title: Association of hypoxia inducible factor-1α polymorphisms with susceptibility to non-small-cell lung cancer.
abstract: Hypoxia-inducible factor-1α (HIF-1α) is a key regulator of cellular response to hypoxia and has been suggested to play an important role in tumorigenesis and metastasis. The aim of this study was to investigate the role of HIF-1α-1772 C/T (P582S) and -1790 G/A (A588T) polymorphisms in the susceptibility to and severity of non-small-cell lung cancer (NSCLC). Using a case-control study design and polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) analysis, the allele frequencies and genotype distributions of each single nucleotide polymorphism in 285 NSCLC cases and 300 gender-matched controls were compared. The distribution of the genotype frequencies of HIF-1α-1772 C/T and -1790 G/A were significantly different between the NSCLC and the controls. Logistic regression analysis revealed that higher odds ratios (ORs) for lung cancer were observed for individuals with HIF-1α-1772 T/T genotype against CC/CT genotypes (an OR of 4.04, 95% confidence interval [CI] = 2.02-8.08, P = 0.0001), and HIF-1α-1790 A/A genotype against GG/GA genotypes (an OR of 4.42, 95% CI 2.22-8.78, P < 0.0001). There were no relationship between HIF-1α-1772 C/T or -1790 G/A allele distribution and disease severity of NSCLC (P > 0.05). However, those patients carrying a HIF-1α-1772 T/T genotype or a HIF-1α-1790 A/A had a tendency toward inferior prognosis compared with other patients.
authors.affiliation: Department of Medicine, Armed-Force Taichung General Hospital, Taiwan, Republic of China.
authors.forename: Wu-Hsien
authors.initials: WH
authors.lastname: Kuo
authors.forename: Chuen-Ming
authors.initials: CM
authors.lastname: Shih
authors.forename: Chiao-Wen
authors.initials: CW
authors.lastname: Lin
authors.forename: Wei-Erh
authors.initials: WE
authors.lastname: Cheng
authors.forename: Shuo-Chueh
authors.initials: SC
authors.lastname: Chen
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Yao-Ling
authors.initials: YL
authors.lastname: Lee
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics; D000368:Aged; D000483:Alleles; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics*; D016015:Logistic Models; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D012307:Risk Factors
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit