Impact of TP53 codon 72 and MDM2 SNP 309 polymorphisms in pancreatic ductal adenocarcinoma.
Single-nucleotide polymorphisms (SNPs) of TP53 (codon 72, rs1042522) and MDM2 promoter (SNP 309, rs2279744) have been associated with risk for various human cancers. However, studies analyzing these polymorphisms in pancreatic ductal adenocarcinoma (PDAC) are lacking. We investigated TP53 codon 72 a...
Saved in:
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2015-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0118829&type=printable |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849724175547105280 |
|---|---|
| author | Yasuki Hori Katsuyuki Miyabe Michihiro Yoshida Takahiro Nakazawa Kazuki Hayashi Itaru Naitoh Shuya Shimizu Hiromu Kondo Yuji Nishi Shuichiro Umemura Akihisa Kato Hirotaka Ohara Hiroshi Inagaki Takashi Joh |
| author_facet | Yasuki Hori Katsuyuki Miyabe Michihiro Yoshida Takahiro Nakazawa Kazuki Hayashi Itaru Naitoh Shuya Shimizu Hiromu Kondo Yuji Nishi Shuichiro Umemura Akihisa Kato Hirotaka Ohara Hiroshi Inagaki Takashi Joh |
| author_sort | Yasuki Hori |
| collection | DOAJ |
| description | Single-nucleotide polymorphisms (SNPs) of TP53 (codon 72, rs1042522) and MDM2 promoter (SNP 309, rs2279744) have been associated with risk for various human cancers. However, studies analyzing these polymorphisms in pancreatic ductal adenocarcinoma (PDAC) are lacking. We investigated TP53 codon 72 and MDM2 SNP 309 polymorphisms in 32 patients with PDAC, 16 patients with chronic pancreatitis (CP), and 32 normal controls, using formalin-fixed paraffin-embedded tissue. We also examined TP53 and MDM2 protein immunohistochemistry (IHC) to assess the involvement of these differences in malignant transformation and disease progression. TP53 Pro/Pro genotype was significantly more frequent in PDAC patients than in controls (65.6 vs. 15.6%, p < 0.001) and no significant difference was found between CP patients (37.5%) and controls. In MDM2 SNP 309, there were no significant differences among the three groups. Based on the Kaplan-Meier analysis, overall survival was significantly shorter in MDM2 G/G genotypes compared with other genotypes (G/T and T/T) (359 vs. 911 days, p = 0.016) whereas no significant differences in TP53 genotypes were observed (638 vs. 752 days, p = 0.471). Although TP53 IHC was frequent in PDAC patients (53.1%), TP53 and MDM2 protein expression was not correlated with polymorphisms. Our study demonstrated TP53 codon 72 polymorphism is potentially a genetic predisposing factor while MDM2 SNP 309 polymorphism might be useful in predicting survival outcome. |
| format | Article |
| id | doaj-art-c27ba4599ac249f7bf29a58cd50b3899 |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-c27ba4599ac249f7bf29a58cd50b38992025-08-20T03:10:49ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01103e011882910.1371/journal.pone.0118829Impact of TP53 codon 72 and MDM2 SNP 309 polymorphisms in pancreatic ductal adenocarcinoma.Yasuki HoriKatsuyuki MiyabeMichihiro YoshidaTakahiro NakazawaKazuki HayashiItaru NaitohShuya ShimizuHiromu KondoYuji NishiShuichiro UmemuraAkihisa KatoHirotaka OharaHiroshi InagakiTakashi JohSingle-nucleotide polymorphisms (SNPs) of TP53 (codon 72, rs1042522) and MDM2 promoter (SNP 309, rs2279744) have been associated with risk for various human cancers. However, studies analyzing these polymorphisms in pancreatic ductal adenocarcinoma (PDAC) are lacking. We investigated TP53 codon 72 and MDM2 SNP 309 polymorphisms in 32 patients with PDAC, 16 patients with chronic pancreatitis (CP), and 32 normal controls, using formalin-fixed paraffin-embedded tissue. We also examined TP53 and MDM2 protein immunohistochemistry (IHC) to assess the involvement of these differences in malignant transformation and disease progression. TP53 Pro/Pro genotype was significantly more frequent in PDAC patients than in controls (65.6 vs. 15.6%, p < 0.001) and no significant difference was found between CP patients (37.5%) and controls. In MDM2 SNP 309, there were no significant differences among the three groups. Based on the Kaplan-Meier analysis, overall survival was significantly shorter in MDM2 G/G genotypes compared with other genotypes (G/T and T/T) (359 vs. 911 days, p = 0.016) whereas no significant differences in TP53 genotypes were observed (638 vs. 752 days, p = 0.471). Although TP53 IHC was frequent in PDAC patients (53.1%), TP53 and MDM2 protein expression was not correlated with polymorphisms. Our study demonstrated TP53 codon 72 polymorphism is potentially a genetic predisposing factor while MDM2 SNP 309 polymorphism might be useful in predicting survival outcome.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0118829&type=printable |
| spellingShingle | Yasuki Hori Katsuyuki Miyabe Michihiro Yoshida Takahiro Nakazawa Kazuki Hayashi Itaru Naitoh Shuya Shimizu Hiromu Kondo Yuji Nishi Shuichiro Umemura Akihisa Kato Hirotaka Ohara Hiroshi Inagaki Takashi Joh Impact of TP53 codon 72 and MDM2 SNP 309 polymorphisms in pancreatic ductal adenocarcinoma. PLoS ONE |
| title | Impact of TP53 codon 72 and MDM2 SNP 309 polymorphisms in pancreatic ductal adenocarcinoma. |
| title_full | Impact of TP53 codon 72 and MDM2 SNP 309 polymorphisms in pancreatic ductal adenocarcinoma. |
| title_fullStr | Impact of TP53 codon 72 and MDM2 SNP 309 polymorphisms in pancreatic ductal adenocarcinoma. |
| title_full_unstemmed | Impact of TP53 codon 72 and MDM2 SNP 309 polymorphisms in pancreatic ductal adenocarcinoma. |
| title_short | Impact of TP53 codon 72 and MDM2 SNP 309 polymorphisms in pancreatic ductal adenocarcinoma. |
| title_sort | impact of tp53 codon 72 and mdm2 snp 309 polymorphisms in pancreatic ductal adenocarcinoma |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0118829&type=printable |
| work_keys_str_mv | AT yasukihori impactoftp53codon72andmdm2snp309polymorphismsinpancreaticductaladenocarcinoma AT katsuyukimiyabe impactoftp53codon72andmdm2snp309polymorphismsinpancreaticductaladenocarcinoma AT michihiroyoshida impactoftp53codon72andmdm2snp309polymorphismsinpancreaticductaladenocarcinoma AT takahironakazawa impactoftp53codon72andmdm2snp309polymorphismsinpancreaticductaladenocarcinoma AT kazukihayashi impactoftp53codon72andmdm2snp309polymorphismsinpancreaticductaladenocarcinoma AT itarunaitoh impactoftp53codon72andmdm2snp309polymorphismsinpancreaticductaladenocarcinoma AT shuyashimizu impactoftp53codon72andmdm2snp309polymorphismsinpancreaticductaladenocarcinoma AT hiromukondo impactoftp53codon72andmdm2snp309polymorphismsinpancreaticductaladenocarcinoma AT yujinishi impactoftp53codon72andmdm2snp309polymorphismsinpancreaticductaladenocarcinoma AT shuichiroumemura impactoftp53codon72andmdm2snp309polymorphismsinpancreaticductaladenocarcinoma AT akihisakato impactoftp53codon72andmdm2snp309polymorphismsinpancreaticductaladenocarcinoma AT hirotakaohara impactoftp53codon72andmdm2snp309polymorphismsinpancreaticductaladenocarcinoma AT hiroshiinagaki impactoftp53codon72andmdm2snp309polymorphismsinpancreaticductaladenocarcinoma AT takashijoh impactoftp53codon72andmdm2snp309polymorphismsinpancreaticductaladenocarcinoma |