Zoe Serefoglou

Genetic association of cytokine DNA polymorphisms with head and neck cancer

Mutations in oncogenes or tumor suppressor genes, as well as environmental factors such as tobacco chewing or smoking, poor oral hygiene, ill-fitting dental appliances, infection by certain HPV types, or alcohol abuse, seem to be involved in the multifactorial process of carcinogenesis in head and neck. Recently, several genetic association studies have indicated that common DNA polymorphisms in low penetrance genes may affect the susceptibility of an individual to malignancy. Cytokines are an important group of proteins that regulate and mediate inflammation and angiogenesis. Tumor growth, invasion and metastasis are facilitated when there is a deregulation in their production. Cytokines include interleukins (ILs), tumor necrosis factors (TNFs) and certain growth factors (GFs). A number of genetic association studies have recently investigated the putative correlation between functional DNA polymorphisms in cytokine genes and head and neck carcinomas. This review discusses the findings of such studies in oral, nasopharyngeal and esophageal squamous cell carcinomas. Extensive research has indicated that functional polymorphisms affecting gene expression of IL-4,-6,-8,-10 as well as TNF-alpha are strongly associated with increased risk for oral cancer. Gene expression of TNF-alpha seems to be associated also with esophageal carcinomas, while for nasopharyngeal cancer the picture is yet unclear. It is generally believed that such genetic association studies will gradually increase our knowledge regarding the predisposed manifestation and advancement of these malignancies in the head and neck region.

Common Gene Polymorphisms Associated with Thrombophilia

Genetic association studies have revealed a correlation between DNA variations in genes encoding factors of the hemostatic system and thrombosis-related disease. Certain var‐ iant alleles of these genes that affect either gene expression or function of encoded protein are known to be genetic risk factors for thrombophilia. The chapter presents the current genetics and molecular biology knowledge of the most important DNA polymorphisms in thrombosis-related genes encoding coagulation factor V (FV), coagulation factor II (FII), coagulation factor XII (FXII), coagulation factor XIII A1 subunit (FXIIIA1), 5,10methylene tetrahydrofolate reductase (MTHFR), serpine1 (SERPINE1), angiotensin I-con‐ verting enzyme (ACE), angiotensinogen (AGT), integrin A2 (ITGA2), plasma carboxypeptidase B2 (CPB2), platelet glycoprotein Ib α polypeptide (GP1BA), thrombo‐ modulin (THBD) and protein Z (PROZ). The molecular detection methods of each DNA polymorphism is presented, in addition to the current knowledge regarding its influence on thrombophilia and related thrombotic events, including stroke, myocardial infarction, deep vein thrombosis, spontaneous abortion, etc. In addition, best thrombosis prevention strategies with a combination of genetic counseling and molecular testing are discussed.