Introduction
Lung cancer has been the leading cause of cancer-related deaths in Korea, and its incidence continues to rise [1]. Despite therapeutic advances, the overall 5-year survival remains only 15% [2]. Lung cancer is a multicellular and multistage process that involves a number of genetic changes in oncogenes and tumor suppressor genes. Nevertheless, the prognosis of lung cancer has remained poor despite innovations in diagnostic testing and surgical technique and the development of new chemotherapeutic agents. Recently introduced targeted agents show different responses according to histological subtype, and the efficiency of treatment modalities for lung cancer depends on the time of diagnosis [3]. Therefore, there is a great need for rapid and efficient early detection methods. For developing improved molecular biomarkers for the early detection and prediction of response to chemotherapy, it is important to identify genetic alterations specific to each subtype of lung cancer. Single-nucleotide polymorphisms (SNPs) represent an important class of genetic variations and affect an individual's susceptibility to disease in certain circumstances [4-6].
Activation of the intracellular survival signal transduction protein AKT, known as protein kinase B, has been proposed as a central signaling event in carcinogenesis and has been shown in experimental models to confer resistance to chemotherapy and radiation [7, 8]. AKT is activated by phosphatidylinositol 3 phosphates, the products of phosphoinositide 3-kinase (PI3K) activity [9]. Additionally, AKT activity is commonly dysregulated in a variety of human tumors because of frequent inactivation of the PTEN tumor suppressor gene, which negatively regulates phosphatidylinositol 3 phosphate levels, and alterations of this gene have been identified in various cancers, including lung cancer [10, 11]. To date, 3 human isoforms of AKT have been identified, AKT1, AKT2, and AKT3, which are expressed in lung, breast, colon, and prostate tumor tissues [12].
Somatic mutations of AKTs have been reported in endometrial carcinomas, hypoglycemia, and breast cancer [13, 14]. However, somatic mutations in AKT families are rare in lung cancer [15, 16]. Previously, it was reported that an AKT1 polymorphism was not associated with schizophrenia [17, 18]. AKT1 and AKT2 polymorphisms have been reported to be related to survival of esophageal cancer [19], and it was reported that an AKT1 polymorphism was associated with survival in surgically resected non-small cell lung cancer [20]. However, the association between AKT2 and AKT3 polymorphisms and the risk of lung cancer has not yet been clarified. This study discovered polymorphisms of the AKT2 and AKT3 promoter regions and their relation with the risk of lung cancer in a Korean population.