Which environment makes cancer?

Cancer occurs with uncontrolled cell growth or abnormal cell division in DNA damage. Carcinogens are the factors that cause DNA mutations and they are known to cause cancer in our body by making changes in gene level. Genetic susceptibility is also important in cancer development along with factors such as poor living conditions. Additionally, all these environmental factors such as X-rays, gamma rays, the radiation emitted from radioactive materials, aniline type dyes, cigarette, free radicals, asbestos, silica dust, air pollution, food additives, various drugs, some of the chemicals used in perfumes, oncogenic viruses and bacteria are playing an important role in cancer formation and contribute the increase of incidence of cancer. The environmental factors that cause cancer are located in air, water, soil and the food that we need to live. Consequently, human get cancer from exposure to carcinogens from the environment where they live. The cancer is a difficult disease to treat and reduces the life quality of people with cancer. Investigation of the effects of environmental factors in cancer and prevention of the cancer development by determining the factors that cause cancer are very important from this perspective. *Correspondence to: Suleyman Kaleli, Faculty of Medicine, Department of Medical Biology, Sakarya University, 54187, Sakarya Turkey, Tel: +902642953117; E-mail: skaleli@sakarya.edu.tr This manuscript was presented as oral presentation in ISEM2016, 3rd International Symposium on Environment and Morality, 4-6 November 2016, Alanya – Turkey


Introduction
Cancer, which is the second leading cause of death, is a group of disease involving abnormal cell growth with the potential to invade or spread to other parts of the body [1,2]. According to GLOBOCAN, there were about 14.1 million new cancer cases, 8.2 million cancer deaths and 32.6 million people living with cancer within 5 years of diagnosis in 2012 worldwide. On the other hand, it is estimated that 1,685,210 new cases of cancer will be diagnosed in the United States and 595,690 people will die from the disease in 2016. Thus, there is an urgent need for a new therapeutic strategy to reduce cancer-related deaths [3,4].
Cancer is a multifactorial disease. Most genetic factors and environmental factors such as viruses, bacteria, radiation and eating habits and chemicals increase the risk of developing cancer [3][4][5][6][7][8] (Figure  1). 10-15% of all cancers are thought to be related to heredity, as for the rest, 85-90% of cancer have their roots in the environment and lifestyle.
It is known that approximately 25-30% of tobacco, 30-35% of diet, 15-20% of infections and the remaining percentage of other factors like radiation, stress, physical activity, environmental pollutants, etc. cause cancer related mortality [9]. In terms of genetic factors, the mutations in multiples genes, including oncogenes, tumor suppressor genes and DNA repair genes can lead to cancer formation rather than a single gene. These genes cause cancer through three main biologic pathways [cell cycle, apoptosis and differentiation], which are normally, regulate tissue homeostasis and cell growth [9]. For this purpose, the aim of this study was to discuss the interactions of genetic factors with various environmental factors, including diet, lifestyle, metabolic alterations, and various environmental exposures.

The relationship between cancer and genetics
Inherited genetic factors play an important role in cancer development. The mutation of critical genes, including tumorsuppressor genes, oncogenes and genes involved in DNA repair, leads to genetic instability and cancer development. Several genes related to inherited cancers have been identified on leukemia, certain childhood tumors, colon and especially breast and ovarian cancer. [10]. For example, germline mutations in breast cancer gene 1 [BRCA1] represent a predisposing genetic factor in 15-45% of hereditary breast cancers. Female mutation carriers have a 60-80% lifetime risk for developing breast cancer [11,12] and a 20-40% lifetime risk of developing ovarian cancer [13][14][15]. Furthermore, mutations in APC gene or mismatch DNA repair genes lead to two different types of inherited colon cancer

Radiation
Radiation is classified into two fundamental categories as nonionizing and ionizing radiation. Ionizing radiation is identified as X-rays, which forms electrically charged particles or ions [17]. X-rays and gamma rays are especially used for medical imaging [16,19]. Computed tomography [CT] is a radiological method that generates a three-dimensional image for the diagnosis of various diseases [20]. It has been described in several studies that diagnostic X-rays lead to cause mutations and up to 10% of invasive cancers are related to radiation exposure [21][22][23][24][25][26]. With regard to this concern, large cohorts of patients treated with radiotherapy for cervical cancer, breast cancer, Hodgkin lymphoma, testicular cancer, and childhood cancer have been followed for decades. Increased levels of screening in a radiationexposure is known of the risk of cancer incidence. In this respect, the biological impact can change according to the dose equivalent of radiation [27][28][29][30].

Heavy metals
Exposure to various chemicals and heavy metals depending on exposed dose, genetics, people's immune resistance and overall health status, age, the level of nutrition has been associated with risk of different cancers, including breast cancer, pancreatic, lung cancer, and gallbladder cancer etc. [10]. When metals get into the body through air, food, water, or dermal exposure, they exert their enzymatic and genotoxic effects on different organs [31]. Some heavy metals such as arsenic, cadmium, chromium, nickel, and zinc are known as developing cancer. They bind to vital cellular components, such as structural proteins, enzymes, and nucleic acids [32]. For instance, the effect of cadmium on the lung and prostate cancer has been determined [33]. The toxicological effects of zinc were determined in experimental animals [34]. Additionally, there may be a relationship between exposure to certain metal compounds and the risk of breast cancer [35]. However, there is urgently needed the experimental animal studies, and epidemiologic studies associated metals with cancer.

Cigarette
Chemicals in cigarette smoke cause DNA damage and have been increasing the risk of various cancers, particularly primary lung cancer [3][4][5][6][7][8][9][10]. It is known that nearly 9 out of 10 lung cancers are caused by cigarette smoking. Cigarettes cause about 1.5 million deaths from lung cancer per year and it is estimated that a number will rise to nearly 2 million per year by the 2020s or 2030s [6].

Foods and nutrition
Dietary factors have been associated with 30% of cancers in Western countries. In fact, making diet is a second factor after tobacco as a preventable cause of cancer. The effects diet on cancer risk in developing countries has been considered around 20% [37]. On the other hand, some parts of additives have carcinogenic effects. For example, the dulce, cinnamyl anthranilate and thiourea like synthetic additives, which cause liver cancer, have been identified in some experiments and thus, they are forbidden to use these substances in foods [38][39][40]. However, some substances, including nitrite salts, sodium nitrite [E250] or potassium nitrite [E249] have been used despite of increasing the risk of cancer. Meat products such as sausage as antibacterial and color holder include these substances. This type of processed meat products increases the risk of bowel cancer by 21% [41]. Unfortunately, an excess of consumption of sugar and salt, which are the two main foods, causes obesity and an increase in insulin and so, higher level of these substances indirectly increase the risk of cancer [42]. Besides, aflatoxins are found in the groundnut, pulses, oilseeds and grains and they increase the risk of hepatocellular carcinoma [11].

Free radicals and ROS
Free radicals and ROS have been associated with the increased risk of cancer [12]. Particularly free radicals cause cancer and atherosclerosis diseases. The free radicals lead to cancer initiation and promotion by chromosomal defects and oncogene activation. On the other hand, ROS, such as super oxide anion, hydrogen peroxide, hydroxyl radical, and nitric oxide and their biological metabolites also play an important role in carcinogenesis. ROS induce DNA damage including double strand break, base modification and DNA protein cross-links [43].

Air pollution
Emissions from motor vehicles, industrial processes, power generation, the household combustion of solid fuel, and other sources pollute the ambient air across have global effect in the world. The chemical and physical features of ambient air pollution can vary according to sources of pollution, climate, and meteorology. However, the specific chemicals in the air pollution are known to be carcinogenic to humans. In 1971, the US Clean Air Act was established and ozone, particulate matter, sulfur dioxide, nitrogen dioxide, carbon monoxide and lead were defined as air pollutants. Furthermore, 189 toxic and hazardous air pollutants have been identified [44]. Exposure to ambient fine particles [PM2.5] was recently estimated to have contributed 3.2 million premature deaths worldwide in 2010, due largely to cardiovascular disease, and 223.000 deaths from lung cancer [45,46]. These air pollutants cause to acute illness such as vomiting, chronic diseases such as cancer, as well as immunologic, neurologic, reproductive, developmental and respiratory diseases. Exposure of these chemicals increases the risk of pleural and peritoneal tumors and lung cancer incidence [47][48][49][50].

Oncogenic viruses
Oncoviruses or tumor viruses are a general term used for viruses. This term began to use in 1950-60 years to show acute conversion. Nowadays, it means any virus containing DNA or RNA genome and thus, it is synonymous with "tumor virus" or "cancer virus". However, the majority of viruses does not cause cancer in humans or animals [51].  [EBV] have been associated with the risk of cancer [13]. It is estimated that viral infections contribute to 15-20% of all human cancers [52]. Thus, these cancers [e.g. Papillomavirus vaccines] can be prevented by vaccination and can be detected with a simple blood test and can be treated with antiviral compounds.

Discussion
New areas of cancer research are focusing on the potential for pollutants to interact with one another and with genetic factors. The exact cause or causes of cancer have not known exactly. However, certain genes that tend to cancer interact with some environmental factors such as viruses, exposure to radiation, various chemicals and pollutants are related to increasing the risk of cancer. Carcinogens have an effect on damaging DNA, disrupting hormones, inflaming tissues, or switching genes on or off [53]. On the other hand, there is substantial evidence that synergism between two different exposures can cause some cancers. Asbestos, for example, enhances the carcinogenicity of tobacco smoke, so the rate of lung cancer was especially high among people who smoked and were exposed to asbestos in their workplaces [53]. Consequently, the environment is often used with a broad scope in the medical literature and it is known that the environmental factors have been increased the risk of cancers [54]. Thus, more studies that are detailed are needed to determine the exact effects of environmental factors on cancer development.

Conclusion
People can avoid some cancer-causing exposures, such as tobacco smoke and the sun rays. However, other environmental risk factors including air, water, food pollutants cannot be prevented due to consisting of normal life. It is known that environmental factors may cause or contribute to the development of cancer. However, studies that are more detailed are needed to determine the exact cause of a health effect. As a result, when a large number of studies have been performed, association the actual risk of cancer with the environmental risk factors can be clearer.