**1. Introduction**

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

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, they are termed as "oncogenes" [1, 2]. These genes are mutated and/or overexpressed at high levels in tumor cells. Normally, cells repair themselves or undergo apoptosis if there is an interruption on the cell cycle. However, the high expression of multiple oncogenes, along with mutated apoptotic and/or tumor suppressor genes and exposure to environmental chemicals that trigger such mutations can all act in concert and finally cause tumorigenesis [1–3]. In the past 50 years, several oncogenes have been identified in different types of human cancers. There are many cancer drugs that target the proteins encoded by oncogenes [1–3].

Genetic and environmental interactions usually determine the profiles of cancers. v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) is a very important oncogene for the initiation of cancer [1]. It is usually found to be mutated in different types of cancer, particularly in colorectal cancers (CRCs), pancreatic cancer (PC), and lung cancer [4–6]. Concerning KRAS, different chemicals such as polychlorinated biphenyls (PCBs), certain antidiabetic drugs, and pesticides may be leading causes of KRAS mutations, and such mutations increase the expression of K-Ras protein in different tissues, leading to high cellular proliferation and finally carcinogenesis [7–9]. This chapter mainly focuses on CRCs, PC, and lung cancer and KRAS. Moreover, the interactions between KRAS mutations and environmental factors in these particular cancers will also be mentioned.
