Introduction to Oncogene Concept

**3**

cancers.

**Chapter 1**

Introductory Chapter: Interactions

Chemicals and KRAS Oncogene in

v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) is an oncogene.

Most oncogenes are expressed as proto-oncogenes, involved in cell growth and proliferation or inhibition of apoptosis. If there are chemical, physical, or biological factors that cause mutations in such genes promoting cellular growth, these genes are mostly upregulated and cellular proliferation increases [1]. The cascade of events leading to proliferation usually predisposes the cell to cancer. In this case,

The KRAS gene is located on the twelfth chromosome and belongs to the Ras family of oncogenes. These proteins play important roles in cell division, cell differentiation, and apoptotic cell death. Induction of KRAS with different environmental chemicals leads to high expression of K-Ras protein, which in turn causes high cellular proliferation. These cascade of events finally initiate certain types of cancers, particularly colorectal (CRC), pancreatic, and lung cancers. High calorie intake, diets rich in meat and fat, smoking, and alcohol consumption are the major risk factors of CRCs, and it was estimated that in CRC, mutated KRAS has an incidence of ∼50%. Exposure to certain environmental chemicals [organochlorine insecticides such as DDT and its metabolite dichlorodiphenyltrichloroethylene (DDE); herbicides such as EPTC and pendimethalin; N-nitrosamines; polychlorinated biphenyls (PCBs); benzene] and drugs (anti-diabetics drugs) can also contribute to the increased incidence of PC throughout the world. It was stated that in adenocarcinomas of the pancreas, mutated KRAS has an incidence of ∼70–90%. Lung cancer is the leading cause of deaths worldwide. KRAS gene mutations are much more common in long-term tobacco smokers with lung cancer when compared to nonsmokers. KRAS gene mutations are observed in 15–25% of all lung cancer cases, being more frequent in whites vs. Asian populations. Lung cancers with KRAS gene mutations typically indicate a poor prognosis and are associated with resistance to several cancer treatments. This chapter mainly focuses on KRAS, interactions between environmental chemicals, and KRAS oncogene in different cancers, particularly in colorectal, pancreatic, and lung

Different Cancers - Special Focus

on Colorectal, Pancreatic, and

between Environmental

Lung Cancers

*Pinar Erkekoglu*

**1. Introduction**
