Original article
Clinical
Genetic Polymorphism of VEGF-1154 (A/G) in Laryngeal Squamous Cell Carcinoma

https://doi.org/10.1016/j.arcmed.2007.09.008Get rights and content

Background

Angiogenesis has been shown to be increased in various human tumors including head and neck squamous cell carcinoma (SCC). Vascular endothelial growth factor (VEGF) is thought to be one of the most important angiogenic factors in tumorigenesis. In this study, we aimed to investigate whether polymorphism of VEGF-1154 (A/G) genotypes are associated with the risk of laryngeal SCC.

Methods

A prospective, randomized, case-control study in a tertiary university hospital was done. The study group consisted of 57 Caucasian patients with laryngeal SCC and 89 control subjects. Blood samples were obtained before surgery or from the patients under follow-up to 5 years after surgery. VEGF-1154 (A/G) genotypes were detected by real-time polymerase chain reaction with thermal cycler system.

Results

According to the high-risk (GG) genotype, the difference between the patient and control groups was statistically significant (OR 0.43, 95% CI = 0.19–0.95, p = 0.037).

Conclusions

GG genotype of the VEGF gene may increase the risk of laryngeal SCC in this population. VEGF gene polymorphism may be an important potential genetic and therapeutic marker of laryngeal SCC.

Introduction

Squamous cell carcinoma (SCC) of the larynx is one of the most frequent malignancies occurring in the head and neck region. The intensity of angiogenesis has been shown to be increased in various human tumors including head and neck SCC (HNSCC). It is now generally accepted that tumor angiogenesis is important both for the growth of a primary neoplastic tumor and also for the development of metastasis (1). Among these angiogenic factors, vascular endothelial growth factor (VEGF) is thought to be one of the most important. VEGF induces the proliferation, differentiation, and migration of vascular endothelial cells; increases the permeability of the capillaries; and enhances the survival of endothelial cells by preventing their apoptosis 2, 3, 4. In several studies, increased microvessel density and overexpression of VEGF in HNSCC was also associated with metastasis, recurrence, and poor prognosis. However, the association between angiogenesis and tumorigenesis of HNSCC is not well defined 5, 6. Genetic host factors, including the VEGF genotype, must also contribute to the laryngeal cancer development mechanisms. Several single nucleotide polymorphisms have been described in the VEGF gene, some of which have been shown to be associated with differential expression of VEGF in vitro, and two of them (positions −2578 and −1154) are located in the VEGF promoter (7). The aim of this study is to investigate the possible relation between the VEGF-1154 (A/G) gene polymorphism and the laryngeal SCC.

Section snippets

Materials and Methods

The study group consisted of 57 Caucasian patients with laryngeal SCC. There were 54 men with a mean age of 55 years (range, 37–72 years) and three women with a mean age of 47 years (range, 32–55 years) and 89 control subjects, 53 men and 36 women; mean age 50 years (range, 28–73 years). This was a hospital-based case-control study conducted at the University of Mersin Hospital from 1999 to 2006. Patients and control subjects were from the same geographic region (southern Turkey) and of the

Results

The AA genotype was not seen in both patient and control groups. The AG genotype was 56% in patient group and 37.08% in control group, respectively. The GG genotype was detected in a rate of 44% in patient group, and 62.92% in control group, respectively. According to the high-risk (GG) genotype, the difference between the patient and control groups was statistically significant (OR 0.43, 95% CI = 0.19–0.95, p = 0.037). Table 2 summarizes the genotype and allelic frequencies of the study and

Discussion

The VEGF genotype divides into low expression (homozygote AA), intermediate (heterozygote AG) and high expression (homozygote GG) phenotypes by Mendelian inheritance. We hypothesized that patients with high expression of VEGF genotype have more aggressive and metastatic tumor behavior than low expression or heterozygote genotypes. To our knowledge, this is the first study investigating this relationship in the Western literature, and according to the high-risk (GG) genotype, the difference

References (16)

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