmiya_2006, title={MDM2 Promoter Polymorphism Is Associated With Both an Increased Susceptibility to Gastric Carcinoma and Poor Prognosis}, volume={24}, ISSN={1527-7755}, url={http://dx.doi.org/10.1200/jco.2005.04.1459}, DOI={10.1200/jco.2005.04.1459}, number={27}, journal={Journal of Clinical Oncology}, publisher={American Society of Clinical Oncology (ASCO)}, author={Ohmiya, Naoki and Taguchi, Ayumu and Mabuchi, Nobuyuki and Itoh, Akihiro and Hirooka, Yoshiki and Niwa, Yasumasa and Goto, Hidemi}, year={2006}, month=sep, pages={4434–4440} }

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