Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body.[2][8] Not all tumors are cancerous; benign tumors do not spread to other parts of the body.[8] Possible signs and symptoms include a lump, abnormal bleeding, prolonged cough, unexplained weight loss and a change in bowel movements.[1] While these symptoms may indicate cancer, they may have other causes.[1] Over 100 types of cancers affect humans.[8]
Tobacco use is the cause of about 22% of cancer deaths.[2] Another 10% is due to obesity, poor diet, lack of physical activity, and excessive drinking of alcohol.[2][9][10] Other factors include certain infections, exposure to ionizing radiation and environmental pollutants.[3] In the developing world nearly 20% of cancers are due to infections such as hepatitis B, hepatitis C and human papillomavirus (HPV).[2] These factors act, at least partly, by changing the genes of a cell.[11] Typically many genetic changes are required before cancer develops.[11] Approximately 5–10% of cancers are due to inherited genetic defects from a person’s parents.[12] Cancer can be detected by certain signs and symptoms or screening tests.[2] It is then typically further investigated by medical imaging and confirmed by biopsy.[13]
Many cancers can be prevented by not smoking, maintaining a healthy weight, not drinking too much alcohol, eating plenty of vegetables, fruits and whole grains, vaccination against certain infectious diseases, not eating too much processed and red meat, and avoiding too much sunlight exposure.[14][15] Early detection through screening is useful for cervical and colorectal cancer.[16] The benefits of screening in breast cancer are controversial.[16][17] Cancer is often treated with some combination of radiation therapy, surgery, chemotherapy, and targeted therapy.[2][4] Pain and symptom management are an important part of care. Palliative care is particularly important in people with advanced disease.[2] The chance of survival depends on the type of cancer and extent of disease at the start of treatment.[11] In children under 15 at diagnosis the five-year survival rate in the developed world is on average 80%.[18] For cancer in the United States the average five-year survival rate is 66%.[5]
In 2015 about 90.5 million people had cancer.[6] About 14.1 million new cases occur a year (not including skin cancer other than melanoma).[11] It caused about 8.8 million deaths (15.7%) of human deaths.[7] The most common types of cancer in males are lung cancer, prostate cancer, colorectal cancer and stomach cancer. In females, the most common types are breast cancer, colorectal cancer, lung cancer and cervical cancer.[11] If skin cancer other than melanoma were included in total new cancers each year it would account for around 40% of cases.[19][20] In children, acute lymphoblastic leukaemia and brain tumors are most common except in Africa where non-Hodgkin lymphoma occurs more often.[18] In 2012, about 165,000 children under 15 years of age were diagnosed with cancer. The risk of cancer increases significantly with age and many cancers occur more commonly in developed countries.[11] Rates are increasing as more people live to an old age and as lifestyle changes occur in the developing world.[21] The financial costs of cancer were estimated at $1.16 trillion US dollars per year as of 2010.
Main article: Cancer signs and symptoms
Symptoms of cancer metastasis depend on the location of the tumor.
When cancer begins, it produces no symptoms. Signs and symptoms appear as the mass grows or ulcerates. The findings that result depend on the cancer’s type and location. Few symptoms are specific. Many frequently occur in individuals who have other conditions. Cancer is a “great imitator”. Thus, it is common for people diagnosed with cancer to have been treated for other diseases, which were hypothesized to be causing their symptoms.[28]
People may become anxious or depressed post-diagnosis. The risk of suicide in people with cancer is approximately double.[29]
Local symptoms
Local symptoms may occur due to the mass of the tumor or its ulceration. For example, mass effects from lung cancer can block the bronchus resulting in cough or pneumonia; esophageal cancer can cause narrowing of the esophagus, making it difficult or painful to swallow; and colorectal cancer may lead to narrowing or blockages in the bowel, affecting bowel habits. Masses in breasts or testicles may produce observable lumps. Ulceration can cause bleeding that, if it occurs in the lung, will lead to coughing up blood, in the bowels to anemia or rectal bleeding, in the bladder to blood in the urine and in the uterus to vaginal bleeding. Although localized pain may occur in advanced cancer, the initial swelling is usually painless. Some cancers can cause a buildup of fluid within the chest or abdomen.[28]
Systemic symptoms
General symptoms occur due to effects that are not related to direct or metastatic spread. These may include: unintentional weight loss, fever, excessive fatigue and changes to the skin.[30] Hodgkin disease, leukemias and cancers of the liver or kidney can cause a persistent fever.[28]
Some cancers may cause specific groups of systemic symptoms, termed paraneoplastic phenomena. Examples include the appearance of myasthenia gravis in thymoma and clubbing in lung cancer.[28]
Metastasis
Main article: Metastasis
Cancer can spread from its original site by local spread, lymphatic spread to regional lymph nodes or by hematogenous spread via the blood to distant sites, known as metastasis. When cancer spreads by a hematogenous route, it usually spreads all over the body. However, cancer ‘seeds’ grow in certain selected site only (‘soil’) as hypothesized in the soil and seed hypothesis of cancer metastasis. The symptoms of metastatic cancers depend on the tumor location and can include enlarged lymph nodes (which can be felt or sometimes seen under the skin and are typically hard), enlarged liver or enlarged spleen, which can be felt in the abdomen, pain or fracture of affected bones and neurological symptoms.
Main article: Causes of cancer
The majority of cancers, some 90–95% of cases, are due to environmental factors. The remaining 5–10% are due to inherited genetics.[3] Environmental, as used by cancer researchers, means any cause that is not inherited genetically, such as lifestyle, economic and behavioral factors and not merely pollution.[31] Common environmental factors that contribute to cancer death include tobacco (25–30%), diet and obesity (30–35%), infections (15–20%), radiation (both ionizing and non-ionizing, up to 10%), stress, lack of physical activity and environmental pollutants.[3]
It is not generally possible to prove what caused a particular cancer because the various causes do not have specific fingerprints. For example, if a person who uses tobacco heavily develops lung cancer, then it was probably caused by the tobacco use, but since everyone has a small chance of developing lung cancer as a result of air pollution or radiation, the cancer may have developed for one of those reasons. Excepting the rare transmissions that occur with pregnancies and occasional organ donors, cancer is generally not a transmissible disease.[32]
Chemicals
Further information: Alcohol and cancer and Smoking and cancer
The incidence of lung cancer is highly correlated with smoking.
Exposure to particular substances have been linked to specific types of cancer. These substances are called carcinogens.
Tobacco smoke, for example, causes 90% of lung cancer.[33] It also causes cancer in the larynx, head, neck, stomach, bladder, kidney, esophagus and pancreas.[34] Tobacco smoke contains over fifty known carcinogens, including nitrosamines and polycyclic aromatic hydrocarbons.[35]
Tobacco is responsible for about one in five cancer deaths worldwide[35] and about one in three in the developed world.[36] Lung cancer death rates in the United States have mirrored smoking patterns, with increases in smoking followed by dramatic increases in lung cancer death rates and, more recently, decreases in smoking rates since the 1950s followed by decreases in lung cancer death rates in men since 1990.[37][38]
In Western Europe, 10% of cancers in males and 3% of cancers in females are attributed to alcohol exposure, especially liver and digestive tract cancers.[39] Cancer from work-related substance exposures may cause between 2 and 20% of cases,[40] causing at least 200,000 deaths.[41] Cancers such as lung cancer and mesothelioma can come from inhaling tobacco smoke or asbestos fibers, or leukemia from exposure to benzene.[41]
Diet and exercise
Main article: Diet and cancer
Diet, physical inactivity and obesity are related to up to 30–35% of cancer deaths.[3][42] In the United States excess body weight is associated with the development of many types of cancer and is a factor in 14–20% of cancer deaths.[42] A UK study including data on over 5 million people showed higher body mass index to be related to at least 10 types of cancer and responsible for around 12,000 cases each year in that country.[43] Physical inactivity is believed to contribute to cancer risk, not only through its effect on body weight but also through negative effects on the immune system and endocrine system.[42] More than half of the effect from diet is due to overnutrition (eating too much), rather than from eating too few vegetables or other healthful foods.
Some specific foods are linked to specific cancers. A high-salt diet is linked to gastric cancer.[44] Aflatoxin B1, a frequent food contaminant, causes liver cancer.[44] Betel nut chewing can cause oral cancer.[44] National differences in dietary practices may partly explain differences in cancer incidence. For example, gastric cancer is more common in Japan due to its high-salt diet[45] while colon cancer is more common in the United States. Immigrant cancer profiles develop mirror that of their new country, often within one generation.[46]
Infection
Main article: Infectious causes of cancer
Worldwide approximately 18% of cancer deaths are related to infectious diseases.[3] This proportion ranges from a high of 25% in Africa to less than 10% in the developed world.[3] Viruses are the usual infectious agents that cause cancer but cancer bacteria and parasites may also play a role.
Oncoviruses (viruses that can cause cancer) include human papillomavirus (cervical cancer), Epstein–Barr virus (B-cell lymphoproliferative disease and nasopharyngeal carcinoma), Kaposi’s sarcoma herpesvirus (Kaposi’s sarcoma and primary effusion lymphomas), hepatitis B and hepatitis C viruses (hepatocellular carcinoma) and human T-cell leukemia virus-1 (T-cell leukemias). Bacterial infection may also increase the risk of cancer, as seen in Helicobacter pylori-induced gastric carcinoma.[47][48] Parasitic infections associated with cancer include Schistosoma haematobium (squamous cell carcinoma of the bladder) and the liver flukes, Opisthorchis viverrini and Clonorchis sinensis (cholangiocarcinoma).[49]
Radiation
Main article: Radiation-induced cancer
Up to 10% of invasive cancers are related to radiation exposure, including both ionizing radiation and non-ionizing ultraviolet radiation.[3] Additionally, the majority of non-invasive cancers are non-melanoma skin cancers caused by non-ionizing ultraviolet radiation, mostly from sunlight. Sources of ionizing radiation include medical imaging and radon gas.
Ionizing radiation is not a particularly strong mutagen.[50] Residential exposure to radon gas, for example, has similar cancer risks as passive smoking.[50] Radiation is a more potent source of cancer when combined with other cancer-causing agents, such as radon plus tobacco smoke.[50] Radiation can cause cancer in most parts of the body, in all animals and at any age. Children and adolescents are twice as likely to develop radiation-induced leukemia as adults; radiation exposure before birth has ten times the effect.[50]
Medical use of ionizing radiation is a small but growing source of radiation-induced cancers. Ionizing radiation may be used to treat other cancers, but this may, in some cases, induce a second form of cancer.[50] It is also used in some kinds of medical imaging.[51]
Prolonged exposure to ultraviolet radiation from the sun can lead to melanoma and other skin malignancies.[52] Clear evidence establishes ultraviolet radiation, especially the non-ionizing medium wave UVB, as the cause of most non-melanoma skin cancers, which are the most common forms of cancer in the world.[52]
Non-ionizing radio frequency radiation from mobile phones, electric power transmission and other similar sources have been described as a possible carcinogen by the World Health Organization’s International Agency for Research on Cancer.[53] However, studies have not found a consistent link between mobile phone radiation and cancer risk.[54]
Heredity
Main article: Cancer syndrome
The vast majority of cancers are non-hereditary (sporadic). Hereditary cancers are primarily caused by an inherited genetic defect. Less than 0.3% of the population are carriers of a genetic mutation that has a large effect on cancer risk and these cause less than 3–10% of cancer.[55] Some of these syndromes include: certain inherited mutations in the genes BRCA1 and BRCA2 with a more than 75% risk of breast cancer and ovarian cancer,[55] and hereditary nonpolyposis colorectal cancer (HNPCC or Lynch syndrome), which is present in about 3% of people with colorectal cancer,[56] among others.
Physical agents
Some substances cause cancer primarily through their physical, rather than chemical, effects.[57] A prominent example of this is prolonged exposure to asbestos, naturally occurring mineral fibers that are a major cause of mesothelioma (cancer of the serous membrane) usually the serous membrane surrounding the lungs.[57] Other substances in this category, including both naturally occurring and synthetic asbestos-like fibers, such as wollastonite, attapulgite, glass wool and rock wool, are believed to have similar effects.[57] Non-fibrous particulate materials that cause cancer include powdered metallic cobalt and nickel and crystalline silica (quartz, cristobalite and tridymite).[57] Usually, physical carcinogens must get inside the body (such as through inhalation) and require years of exposure to produce cancer.[57]
Physical trauma resulting in cancer is relatively rare.[58] Claims that breaking bones resulted in bone cancer, for example, have not been proven.[58] Similarly, physical trauma is not accepted as a cause for cervical cancer, breast cancer or brain cancer.[58] One accepted source is frequent, long-term application of hot objects to the body. It is possible that repeated burns on the same part of the body, such as those produced by kanger and kairo heaters (charcoal hand warmers), may produce skin cancer, especially if carcinogenic chemicals are also present.[58] Frequent consumption of scalding hot tea may produce esophageal cancer.[58] Generally, it is believed that cancer arises, or a pre-existing cancer is encouraged, during the process of healing, rather than directly by the trauma.[58] However, repeated injuries to the same tissues might promote excessive cell proliferation, which could then increase the odds of a cancerous mutation.
Chronic inflammation has been hypothesized to directly cause mutation.[58][59] Inflammation can contribute to proliferation, survival, angiogenesis and migration of cancer cells by influencing the tumor microenvironment.[60][61] Oncogenes build up an inflammatory pro-tumorigenic microenvironment.[62]
Hormones
Some hormones play a role in the development of cancer by promoting cell proliferation.[63] Insulin-like growth factors and their binding proteins play a key role in cancer cell proliferation, differentiation and apoptosis, suggesting possible involvement in carcinogenesis.[64]
Hormones are important agents in sex-related cancers, such as cancer of the breast, endometrium, prostate, ovary and testis and also of thyroid cancer and bone cancer.[63] For example, the daughters of women who have breast cancer have significantly higher levels of estrogen and progesterone than the daughters of women without breast cancer. These higher hormone levels may explain their higher risk of breast cancer, even in the absence of a breast-cancer gene.[63] Similarly, men of African ancestry have significantly higher levels of testosterone than men of European ancestry and have a correspondingly higher level of prostate cancer.[63] Men of Asian ancestry, with the lowest levels of testosterone-activating androstanediol glucuronide, have the lowest levels of prostate cancer.[63]
Other factors are relevant: obese people have higher levels of some hormones associated with cancer and a higher rate of those cancers.[63] Women who take hormone replacement therapy have a higher risk of developing cancers associated with those hormones.[63] On the other hand, people who exercise far more than average have lower levels of these hormones and lower risk of cancer.[63] Osteosarcoma may be promoted by growth hormones.[63] Some treatments and prevention approaches leverage this cause by artificially reducing hormone levels and thus discouraging hormone-sensitive cancers.[63]
Autoimmune diseases
There is an association between celiac disease and an increased risk of all cancers. People with untreated celiac disease have a higher risk, but this risk decreases with time after diagnosis and strict treatment, probably due to the adoption of a gluten-free diet, which seems to have a protective role against development of malignancy in people with celiac disease. However, the delay in diagnosis and initiation of a gluten-free diet seems to increase the risk of malignancies.[65] Rates of gastrointestinal cancers are increased in people with Crohn’s disease and ulcerative colitis, due to chronic inflammation. Also, immunomodulators and biologic agents used to treat these diseases may promote developing extra-intestinal malignancies.
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