Genetic Variations in the Hypoxia-Inducible Factor-1αGene and Lung Cancer

Abstract

Hypoxia-inducible factor-1 (HIF-1), an important genetic component of angiogenesis, becomes stable as a response to tumor hypoxia and facilitates tumor survival. The polymorphisms of the HIF-1alphagene may cause changes in the activity of this protein, which serves as a transcription factor for many genes in tumorigenesis. In this study, we have investigated the relationship between seven HIF-1alphapolymorphisms [C > T substitution in intron 8 (rs10873142), T418I (rs41508050) in exon 10, P564P (rs41492849), L580L (rs34005929), P582S (rs11549465), A588T (rs11549467) in exon 12 and dinucleotide GT repeats in intron 13 (rs10645014)] among lung cancer patients in the Turkish population. Genomic DNA was isolated from 141 lung cancer cases and 156 controls and subjected to PCR for amplification. Genotyping was carried out with RFLP and DNA sequencing methods. There was no significant difference between the lung cancer cases and controls in terms of the distribution of genotyping frequencies of seven HIF-1alphapolymorphisms (P > 0.05). No significant relationship was found between the C > T substitution in intron 8 and P582S haplotypes and development of lung cancer. In addition, there were no significant associations between the genotypes and clinopathological characteristics of the cases examined. These findings show that polymorphisms in the HIF-1alphagene do not confer susceptibility to lung cancer.

Hypoxia-Inducible Factor 1α Polymorphisms and Early-Stage Cervical Cancer

“…15,23,24 However, at present, no relationship was evident between HIF-1> polymorphisms and survival in patients with cervical cancer. Hypoxia-inducible factor 1> polymorphisms may not be a prognostic factor of cervical cancer, although we have adjusted the variance of treatments such as radiation therapy, which response was shown to be diminished in cases with overexpression of HIF-1>.…”

Update meta-analysis on 1790G/A polymorphism and cancer risk: Evidence from 26 studies

“…Overall,26 relevant studies involving 6337 cases and 9302 controls were selected in this metaanalysis [21,26,27,29,30,32,[43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62]. The main characteristics of these studies were shown in Table 1.…”

“…Genotype and allele distributions of 1790G/A polymorphism among cancer cases and controls and P value of HWE in controls were shown in Table 1 and 2. All studies were case-control studies, including three oral squamous cell carcinoma (OSCC) studies [46,51,59], three prostate cancer studies [29,44,60], three renal cell carcinoma studies [21,49,57], three breast cancer studies [30,32,50], two gynecologic carcinoma studies [27,53], two colorectal studies [26,62], two pancreatic cancer studies [55,58], three lung cancer studies [47,54,56] and the others(including head and neck squamous cell carcinoma(HNSCC) [43], transitional cell carcinoma of the bladder [45], hepatocellular carcinoma [52], gastric cancer [52], glottic cancer [61]). Cancers were histological or pathological in most studies.…”

“…Because a study by Tanimoto [64] showed both of the substitutions displayed an increased transactivation capacity of Hif-1/HIF-1α in vitro, the presence of the variant alleles might be associated with increased cancer susceptibility. However, studies focusing on the association of the Hif-1/HIF-1 polymorphism with cancer susceptibility had controversial conclusions [21,26,27,29,30,32,[43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59]. The lack of concordance across many of these studies reflects limitation in the studies, such as small sample sizes, ethnic difference and research methodology and so on.…”

Hypoxia-inducible factor-1: Physiological and Pathological Response to Hypoxia of Cell

“…27,28,29,30,31,32 İnsanda bulunan üç prolil hidroksilaz izoformu vardır (PHD1-3); normoksik koşullarda HIF-1alfa hidroksilasyonu için öncelikli sorumlunun PHD2 olduğu ileri sürülmüştür. 33,34 HIF-1alfa'nın VHL proteinine bağlanan tarafı oksijen-bağımlı degradasyon (ODD) böl-gesinde bulunur. ODD bölgesi HIF-1alfa'nın amino-terminal transaktivasyon domeyni N-TAD olarak bilinir.…”