Tobacco smoking is by far the main contributor to lung cancer. Cigarette smoke contains at least 73 known carcinogens, including benzo["a"]pyrene, NNK, 1,3-butadiene and a radioactive isotope of polonium, polonium-210. Across the developed world, 90% of lung cancer deaths in men during the year 2000 were attributed to smoking (70% for women). Smoking accounts for about 85% of lung cancer cases.

Passive smoking—the inhalation of smoke from another's smoking—is a cause of lung cancer in nonsmokers. A passive smoker can be defined as someone living or working with a smoker. Studies from the US, Europe and the UK have consistently shown a significantly increased risk among those exposed to passive smoke. Those who live with someone who smokes have a 20–30% increase in risk while those who work in an environment with secondhand smoke have a 16–19% increase in risk. Investigations of sidestream smoke suggest it is more dangerous than direct smoke. Passive smoking causes about 3,400 deaths from lung cancer each year in the USA.

Marijuana smoke contains many of the same carcinogens as those in tobacco smoke. However, the effect of smoking cannabis on lung cancer risk is not clear. A 2013 review did not find an increased risk from light to moderate use. A 2014 review found that smoking cannabis doubled the risk of lung cancer.

Factors that contribute to the development of hypopharyngeal cancer include:

- Smoking

- Chewing tobacco

- Heavy alcohol use

- Poor diet

Smoking, like lung cancer, can cause hypopharyngeal cancer because it contains carcinogens that alter the DNA or RNA in a dividing cell. These alterations may change a normal DNA sequence to an oncogene, a gene that causes cancer after exposure to a carcinogen.

Squamous cells, a type of cell that lines hollow organs like the throat, mouth, lungs, and outer layer of skin, are particularly vulnerable when exposed to cigarette smoke.

Chewing tobacco can have the same effects as smoking and is also linked to hypopharyngeal cancer. The chewing tobacco is placed into the mouth, leaving it exposed to enzymes, like amylase, which partly digests the carcinogenic material. Saliva is swallowed, along with the cancer-promoting material, which passes through the hypopharynx on its way to the esophagus.

Heavy alcohol use is linked to Hypopharyngeal Cancer as well. Alcohol damages the lining of the hypopharynx, increasing the amount of chemicals that are allowed to seep into the underlying membranes. Heavy alcohol use is also associated with nutritional deficiencies.

A disease called Plummer-Vinson syndrome, a genetic disorder that causes a long-term iron deficiency, may also lead to Hypopharyngeal Cancer. Other factors like a deficiency in certain vitamins also appear to contribute to this type of cancer.

Adult survivors of childhood cancer have some physical, psychological, and social difficulties.

Premature heart disease is a major long-term complication in adult survivors of childhood cancer. Adult survivors are eight times more likely to die of heart disease than other people, and more than half of children treated for cancer develop some type of cardiac abnormality, although this may be asymptomatic or too mild to qualify for a clinical diagnosis of heart disease.

Outdoor air pollutants, especially chemicals released from the burning of fossil fuels, increase the risk of lung cancer. Fine particulates (PM) and sulfate aerosols, which may be released in traffic exhaust fumes, are associated with slightly increased risk. For nitrogen dioxide, an incremental increase of 10 parts per billion increases the risk of lung cancer by 14%. Outdoor air pollution is estimated to account for 1–2% of lung cancers.

Tentative evidence supports an increased risk of lung cancer from indoor air pollution related to the burning of wood, charcoal, dung or crop residue for cooking and heating. Women who are exposed to indoor coal smoke have about twice the risk and a number of the by-products of burning biomass are known or suspected carcinogens. This risk affects about 2.4 billion people globally, and is believed to account for 1.5% of lung cancer deaths.

Most people with cancer of unknown primary origin have widely disseminated and incurable disease, although a few can be cured through treatment. With treatment, typical survival with CUP ranges from 6 to 16 months. Survival rates are lower in cases with visceral metastatic disease, ranging from 6 to 9 months. Survival rates are higher when the cancer is more limited to lymph nodes, pleura, or peritoneal metastasis, which ranges from 14 to 16 months. Long-term prognosis is somewhat better if a particular source of cancer is strongly suggested by clinical evidence.

CUP sometimes runs in families. It has been associated with familial lung, kidney, and colorectal cancers, which suggests that these sites may often be the origin of unidentifiable CUP cancers.

Familial and genetic factors are identified in 5-15% of childhood cancer cases. In <5-10% of cases, there are known environmental exposures and exogenous factors, such as prenatal exposure to tobacco, X-rays, or certain medications. For the remaining 75-90% of cases, however, the individual causes remain unknown. In most cases, as in carcinogenesis in general, the cancers are assumed to involve multiple risk factors and variables.

Aspects that make the risk factors of childhood cancer different from those seen in adult cancers include:

- Different, and sometimes unique, exposures to environmental hazards. Children must often rely on adults to protect them from toxic environmental agents.

- Immature physiological systems to clear or metabolize environmental substances

- The growth and development of children in phases known as "developmental windows" result in certain "critical windows of vulnerability".

Also, a longer life expectancy in children avails for a longer time to manifest cancer processes with long latency periods, increasing the risk of developing some cancer types later in life.

There are preventable causes of childhood malignancy, such as delivery overuse and misuse of ionizing radiation through computed tomography scans when the test is not indicated or when adult protocols are used.

Malignant germ cell tumors of the mediastinum are uncommon, representing only 3 to 10% of tumors originating in the mediastinum. They are much less common than germ cell tumors arising in the testes, and account for only 1 to 5% of all germ cell neoplasms.

Syndromes associated with mediastinal germ cell tumors include Hematologic Neoplasia and Klinefelter's syndrome.

Current consensus is that the long-term prognosis of c-SCLC patients is determined by the SCLC component of their tumor, given that "pure" SCLC seems to have the worst long-term prognosis of all forms of lung cancer. Although data on c-SCLC is very sparse, some studies suggest that survival rates in c-SCLC may be even worse than that of pure SCLC, likely due to the lower rate of complete response to chemoradiation in c-SCLC, although not all studies have shown a significant difference in survival.

Untreated "pure" SCLC patients have a median survival time of between 4 weeks and 4 months, depending on stage and performance status at the time of diagnosis.

Given proper multimodality treatment, SCLC patients with limited disease have median survival rates of between 16 and 24 months, and about 20% will be cured. In patients with extensive disease SCLC, although 60% to 70% will have good-to-complete responses to treatment, very few will be cured, with a median survival of only 6 to 10 months.

Some evidence suggests that c-SCLC patients who continue to smoke may have much worse outcomes after treatment than those who quit.

Smoking tobacco appears to increase the risk of breast cancer, with the greater the amount smoked and the earlier in life that smoking began, the higher the risk. In those who are long-term smokers, the risk is increased 35% to 50%. A lack of physical activity has been linked to about 10% of cases. Sitting regularly for prolonged periods is associated with higher mortality from breast cancer. The risk is not negated by regular exercise, though it is lowered.

There is an association between use of hormonal birth control and the development of premenopausal breast cancer, but whether oral contraceptives use may actually cause premenopausal breast cancer is a matter of debate. If there is indeed a link, the absolute effect is small. Additionally, it is not clear if the association exists with newer hormonal birth controls. In those with mutations in the breast cancer susceptibility genes "BRCA1" or "BRCA2", or who have a family history of breast cancer, use of modern oral contraceptives does not appear to affect the risk of breast cancer.

The association between breast feeding and breast cancer has not been clearly determined; some studies have found support for an association while others have not. In the 1980s, the abortion–breast cancer hypothesis posited that induced abortion increased the risk of developing breast cancer. This hypothesis was the subject of extensive scientific inquiry, which concluded that neither miscarriages nor abortions are associated with a heightened risk for breast cancer.

A number of dietary factors have been linked to the risk for breast cancer. Dietary factors which may increase risk include a high fat diet, high alcohol intake, and obesity-related high cholesterol levels. Dietary iodine deficiency may also play a role. Evidence for fiber is unclear. A 2015 review found that studies trying to link fiber intake with breast cancer produced mixed results. In 2016 a tentative association between low fiber intake during adolescence and breast cancer was observed.

Other risk factors include radiation and shift-work. A number of chemicals have also been linked, including polychlorinated biphenyls, polycyclic aromatic hydrocarbons, and organic solvents Although the radiation from mammography is a low dose, it is estimated that yearly screening from 40 to 80 years of age will cause approximately 225 cases of fatal breast cancer per million women screened.

Working with asbestos is the most common risk factor for mesothelioma. However, mesothelioma has been reported in some individuals without any known exposure to asbestos.

People with HPV-mediated oropharyngeal cancer tend to have higher survival rates. The prognosis for people with oropharyngeal cancer depends on the age and health of the person and the stage of the disease. It is important for people with oropharyngeal cancer to have follow-up exams for the rest of their lives, as cancer can occur in nearby areas. In addition, it is important to eliminate risk factors such as smoking and drinking alcohol, which increase the risk for second cancers.

Reliable comprehensive incidence statistics for c-SCLC are unavailable. In the literature, the frequency with which the c-SCLC variant is diagnosed largely depends on the size of tumor samples, tending to be higher in series where large surgical resection specimens are examined, and lower when diagnoses are based on small cytology and/or biopsy samples. Tatematsu "et al." reported 15 cases of c-SCLC (12%) in their series of 122 consecutive SCLC patients, but only 20 resection specimens were examined. In contrast, Nicholson "et al." found 28 c-SCLC (28%) in a series of 100 consecutive resected SCLC cases. It appears likely, then, that the c-SCLC variant comprises 25% to 30% of all SCLC cases.

As the incidence of SCLC has declined somewhat in the U.S. in recent decades, it is likely that c-SCLC has also decreased in incidence. Nevertheless, small cell carcinomas (including the c-SCLC variant) still comprise 15–20% of all lung cancers, with c-SCLC probably accounting for 4–6%. With 220,000 cases of newly diagnosed lung cancer in the U.S. each year, it can be estimated that between 8,800 and 13,200 of these are c-SCLC.

In a study of 408 consecutive patients with SCLC, Quoix and colleagues found that presentation as a solitary pulmonary nodule (SPN) is particularly indicative of a c-SCLC — about 2/3 of their SPN's were pathologically confirmed to be c-SCLC's containing a large cell carcinoma component.

Cancer prevention is defined as active measures to decrease cancer risk. The vast majority of cancer cases are due to environmental risk factors. Many of these environmental factors are controllable lifestyle choices. Thus, cancer is generally preventable. Between 70% and 90% of common cancers are due to environmental factors and therefore potentially preventable.

Greater than 30% of cancer deaths could be prevented by avoiding risk factors including: tobacco, excess weight/obesity, poor diet, physical inactivity, alcohol, sexually transmitted infections and air pollution. Not all environmental causes are controllable, such as naturally occurring background radiation and cancers caused through hereditary genetic disorders and thus are not preventable via personal behavior.

Risk factors can be divided into two categories:

- "modifiable" risk factors (things that people can change themselves, such as consumption of alcoholic beverages), and

- "fixed" risk factors (things that cannot be changed, such as age and biological sex).

The primary risk factors for breast cancer are being female and older age. Other potential risk factors include genetics, lack of childbearing or lack of breastfeeding, higher levels of certain hormones, certain dietary patterns, and obesity. Recent studies have indicated that exposure to light pollution is a risk factor for the development of breast cancer.

The differential diagnosis of serous carcinoma not otherwise specified includes:

- Ovarian serous carcinoma, a type of ovarian cancer.

- Uterine serous carcinoma, also known as "uterine papillary serous carcinoma", a type of uterine cancer.

- Fallopian tube serous carcinoma, a type of uterine tube cancer.

- Cervical serous carcinoma, a rare type of cervical cancer.

- Primary peritoneal serous carcinoma, a very rare cancer that arise from the peritoneum.

There has been the suggestion that the above diagnoses really represent one entity.

Symptoms of Hypopharyngeal Cancer include:

- Swollen lymph nodes in the neck (first sign of a problem in half of all patients)

- Sore throat in one location that persists after treatment

- Pain that radiates from the throat to the ears

- Difficult or painful swallowing (often leads to malnutrition and weight loss because of a refusal to eat)

- Voice changes (late stage cancer)

Up to 10% of invasive cancers are related to radiation exposure, including both ionizing radiation and non-ionizing ultraviolet radiation. 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. Residential exposure to radon gas, for example, has similar cancer risks as passive smoking. Radiation is a more potent source of cancer when combined with other cancer-causing agents, such as radon plus tobacco smoke. 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.

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. It is also used in some kinds of medical imaging.

Prolonged exposure to ultraviolet radiation from the sun can lead to melanoma and other skin malignancies. 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.

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. However, studies have not found a consistent link between mobile phone radiation and cancer risk.

Mediastinal germ cell tumors are tumors that derive from germ cell rest remnants in the mediastinum. They most commonly occur in the gonad but occasionally elsewhere.

The risk factors that can increase the risk of developing oropharyngeal cancer are:

- Smoking and chewing tobacco

- Heavy alcohol use

- A diet low in fruits and vegetables

- Chewing betel quid, a stimulant commonly used in parts of Asia

- Mucosal infection with human papilloma virus (HPV) (HPV-mediated oropharyngeal cancer)

- HPV infection

- Plummer-Vinson syndrome

- Poor nutrition

- Asbestos exposure

Certain genetic changes including: P53 mutation and CDKN2A (p16) mutations.

High-risk lesions:

- Erythroplakia

- Speckled erythroplakia

- Chronic hyperplastic candidiasis

Medium-risk lesions:

- Oral submucosal fibrosis

- Syphilitic glossitis

- Sideropenic dysphagia (or Paterson-Kelly-Brown syndrome)

Low-risk lesions:

- Oral lichen planus

- Discoid lupus erythematosus

- Discoid keratosis congenita

Some therapies for other forms of cancer increase the lifetime risk of endometrial cancer, which is a baseline 2–3%. Tamoxifen, a drug used to treat estrogen-positive breast cancers, has been associated with endometrial cancer in approximately 0.1% of users, particularly older women, but the benefits for survival from tamoxifen generally outweigh the risk of endometrial cancer. A one to two-year course of tamoxifen approximately doubles the risk of endometrial cancer, and a five-year course of therapy quadruples that risk. Raloxifene, a similar drug, did not raise the risk of endometrial cancer. Previously having ovarian cancer is a risk factor for endometrial cancer, as is having had previous radiotherapy to the pelvis. Specifically, ovarian granulosa cell tumors and thecomas are tumors associated with endometrial cancer.

Low immune function has also been implicated in endometrial cancer. High blood pressure is also a risk factor, but this may be because of its association with obesity. Sitting regularly for prolonged periods is associated with higher mortality from endometrial cancer. The risk is not negated by regular exercise, though it is lowered.

Some studies in Australia, Brazil and Germany pointed to alcohol-containing mouthwashes as also being potential causes. The claim was that constant exposure to these alcohol-containing rinses, even in the absence of smoking and drinking, leads to significant increases in the development of oral cancer. However, studies conducted in 1985, 1995, and 2003 summarize that alcohol-containing mouth rinses are not associated with oral cancer. In a March 2009 brief, the American Dental Association said "the available evidence does not support a connection between oral cancer and alcohol-containing mouthrinse". A 2008 study suggests that acetaldehyde (a breakdown product of alcohol) is implicated in oral cancer, but this study specifically focused on abusers of alcohol and made no reference to mouthwash. Any connection between oral cancer and mouthwash is tenuous without further investigation.

Mesothelioma often has a poor prognosis. Typical survival despite surgery is between 12 and 21 months depending on the stage of disease at diagnosis with about 7.5% of people surviving for 5 years.

Women, young people, people with low-stage cancers, and people with epithelioid cancers have better prognoses. Negative prognostic factors include sarcomatoid or biphasic histology, high platelet counts (above 400,000), age over 50 years, white blood cell counts above 15.5, low glucose levels in the pleural fluid, low albumin levels, and high fibrinogen levels. Several markers are under investigation as prognostic factors, including nuclear grade, and serum c-reactive protein. Long-term survival is rare.

Pericardial mesothelioma has a 10-month median survival time.

In peritoneal mesothelioma, high expression of WT-1 protein indicates a worse prognosis.

In a study of Europeans, smoking and other tobacco use was associated with about 75 percent of oral cancer cases, caused by irritation of the mucous membranes of the mouth from smoke and heat of cigarettes, cigars, and pipes. Tobacco contains over 60 known carcinogens, and the combustion of it, and by-products from this process, is the primary mode of involvement. Use of chewing tobacco or snuff causes irritation from direct contact with the mucous membranes.

Tobacco use in any form by itself, and even more so in combination with heavy alcohol consumption, continues to be an important risk factor for oral cancer. However, due to the current trends in the spread of HPV16, as of early 2011 the virus is now considered the primary causative factor in 63% of newly diagnosed patients.

Smoking and the use of progestin are both protective against endometrial cancer. Smoking provides protection by altering the metabolism of estrogen and promoting weight loss and early menopause. This protective effect lasts long after smoking is stopped. Progestin is present in the combined oral contraceptive pill and the hormonal intrauterine device (IUD). Combined oral contraceptives reduce risk more the longer they are taken: by 56% after four years, 67% after eight years, and 72% after twelve years. This risk reduction continues for at least fifteen years after contraceptive use has been stopped. Obese women may need higher doses of progestin to be protected. Having had more than five infants (grand multiparity) is also a protective factor, and having at least one child reduces the risk by 35%. Breastfeeding for more than 18 months reduces risk by 23%. Increased physical activity reduces an individual's risk by 38–46%. There is preliminary evidence that consumption of soy is protective.