This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ohmiya, N. Articles by Goto, H. Search for Related Content PubMed PubMed Citation Articles by Ohmiya, N. Articles by Goto, H.

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

Naoki Ohmiya, Ayumu Taguchi, Nobuyuki Mabuchi, Akihiro Itoh, Yoshiki Hirooka, Yasumasa Niwa, Hidemi Goto

From the Department of Gastroenterology, Nagoya University Graduate School of Medicine; and the Department of Endoscopy, Nagoya University Hospital, Nagoya, Japan

Address reprint requests to Naoki Ohmiya, MD, PhD, Department of Gastroenterology, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, Japan 466-8550; e-mail: nohmiya{at}med.nagoya-u.ac.jp

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.

Presented in poster format at the American Gastroenterological Association (DDW 2006), Los Angeles, CA, May 24, 2006.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

This article has been cited by other articles:

				A. Woelfelschneider, O. Popanda, C. Lilla, J. Linseisen, C. Mayer, O. Celebi, J. Debus, H. Bartsch, J. Chang-Claude, and P. Schmezer A distinct ERCC1 haplotype is associated with mRNA expression levels in prostate cancer patients Carcinogenesis, September 1, 2008; 29(9): 1758 - 1764. [Abstract] [Full Text] [PDF]

				K. Asomaning, A. E. Reid, W. Zhou, R. S. Heist, R. Zhai, L. Su, E. L. Kwak, L. Blaszkowsky, A. X. Zhu, D. P. Ryan, et al. MDM2 Promoter Polymorphism and Pancreatic Cancer Risk and Prognosis Clin. Cancer Res., June 15, 2008; 14(12): 4010 - 4015. [Abstract] [Full Text] [PDF]

				Y. J. Yoon, H. Y. Chang, S. H. Ahn, J. K. Kim, Y. K. Park, D. R. Kang, J. Y. Park, S. M. Myoung, D. Y. Kim, C. Y. Chon, et al. MDM2 and p53 polymorphisms are associated with the development of hepatocellular carcinoma in patients with chronic hepatitis B virus infection Carcinogenesis, June 1, 2008; 29(6): 1192 - 1196. [Abstract] [Full Text] [PDF]

				S. Cattelani, R. Defferrari, S. Marsilio, R. Bussolari, O. Candini, F. Corradini, G. Ferrari-Amorotti, C. Guerzoni, L. Pecorari, C. Menin, et al. Impact of a Single Nucleotide Polymorphism in the MDM2 Gene on Neuroblastoma Development and Aggressiveness: Results of a Pilot Study on 239 Patients Clin. Cancer Res., June 1, 2008; 14(11): 3248 - 3253. [Abstract] [Full Text] [PDF]

				I. Gryshchenko, S. Hofbauer, M. Stoecher, P. T. Daniel, M. Steurer, A. Gaiger, K. Eigenberger, R. Greil, and I. Tinhofer MDM2 SNP309 Is Associated With Poor Outcome in B-Cell Chronic Lymphocytic Leukemia J. Clin. Oncol., May 10, 2008; 26(14): 2252 - 2257. [Abstract] [Full Text] [PDF]

				S. S. Lum, H. W. Chua, H. Li, W.-F. Li, N. Rao, J. Wei, Z. Shao, and K. Sabapathy MDM2 SNP309 G allele increases risk but the T allele is associated with earlier onset age of sporadic breast cancers in the Chinese population Carcinogenesis, April 1, 2008; 29(4): 754 - 761. [Abstract] [Full Text] [PDF]

				P. A. Bradbury, R. S. Heist, M. H. Kulke, W. Zhou, A. L. Marshall, D. P. Miller, L. Su, S. Park, J. Temel, P. Fidias, et al. A Rapid Outcomes Ascertainment System Improves the Quality of Prognostic and Pharmacogenetic Outcomes from Observational Studies Cancer Epidemiol. Biomarkers Prev., January 1, 2008; 17(1): 204 - 211. [Abstract] [Full Text] [PDF]

				Z. Hu, G. Jin, L. Wang, F. Chen, X. Wang, and H. Shen MDM2 Promoter Polymorphism SNP309 Contributes to Tumor Susceptibility: Evidence from 21 Case-Control Studies Cancer Epidemiol. Biomarkers Prev., December 1, 2007; 16(12): 2717 - 2723. [Abstract] [Full Text] [PDF]

				S. Wilkening, J. L. Bermejo, and K. Hemminki MDM2 SNP309 and cancer risk: a combined analysis Carcinogenesis, November 1, 2007; 28(11): 2262 - 2267. [Abstract] [Full Text] [PDF]

				M. K. Schmidt, S. Reincke, A. Broeks, L. M. Braaf, F. B.L. Hogervorst, R. A.E.M. Tollenaar, N. Johnson, O. Fletcher, J. Peto, J. Tommiska, et al. Do MDM2 SNP309 and TP53 R72P Interact in Breast Cancer Susceptibility? A Large Pooled Series from the Breast Cancer Association Consortium Cancer Res., October 1, 2007; 67(19): 9584 - 9590. [Abstract] [Full Text] [PDF]

				P. Rajaraman, S. S. Wang, N. Rothman, M. M. Brown, P. M. Black, H. A. Fine, J. S. Loeffler, R. G. Selker, W. R. Shapiro, S. J. Chanock, et al. Polymorphisms in Apoptosis and Cell Cycle Control Genes and Risk of Brain Tumors in Adults Cancer Epidemiol. Biomarkers Prev., August 1, 2007; 16(8): 1655 - 1661. [Abstract] [Full Text] [PDF]

				R. S. Heist, W. Zhou, L. R. Chirieac, T. Cogan-Drew, G. Liu, L. Su, D. Neuberg, T. J. Lynch, J. C. Wain, and D. C. Christiani MDM2 Polymorphism, Survival, and Histology in Early-Stage Non-Small-Cell Lung Cancer J. Clin. Oncol., June 1, 2007; 25(16): 2243 - 2247. [Abstract] [Full Text] [PDF]

				M. Sanchez-Carbayo, N. D. Socci, T. Kirchoff, N. Erill, K. Offit, B. H. Bochner, and C. Cordon-Cardo A Polymorphism in HDM2 (SNP309) Associates with Early Onset in Superficial Tumors, TP53 Mutations, and Poor Outcome in Invasive Bladder Cancer Clin. Cancer Res., June 1, 2007; 13(11): 3215 - 3220. [Abstract] [Full Text] [PDF]