PMID- 21709439
OWN - NLM
STAT- MEDLINE
DCOM- 20120126
LR  - 20220309
IS  - 1555-8576 (Electronic)
IS  - 1538-4047 (Linking)
VI  - 12
IP  - 5
DP  - 2011 Sep 1
TI  - Polymorphisms in the hypoxia-inducible factor-1alpha gene confer susceptibility to 
      pancreatic cancer.
PG  - 383-7
AB  - The transcription factor hypoxia-inducible factor-1 (HIF-1) has alpha and beta subunits. 
      Recent studies have shown that the HIF-1alpha gene may have C1772T and G1790A single 
      nucleotide polymorphisms (SNPs). These SNPs may increase the stability and 
      activity of HIF-1alpha. In the present study, we looked for these SNPs by genotyping 
      circulating mononuclear cells from 263 patients with pancreatic ductal 
      adenocarcinoma (PDAC), using 271 healthy volunteers as controls. As a result, 
      both SNPs were more frequent in PDAC patients than in healthy volunteers (C1772T: 
      21 vs. 11%, p < 0.01; G1790A: 25 vs. 8%, p < 0.01). Further, both SNPs were 
      associated with higher risks for PDAC (C1772T: OR=2.156, 95% CI: 1.324-3.511, p < 
      0.05; G1790A: OR=3.716, 95% CI: 2.213-6.238, p < 0.01). We also stained HIF-1alpha by 
      immunohistochemistry in 68 PDAC tumors to examine their HIF-1alpha expression levels. 
      To this end, we designed a semi-quantitative method that was based on the 
      staining intensity and frequency of HIF-1alpha-positive cells. As a result, the 
      G1790A SNP, but not C1772T SNP, was associated with an increased HIF-1alpha 
      expression. We also related genotyping data to patient's survival times, serum 
      CA19-9, and tumor's volumes, grades, stages and lymph-node metastasis. The C1772T 
      SNP was not associated with any of these parameters. In contrast, the G1790A SNP 
      was associated with increases in serum CA19-9 and in tumor volumes. In 
      conclusion, the C1772T and G1790A SNPs in the HIF-1alpha gene increase the 
      susceptibility to pancreatic cancer. In addition, the G1790A SNP is associated 
      with increases in tumor-produced HIF-1alpha and in the progression of the cancer.
FAU - Wang, Xiuchao
AU  - Wang X
AD  - Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
FAU - Liu, Yingwei
AU  - Liu Y
FAU - Ren, He
AU  - Ren H
FAU - Yuan, Zhanna
AU  - Yuan Z
FAU - Li, Shasha
AU  - Li S
FAU - Sheng, Jun
AU  - Sheng J
FAU - Zhao, Tiansuo
AU  - Zhao T
FAU - Chen, Yong
AU  - Chen Y
FAU - Liu, Fenghua
AU  - Liu F
FAU - Wang, Feng
AU  - Wang F
FAU - Huang, He
AU  - Huang H
FAU - Hao, Jihui
AU  - Hao J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110901
PL  - United States
TA  - Cancer Biol Ther
JT  - Cancer biology & therapy
JID - 101137842
RN  - 0 (CA-19-9 Antigen)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - CA-19-9 Antigen/blood
MH  - Carcinoma, Pancreatic Ductal/*genetics
MH  - Female
MH  - *Genetic Predisposition to Disease
MH  - Genotype
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/*genetics/metabolism
MH  - Leukocytes, Mononuclear/cytology
MH  - Lymphatic Metastasis
MH  - Male
MH  - Middle Aged
MH  - Pancreatic Neoplasms/*genetics
MH  - *Polymorphism, Single Nucleotide
EDAT- 2011/06/29 06:00
MHDA- 2012/01/27 06:00
CRDT- 2011/06/29 06:00
PHST- 2011/06/29 06:00 [entrez]
PHST- 2011/06/29 06:00 [pubmed]
PHST- 2012/01/27 06:00 [medline]
AID - 15982 [pii]
AID - 10.4161/cbt.12.5.15982 [doi]
PST - ppublish
SO  - Cancer Biol Ther. 2011 Sep 1;12(5):383-7. doi: 10.4161/cbt.12.5.15982. Epub 2011 
      Sep 1.