p53, p21, and p73 gene polymorphisms in gastric carcinoma

Osamu Shirai, Naoki Ohmiya, Ayumu Taguchi, Masanao Nakamura, Hiroki Kawashima, Ryoji Miyahara, Akihiro Itoh, Yoshiki Hirooka, Osamu Watanabe, Takafumi Ando, Yasuyuki Goto, Nobuyuki Hamajima, Hidemi Goto

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Background/Aims: The aim of this study was to evaluate the association of genetic polymorphisms of p53, p21, and p73 genes with susceptibility to gastric carcinoma (GC), its clinicopathologic features, and prognosis. Methodology: In a case-control study including 419 controls and 389 patients with sporadic GC, single nucleotide polymorphisms (SNPs) of p53 Arg72Pro, p21 Ser31Arg, andp73 G4C14-to-A4T14 at exon 2 were genotyped. Tumor tissue was immunostained with p53 and examined for mutations in exons 5 to 8 of p53 using PCR -based single strand conformational polymorphism analysis and direct sequencing. Results: The SNPs of p53, p21, and p73 genes were not significantly associated with susceptibility to GC. p53 SNP (Pro/Pro) was significantly associated with increased risks for the following subgroups: invasive infiltration-type carcinoma (odds ratio [OR], 2.09; 95%CI, 1.01 to 4.34; p=0.048), carcinoma with peritoneal dissemination (OR, 3.42; 95%CI, 1.05 to 11.08; p=0.04), and carcinoma with distant metastasis (OR, 3.90; 95%CI, 1.14 to 13.38; p=0.03), but not with p53 immunoreactivity or mutations when compared with wild type. With respect to prognosis, p53 SNP (Pro/Pro) was an independent marker of poor overall survival in GC with TNM IB to IV stages (hazard ratio, 2.31; 95%CI, 1.14 to 4.69; p=0.02), especially in GC treated by chemotherapy (hazard ratio, 2.17; 95%CI, 1.06 to 4.41;p=0.03). Conclusions: This study provides evidence supporting the association of p53 SNP Arg72Pro with GC with invasive phenotype, peritoneal dissemination, distant metastasis, chemoresistance, and poor prognosis.

Original languageEnglish
Pages (from-to)1595-1601
Number of pages7
JournalHepato-gastroenterology
Volume57
Issue number104
Publication statusPublished - 01-11-2010
Externally publishedYes

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Stomach
Carcinoma
Single Nucleotide Polymorphism
Genes
Odds Ratio
Exons
Neoplasm Metastasis
Mutation
Genetic Polymorphisms
Case-Control Studies
Phenotype
Drug Therapy
Polymerase Chain Reaction
Survival
Neoplasms

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Gastroenterology

Cite this

Shirai, O., Ohmiya, N., Taguchi, A., Nakamura, M., Kawashima, H., Miyahara, R., ... Goto, H. (2010). p53, p21, and p73 gene polymorphisms in gastric carcinoma. Hepato-gastroenterology, 57(104), 1595-1601.
Shirai, Osamu ; Ohmiya, Naoki ; Taguchi, Ayumu ; Nakamura, Masanao ; Kawashima, Hiroki ; Miyahara, Ryoji ; Itoh, Akihiro ; Hirooka, Yoshiki ; Watanabe, Osamu ; Ando, Takafumi ; Goto, Yasuyuki ; Hamajima, Nobuyuki ; Goto, Hidemi. / p53, p21, and p73 gene polymorphisms in gastric carcinoma. In: Hepato-gastroenterology. 2010 ; Vol. 57, No. 104. pp. 1595-1601.
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abstract = "Background/Aims: The aim of this study was to evaluate the association of genetic polymorphisms of p53, p21, and p73 genes with susceptibility to gastric carcinoma (GC), its clinicopathologic features, and prognosis. Methodology: In a case-control study including 419 controls and 389 patients with sporadic GC, single nucleotide polymorphisms (SNPs) of p53 Arg72Pro, p21 Ser31Arg, andp73 G4C14-to-A4T14 at exon 2 were genotyped. Tumor tissue was immunostained with p53 and examined for mutations in exons 5 to 8 of p53 using PCR -based single strand conformational polymorphism analysis and direct sequencing. Results: The SNPs of p53, p21, and p73 genes were not significantly associated with susceptibility to GC. p53 SNP (Pro/Pro) was significantly associated with increased risks for the following subgroups: invasive infiltration-type carcinoma (odds ratio [OR], 2.09; 95{\%}CI, 1.01 to 4.34; p=0.048), carcinoma with peritoneal dissemination (OR, 3.42; 95{\%}CI, 1.05 to 11.08; p=0.04), and carcinoma with distant metastasis (OR, 3.90; 95{\%}CI, 1.14 to 13.38; p=0.03), but not with p53 immunoreactivity or mutations when compared with wild type. With respect to prognosis, p53 SNP (Pro/Pro) was an independent marker of poor overall survival in GC with TNM IB to IV stages (hazard ratio, 2.31; 95{\%}CI, 1.14 to 4.69; p=0.02), especially in GC treated by chemotherapy (hazard ratio, 2.17; 95{\%}CI, 1.06 to 4.41;p=0.03). Conclusions: This study provides evidence supporting the association of p53 SNP Arg72Pro with GC with invasive phenotype, peritoneal dissemination, distant metastasis, chemoresistance, and poor prognosis.",
author = "Osamu Shirai and Naoki Ohmiya and Ayumu Taguchi and Masanao Nakamura and Hiroki Kawashima and Ryoji Miyahara and Akihiro Itoh and Yoshiki Hirooka and Osamu Watanabe and Takafumi Ando and Yasuyuki Goto and Nobuyuki Hamajima and Hidemi Goto",
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Shirai, O, Ohmiya, N, Taguchi, A, Nakamura, M, Kawashima, H, Miyahara, R, Itoh, A, Hirooka, Y, Watanabe, O, Ando, T, Goto, Y, Hamajima, N & Goto, H 2010, 'p53, p21, and p73 gene polymorphisms in gastric carcinoma', Hepato-gastroenterology, vol. 57, no. 104, pp. 1595-1601.

p53, p21, and p73 gene polymorphisms in gastric carcinoma. / Shirai, Osamu; Ohmiya, Naoki; Taguchi, Ayumu; Nakamura, Masanao; Kawashima, Hiroki; Miyahara, Ryoji; Itoh, Akihiro; Hirooka, Yoshiki; Watanabe, Osamu; Ando, Takafumi; Goto, Yasuyuki; Hamajima, Nobuyuki; Goto, Hidemi.

In: Hepato-gastroenterology, Vol. 57, No. 104, 01.11.2010, p. 1595-1601.

Research output: Contribution to journalArticle

TY - JOUR

T1 - p53, p21, and p73 gene polymorphisms in gastric carcinoma

AU - Shirai, Osamu

AU - Ohmiya, Naoki

AU - Taguchi, Ayumu

AU - Nakamura, Masanao

AU - Kawashima, Hiroki

AU - Miyahara, Ryoji

AU - Itoh, Akihiro

AU - Hirooka, Yoshiki

AU - Watanabe, Osamu

AU - Ando, Takafumi

AU - Goto, Yasuyuki

AU - Hamajima, Nobuyuki

AU - Goto, Hidemi

PY - 2010/11/1

Y1 - 2010/11/1

N2 - Background/Aims: The aim of this study was to evaluate the association of genetic polymorphisms of p53, p21, and p73 genes with susceptibility to gastric carcinoma (GC), its clinicopathologic features, and prognosis. Methodology: In a case-control study including 419 controls and 389 patients with sporadic GC, single nucleotide polymorphisms (SNPs) of p53 Arg72Pro, p21 Ser31Arg, andp73 G4C14-to-A4T14 at exon 2 were genotyped. Tumor tissue was immunostained with p53 and examined for mutations in exons 5 to 8 of p53 using PCR -based single strand conformational polymorphism analysis and direct sequencing. Results: The SNPs of p53, p21, and p73 genes were not significantly associated with susceptibility to GC. p53 SNP (Pro/Pro) was significantly associated with increased risks for the following subgroups: invasive infiltration-type carcinoma (odds ratio [OR], 2.09; 95%CI, 1.01 to 4.34; p=0.048), carcinoma with peritoneal dissemination (OR, 3.42; 95%CI, 1.05 to 11.08; p=0.04), and carcinoma with distant metastasis (OR, 3.90; 95%CI, 1.14 to 13.38; p=0.03), but not with p53 immunoreactivity or mutations when compared with wild type. With respect to prognosis, p53 SNP (Pro/Pro) was an independent marker of poor overall survival in GC with TNM IB to IV stages (hazard ratio, 2.31; 95%CI, 1.14 to 4.69; p=0.02), especially in GC treated by chemotherapy (hazard ratio, 2.17; 95%CI, 1.06 to 4.41;p=0.03). Conclusions: This study provides evidence supporting the association of p53 SNP Arg72Pro with GC with invasive phenotype, peritoneal dissemination, distant metastasis, chemoresistance, and poor prognosis.

AB - Background/Aims: The aim of this study was to evaluate the association of genetic polymorphisms of p53, p21, and p73 genes with susceptibility to gastric carcinoma (GC), its clinicopathologic features, and prognosis. Methodology: In a case-control study including 419 controls and 389 patients with sporadic GC, single nucleotide polymorphisms (SNPs) of p53 Arg72Pro, p21 Ser31Arg, andp73 G4C14-to-A4T14 at exon 2 were genotyped. Tumor tissue was immunostained with p53 and examined for mutations in exons 5 to 8 of p53 using PCR -based single strand conformational polymorphism analysis and direct sequencing. Results: The SNPs of p53, p21, and p73 genes were not significantly associated with susceptibility to GC. p53 SNP (Pro/Pro) was significantly associated with increased risks for the following subgroups: invasive infiltration-type carcinoma (odds ratio [OR], 2.09; 95%CI, 1.01 to 4.34; p=0.048), carcinoma with peritoneal dissemination (OR, 3.42; 95%CI, 1.05 to 11.08; p=0.04), and carcinoma with distant metastasis (OR, 3.90; 95%CI, 1.14 to 13.38; p=0.03), but not with p53 immunoreactivity or mutations when compared with wild type. With respect to prognosis, p53 SNP (Pro/Pro) was an independent marker of poor overall survival in GC with TNM IB to IV stages (hazard ratio, 2.31; 95%CI, 1.14 to 4.69; p=0.02), especially in GC treated by chemotherapy (hazard ratio, 2.17; 95%CI, 1.06 to 4.41;p=0.03). Conclusions: This study provides evidence supporting the association of p53 SNP Arg72Pro with GC with invasive phenotype, peritoneal dissemination, distant metastasis, chemoresistance, and poor prognosis.

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Shirai O, Ohmiya N, Taguchi A, Nakamura M, Kawashima H, Miyahara R et al. p53, p21, and p73 gene polymorphisms in gastric carcinoma. Hepato-gastroenterology. 2010 Nov 1;57(104):1595-1601.