Role of genetic polymorphisms in the angiogenesis pathway and non-small-cell lung cancer tumor behavior: implications in risk assessment and clinical outcome

Abstract

Lung cancer is a highly prevalent disease worldwide. Currently, it is the leading cause of cancer-related deaths in Western nations. Non-small-cell lung cancer (NSCLC) corresponds to approximately 85% of all histological types. Risk factors are usually associated with tobacco consumption, occupational exposure, radon, and passive smoking. Lung cancer diagnosis often occurs in the advanced stages IIIB and IV. Thus systemic therapies, such as cytotoxic agents and therapeutic targets, play a major role in NSCLC management. To date, many factors influence NSCLC behavior and, therefore, clinical response to therapeutic targets, such as epidermal growth factor (EGF) and its receptor (EGFR) and vascular endothelial growth factor (VEGF) and its receptor (VEGFR). Angiogenesis-related genetic polymorphisms are of primary interest in NSCLC research. Recently, a Portuguese study identified the EGF +61 A/G polymorphism as a risk factor for NSCLC patients with advanced stages of cancer. Furthermore, other genetic polymorphisms, such as VEGF −2578 C/A and VEGF −1154 G/A, were correlated with increased tumor VEGF expression, vascular density, and poor survival. This topic will address research involving angiogenesis genetic polymorphisms and NSCLC behavior.