PMID- 21435097
OWN - NLM
STAT- MEDLINE
DCOM- 20111215
LR  - 20120131
IS  - 1440-1843 (Electronic)
IS  - 1323-7799 (Linking)
VI  - 16
IP  - 5
DP  - 2011 Jul
TI  - Hypoxia-inducible factor-1alpha polymorphisms are associated with genetic aberrations 
      in lung cancer.
PG  - 796-802
LID - 10.1111/j.1440-1843.2011.01972.x [doi]
AB  - BACKGROUND AND OBJECTIVE: The transcription factor, hypoxia-inducible factor-1 
      (HIF-1), is a master regulator of hypoxia, including repression of DNA repair 
      systems, resulting in genomic instability in cancer cells. The roles of the 
      polymorphic HIF-1alpha variants, C1772T (P582S) and G1790A (A588T), which are known 
      to enhance transcriptional activity, were evaluated in lung cancers. METHODS: 
      HIF-1alpha polymorphisms were assessed by direct sequencing in a total of 83 lung 
      cancer patients (42 adenocarcinomas, 30 squamous cell, four adenosquamous cell 
      and seven small cell lung carcinomas) and in 110 healthy control subjects. The 
      relationship between these polymorphisms and the frequently observed genetic 
      and/or epigenetic aberrations, TP53 loss of heterozygosity (LOH), 1p34 LOH, 
      retinoblastoma-1 (RB1) LOH, p16 inactivation and epidermal growth factor receptor 
      aberrations, was then assessed. RESULTS: There were no significant differences in 
      genotype frequencies for either C1772T or G1790A between lung cancer patients and 
      healthy controls. However, the frequency of the HIF1A C1772T variant allele was 
      significantly higher in lung cancer patients with TP53 LOH (P = 0.015). Among 
      adenocarcinoma patients, individuals with variant alleles of either polymorphism 
      showed significantly higher frequencies of TP53 LOH (P = 0.047), 1p34 LOH (P = 
      0.009), or either of these (P = 0.008) in the tumours. The in vitro 
      transcriptional activity of these HIF1A variants in A549 lung cancer cells was 
      significantly greater than that of the wild type under either normoxic or hypoxic 
      conditions, especially for P582S in cells containing mutant p53 (P < 0.0005 and P 
      < 0.005, respectively). CONCLUSIONS: These findings indicate that functional 
      polymorphisms in the HIF-1alpha gene may have an important impact on lung 
      carcinogenesis, especially in adenocarcinomas, possibly by increasing genomic 
      instability.
CI  - (c) 2011 The Authors; Respirology (c) 2011 Asian Pacific Society of Respirology.
FAU - Putra, Andika C
AU  - Putra AC
AD  - Department of Radiation Medicine, Research Institute for Radiation Biology and 
      Medicine, Hiroshima University, Hiroshima, Japan.
FAU - Tanimoto, Keiji
AU  - Tanimoto K
FAU - Arifin, Marina
AU  - Arifin M
FAU - Hiyama, Keiko
AU  - Hiyama K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Australia
TA  - Respirology
JT  - Respirology (Carlton, Vic.)
JID - 9616368
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Tumor Suppressor Protein p53)
SB  - IM
MH  - Adenocarcinoma/*genetics
MH  - Aged
MH  - Carcinoma, Adenosquamous/*genetics
MH  - Carcinoma, Squamous Cell/*genetics
MH  - Case-Control Studies
MH  - Gene Frequency/genetics
MH  - Genetic Predisposition to Disease/genetics
MH  - Genomic Instability/genetics
MH  - Genotype
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/*genetics
MH  - Loss of Heterozygosity/genetics
MH  - Lung Neoplasms/*genetics
MH  - Male
MH  - Middle Aged
MH  - Mutation/genetics
MH  - Polymorphism, Genetic/*genetics
MH  - Small Cell Lung Carcinoma/*genetics
MH  - Tumor Suppressor Protein p53/genetics
EDAT- 2011/03/26 06:00
MHDA- 2011/12/16 06:00
CRDT- 2011/03/26 06:00
PHST- 2011/03/26 06:00 [entrez]
PHST- 2011/03/26 06:00 [pubmed]
PHST- 2011/12/16 06:00 [medline]
AID - 10.1111/j.1440-1843.2011.01972.x [doi]
PST - ppublish
SO  - Respirology. 2011 Jul;16(5):796-802. doi: 10.1111/j.1440-1843.2011.01972.x.