early in progression to cancer and are a possible cause of the genetic instability characteristic of cancers. reduced expression of dna repair genes disrupts dna repair. this is shown in the figure at the 4th level from the top. (in the figure, red wording indicates the central role of dna damage and defects in dna repair in progression to cancer.) when dna repair is deficient dna damage remains in cells at a higher than usual level (5th level) and causes increased frequencies of mutation and/or epimutation (6th level). mutation rates increase substantially in cells defective in dna mismatch repair or in homologous recombinational repair (hrr). chromosomal rearrangements and aneuploidy also increase in hrr defective cells. higher levels of dna damage cause increased mutation (right side of figure) and increased epimutation. during repair of dna double strand breaks, or repair of other dna damage, incompletely cleared repair sites can cause epigenetic gene silencing. deficient expression of dna repair proteins due to an inherited mutation can increase cancer risks. individuals with an inherited impairment in any of 34 dna repair genes (see article dna repair-deficiency disorder) have increased cancer risk, with some defects ensuring a 100% lifetime chance of cancer (e.g. p53 mutations). germ line dna repair mutations are noted on the figure's left side. however, such germline mutations (which cause highly penetrant cancer syndromes) are the cause of only about 1 percent of cancers. in sporadic cancers, deficiencies in dna repair are occasionally caused by a mutation in a dna repair gene but are much more frequently caused by epigenetic alterations that reduce or silence expression of dna repair genes. this is indicated in the figure at the 3rd level. many studies of heavy metal-induced carcinogenesis show that such heavy metals cause a reduction in expression of dna repair enzymes, some through epigenetic mechanisms. dna repair inhibition is proposed to be a predominant mechanism in heavy metal-induced carcinogenicity. in addition, frequent epigenetic alterations of the dna sequences code for small rnas called micrornas (or mirnas). mirnas do not code for proteins, but can "target" protein-coding genes and reduce their expression. cancers usually arise from an assemblage of mutations and epimutations that confer a selective advantage leading to clonal expansion (see field defects in progression to cancer). mutations, however, may not be as frequent in cancers as epigenetic alterations. an average cancer of the breast or colon can have about 60 to 70 protein-altering mutations, of which about three or four may be "driver" mutations and the remaining ones may be "passenger" mutations. metastasis main article: metastasis metastasis is the spread of cancer to other locations in the body. the dispersed tumors are called metastatic tumors, while the original is called the primary tumor. almost all cancers can metastasize. most cancer deaths are due to cancer that has metastasized. metastasis is common in the late stages of cancer and it can occur via the blood or the lymphatic system or both. the typical steps in metastasis are local invasion, intravasation into the blood or lymph, circulation through the body, extravasation into the new tissue, proliferation and angiogenesis. different types of cancers tend to metastasize to particular organs, but overall the most common places for metastases to occur are the lungs, liver, brain and the bones. metabolism main article: tumor metabolome normal cells typically generate only about 30% of energy from glycolysis, whereas most cancers rely on glycolysis for energy production (warburg effect). but a minority of cancer types rely on oxidative phosphorylation as the primary energy source, including lymphoma, leukemia, and endometrial cancer. even in these cases, however, the use of glycolysis as an energy source rarely exceeds 60%. a few cancers use glutamine as the major energy source, partly because it provides nitrogen required for nucleotide (dna, rna) synthesis. cancer stem cells often use oxidative phosphorylation or glutamine as a primary energy source. several studies have indicated that the enzyme sirtuin 6 is selectively inactivated during oncogenesis in a variety of tumor types by inducing glycolysis. another sirtuin, sirtuin 3 inhibits cancers that depend upon glycolysis, but promotes cancers that depend upon oxidative phosphorylation. a low-carbohydrate diet (ketogenic diet) has sometimes been recommended as a supportive therapy for cancer treatment. diagnosis chest x-ray showing lung cancer in the left lung most cancers are initially recognized either because of the appearance of signs or symptoms or through screening. neither of these leads to a definitive diagnosis, which requires the examination of a tissue sample by a pathologist. people with suspected cancer are investigated with medical tests. these commonly include blood tests, x-rays, (contrast) ct scans and endoscopy. the tissue diagnosis from the biopsy indicates the type of cell that is proliferating, its histological grade, genetic abnormalities and other features. together, this information is useful to evaluate the prognosis and to choose the best treatment. cytogenetics and immunohistochemistry are other types of tissue tests. these tests provide information about molecular changes (such as mutations, fusion genes and numerical chromosome changes) and may thus also indicate the prognosis and best treatment. cancer diagnosis can cause psychological distress and psychosocial interventions, such as talking therapy, may help people with this. classification further information: list of cancer types and list of oncology-related terms cancers are classified by the type of cell that the tumor cells resemble and is therefore presumed to be the origin of the tumor. these types include: carcinoma: cancers derived from epithelial cells. this group includes many of the most common cancers and include nearly all those in the breast, prostate, lung, pancreas and colon. sarcoma: cancers arising from connective tissue (i.e. bone, cartilage, fat, nerve), each of which develops from cells originating in mesenchymal cells outside the bone marrow. lymphoma and leukemia: these two classes arise from hematopoietic (blood-forming) cells that leave the marrow and tend to mature in the lymph nodes and blood, respectively. germ cell tumor: cancers derived from pluripotent cells, most often presenting in the testicle or the ovary (seminoma and dysgerminoma, respectively). blastoma: cancers derived from immature "precursor" cells or embryonic tissue. cancers are usually named using -carcinoma, -sarcoma or -blastoma as a suffix, with the latin or greek word for the organ or tissue of origin as the root. for example, cancers of the liver parenchyma arising from malignant epithelial cells is called hepatocarcinoma, while a malignancy arising from primitive liver precursor cells is called a hepatoblastoma and a cancer arising from fat cells is called a liposarcoma. for some common cancers, the english organ name is used. for example, the most common type of breast cancer is called ductal carcinoma of the breast. here, the adjective ductal refers to the appearance of cancer under the microscope, which suggests that it has originated in the milk ducts. benign tumors (which are not cancers) are named using -oma as a suffix with the organ name as the root. for example, a benign tumor of smooth muscle cells is called a leiomyoma (the common name of this frequently occurring benign tumor in the uterus is fibroid). confusingly, some types of cancer use the -noma suffix, examples including melanoma and seminoma. some types of cancer are named for the size and shape of the cells under a microscope, such as giant cell carcinoma, spindle cell carcinoma and small-cell carcinoma. an invasive ductal carcinoma of the breast (pale area at the center) surrounded by spikes of whitish scar tissue and yellow fatty tissue an invasive colorectal carcinoma (top center) in a colectomy specimen a squamous-cell carcinoma (the whitish tumor) near the bronchi in a lung specimen a large invasive ductal carcinoma in a mastectomy specimen prevention global deaths from cancers attributable to risk factors in 2019 by sex and socio-demographic index. cancer dalys attributable to 11 level 2 risk factors globally in 2019. 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. further, poverty could be considered as an indirect risk factor in human cancers. 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. in 2019, ~44% of all cancer deaths – or ~4.5 m deaths or ~105 million lost disability-adjusted life years – were due to known clearly preventable risk factors, led by smoking, alcohol use and high bmi, according to a gbd systematic analysis. dietary main article: diet and cancer while many dietary recommendations have been proposed to reduce cancer risks, the evidence to support them is not definitive. the primary dietary factors that increase risk are obesity and alcohol consumption. diets low in fruits and vegetables and high in red meat have been implicated but reviews and meta-analyses do not come to a consistent conclusion. a 2014 meta-analysis found no relationship between fruits and vegetables and cancer. coffee is associated with a reduced risk of liver cancer. studies have linked excessive consumption of red or processed meat to an increased risk of breast cancer, colon cancer and pancreatic cancer, a phenomenon that could be due to the presence of carcinogens in meats cooked at high temperatures. in 2015 the iarc reported that eating processed meat (e.g., bacon, ham, hot dogs, sausages) and, to a lesser degree, red meat was linked to some cancers. dietary recommendations for cancer prevention typically include an emphasis on vegetables, fruit, whole grains and fish and an avoidance of processed and red meat (beef, pork, lamb), animal fats, pickled foods and refined carbohydrates. medication medications can be used to prevent cancer in a few circumstances. in the general population, nsaids reduce the risk of colorectal cancer; however, due to cardiovascular and gastrointestinal side effects, they cause overall harm when used for prevention. aspirin has been found to reduce the risk of death from cancer by about 7%. cox-2 inhibitors may decrease the rate of polyp formation in people with familial adenomatous polyposis; however, it is associated with the same adverse effects as nsaids. daily use of tamoxifen or raloxifene reduce the risk of breast cancer in high-risk women. the benefit versus harm for 5-alpha-reductase inhibitor such as finasteride is not clear. vitamin supplementation does not appear to be effective at preventing cancer. while low blood levels of vitamin d are correlated with increased cancer risk, whether this relationship is causal and vitamin d supplementation is protective is not determined. one 2014 review found that supplements had no significant effect on cancer risk. another 2014 review concluded that vitamin d3 may decrease the risk of death from cancer (one fewer death in 150 people treated over 5 years), but concerns with the quality of the data were noted. beta-carotene supplementation increases lung cancer rates in those who are high risk. folic acid supplementation is not effective in preventing colon cancer and may increase colon polyps. selenium supplementation has not been shown to reduce the risk of cancer. vaccination vaccines have been developed that prevent infection by some carcinogenic viruses. human papillomavirus vaccine (gardasil and cervarix) decrease the risk of developing cervical cancer. the hepatitis b vaccine prevents infection with hepatitis b virus and thus decreases the risk of liver cancer. the administration of human papillomavirus and hepatitis b vaccinations is recommended where resources allow. screening main article: cancer screening unlike diagnostic efforts prompted by symptoms and medical signs, cancer screening involves efforts to detect cancer after it has formed, but before any noticeable symptoms appear. this may involve physical examination, blood or urine tests or medical imaging. cancer screening is not available for many types of cancers. even when tests are available, they may not be recommended for everyone. universal screening or mass screening involves screening everyone. selective screening identifies people who are at higher risk, such as people with a family history. several factors are considered to determine whether the benefits of screening outweigh the risks and the costs of screening. these factors include: possible harms from the screening test: for example,