The etiology of tumors is very complex, often one carcinogen can induce multiple tumors, and one tumor may have multiple causes. Humans are usually exposed to a complex mixture of carcinogens rather than a single carcinogenic factor. This complexity makes the study of tumor etiology extremely challenging. Overall, to date, the etiology of most tumors is not fully understood. It is now generally accepted that the vast majority of tumors are caused by the interaction of environmental factors with the genetic material of the cells. The term “environmental factors” refers to such things as cigarettes, dietary components, environmental pollutants, drugs, radiation, and infectious agents (i.e., chemical, biological, and physical factors). Geographical differences in tumor distribution, migration epidemiology, animal carcinogenesis experiments, and in vitro malignant transformation of human cells all support environmental factors as the etiology of most tumors. However, with the same exposure to a specific environment, some individuals develop tumors while others survive beyond a normal life span, suggesting that individual self factors such as genetic characteristics, age, sex, immune and nutritional status play an important role in tumorigenesis. Since the 20th century, studies on epidemiology, high incidence areas and occupational cancers have provided a lot of reliable clues and bases for finding and determining the causes of tumors. (a) Smoking There have been many studies on the etiology of lung cancer. The relationship between smoking and lung cancer has been proven by a large number of facts. Smoking is a recognized cause of lung cancer, but the proportion of smokers who develop lung cancer is less than 20%. We will elaborate on this in the chapter on lung cancer. Smoking can cause not only lung cancer but is also associated with the development of oral, hypopharyngeal, esophageal, gastric, bladder, and cardiovascular diseases. Worryingly, according to a recent survey, the proportion of smoking among urban high school students in China is 30-40%. (ii) Radiation and ultraviolet light Exposure to ionizing radiation from nature or industrial, medical and other sources can cause various cancers, including leukemia, breast and thyroid cancers. Bone, hematopoietic system and lung are organs sensitive to radiation. Japanese atomic bomb victims developed leukemia in the acute phase; thyroid or lung cancer rates were increased among atomic bomb victims in the chronic phase and among patients who had previously been irradiated for arthritis in the spine. Sunlight is a major source of ultraviolet radiation, and long-term UV exposure can cause skin cancer, especially in highly exposed Caucasian populations. Very low frequency electromagnetic fields may also be associated with cancer, but it is not conclusive. (iii) Chemical carcinogens Many compounds are carcinogenic. For example, benzo(a)pyrene contained in cigarettes has a strong carcinogenic effect and can cause skin cancer and lung cancer. Aflatoxin produced by aflatoxin-contaminated food may cause liver cancer. Arsenic can cause skin cancer, lung cancer and liver cancer. Currently recognized chemical carcinogens are also asbestos, chromium, nickel, coal tar, mustard gas, mineral oil, dichloromethyl ether, and so on. The most important chemical carcinogens for the total human cancer risk are currently considered to be the many carcinogenic components of cigarettes. Other chemical carcinogens are mainly combustion and organic synthesis products, certain food components, microbial contamination products, or substances resulting from food preparation processes. In addition, certain physiological and pathological processes in the human body itself, such as inflammation, oxidative stress, nutritional and hormonal imbalances, and repeated tissue damage, can also produce carcinogenic chemicals such as oxygen radicals. It is estimated that chemical carcinogenic factors dominate among human cancers caused by environmental factors. （Although most tumors are not infectious, certain RNA viruses such as human T-cell leukemia virus-1 (HTLV-1) and HTLV-2 viruses are known to cause leukemia and lymphoma; certain DNA viruses such as hepatitis B virus (HBV) and hepatitis C virus (HCV), EBV, and high-risk human papillomavirus (HPV) can cause liver cancer, hepatitis B and hepatitis C cancer, respectively.) can cause liver cancer, Burkitt’s lymphoma, nasopharyngeal cancer, Hodgkin’s lymphoma, and cervical cancer, respectively. More recent data also suggest that Helicobacter pylori (H. pylori, Hp) is also carcinogenic and associated with the development of gastric lymphoma. At least eight viruses have now been shown to be associated with a number of tumors in humans, although the degree of certainty of their relevance varies. Other biologic factors that cause cancer include some bacteria and parasites. Information from 1995 estimates that biological factors cause 18% of all human tumors. (v) Chronic diseases Many data indicate that cancer is prone to develop on the basis of chronic scarring. For example, chronic inflammation of gastric mucosa caused by Helicobacter pylori infection is the basis for the occurrence of gastric cancer. Chronic ulcers in the skin that do not heal for a long time may become cancerous. In northwest China, skin cancer caused by hot bed burn scars is often called “bed cancer”, and there are many colorectal cancers in areas with high incidence of schistosomiasis, which may also be the result of chronic infection. (vi) Nutritional factors Nutrition and cancer are also closely related. It is estimated that 1/3 of all human cancers are caused by nutritional factors. It is undoubtedly necessary and beneficial to further determine the role of these factors in the long and complex development of human cancer. Vitamin A and its analogs (commonly known as vincristines) are associated with epithelial differentiation. In the absence of vincristine in food, the sensitivity of experimental animals to carcinogens is enhanced. The epithelial tissues of the skin, uterus, stomach, trachea, and bronchi of experimental animals are protected against chemical carcinogenesis if supplemented with natural vincristine. Vimentin can inhibit the cell transformation process of normal cells caused by radiation, chemical carcinogens or viruses, and can inhibit migratory cell carcinoma and squamous cell carcinoma induced by chemical carcinogens in rats. In tissue culture, the addition of vincristine can cause the disappearance of squamous metaplasia of epithelium and inhibit the growth of certain tumor cells. Further studies have demonstrated that vincristine can act as an antioxidant to directly inhibit the carcinogenic effect of some carcinogens and inhibit the binding of some carcinogens to DNA, and antagonize the effect of carcinogenic substances, thus directly interfering with the carcinogenic process. In addition, vincristine is essential for the control of normal differentiation and growth of many epithelial tissues, has a regulatory effect on gene expression, and has an effect on the body’s immune system. The results of large prospective population-based observations in New York and Chicago, USA, also indicate that the intake of natural vitamin A b-carotene in food is negatively associated with the development of several types of cancer over a decade later, most notably lung cancer. Another striking aspect is the relationship between colorectal cancer and fatty diets. Colorectal cancer has been the second most common tumor in Singapore for more than 30 years since the country was founded, which is especially worthy of our reference. It has been proved that excessive calories and obesity will lead to higher incidence of breast cancer, colorectal cancer and pancreatic cancer. (vii) Immunosuppression The incidence of cancer in patients who need to apply immunosuppression for a long time for organ transplantation is significantly higher than that of the general population. AIDS patients are prone to multiple angiosarcomas (Kaposi’s sarcoma) and lymphomas. The potential hazards of long-term immunosuppression for various diseases should be carefully weighed. (viii) Genetic factors Most human tumors are caused by environmental factors. However, the same exposure to specific carcinogens causes some individuals to develop but not others; in addition, some tumors have significant familial aggregation. These facts suggest that the occurrence of tumors is also related to individual genetic factors. It is currently believed that environmental factors are the initiating factors for tumorigenesis, while individual genetic characteristics determine tumor susceptibility. The hottest and most encouraging topic of cancer research in medicine and other biological sciences is currently genetic research. Genetic abnormalities associated with carcinogenesis include mutations or loss of oncogenes, or activation of oncogenes. The causes of these mutations are complex and include viral oncogene insertion, chemical and physical factors that cause mutations and structural damage to genes. Some of these alterations can be inherited, making carriers susceptible to cancer. To date, chromosomal abnormalities and genetic defects in cancers associated with genetic disorders have been largely elucidated. However, these genetic disorders associated with tumor susceptibility are very rare, and they cause only 5% to 10% of all cancers, and more than 90% of patients with common tumors do not have these genetic alterations. What are the genetic susceptibility factors for most common tumors? This question is still unclear. With the initial completion of the Human Genome Project, the relationship between single nucleotide polymorphisms and disease susceptibility has received widespread attention. The results of the Human Genome Project have demonstrated that 99.9% of genes are the same in different individuals, but there are very small (0.1%) genetic differences in sequence, mainly single nucleotide polymorphisms. A single nucleotide polymorphism is a nucleotide mutation that occurs at a frequency of ³1% in a population. It is this 0.1% genetic difference that confers on each individual a unique phenotype, differential susceptibility to disease (tumors) and response to treatment (chemotherapy and radiation therapy). It is important to elucidate the mechanisms of genetic susceptibility to tumors. The study of highly susceptible hereditary cancer syndromes has led to the identification of “oncogenic pathway” genes that are also commonly altered in non-inherited sporadic tumors, which has led to substantial insights into the mechanisms of tumorigenesis and progression. A number of genetic tests to predict the risk of specific tumors have become an important part of health care. Studies of gene-environment interactions and genetic variants outside of the oncogenic pathway and tumor susceptibility have contributed to a broader understanding of the processes involved in tumorigenesis and have helped to identify environmental risk factors and develop preventive measures for high-risk populations.