cancer

CANCER Cancer is a medical term: malignant neoplasm, is a class of

diseases in which a group of cells display uncontrolled growth (division beyond the normal limits), invasion (intrusion on and destruction of adjacent tissues), and sometimes metastasis (spread to other locations in the body via lymph or blood). These three malignant properties of cancers differentiate them from benign tumors, which are self-limited, and do not invade or metastasize. Most cancers form a tumor but some, like leukemia, do not. The branch of medicine concerned with the study, diagnosis, treatment, and prevention of cancer is oncology.

EPIDEMIOLOGY• as of 2004[update], worldwide cancer caused 13% of all deaths (7.4 million). The leading causes were: lung

cancer (1.3 million deaths/year), stomach cancer (803,000 deaths), colorectal cancer (639,000 deaths), liver cancer (610,000 deaths), and breast cancer (519,000 deaths).[86] Greater than 30% of cancer is preventable via avoiding risk factors including: tobacco, overweight or obesity, low fruit and vegetable intake, physical inactivity, alcohol, sexually transmitted infections, and air pollution.[33]

• In the United States, cancer is responsible for 25% of all deaths with 30% of these from lung cancer. The most commonly occurring cancer in men is prostate cancer (about 25% of new cases) and in women is breast cancer (also about 25%). Cancer can occur in children and adolescents, but it is uncommon (about 150 cases per million in the U.S.), with leukemia the most common.[87] In the first year of life the incidence is about 230 cases per million in the U.S., with the most common being neuroblastoma.[88]

• In the developed world, one in three people will develop cancer during their lifetimes. If all cancer patients survived and cancer occurred randomly, the lifetime odds of developing an second primary cancer would be one in nine.[89] However, cancer survivors have an increased risk of developing a second primary cancer, and the odds are about two in nine.[89] About half of these second primaries can be attributed to the normal one-in-nine risk associated with random chance.[89] The increased risk is believed to be primarily due to the same risk factors that produced the first cancer, such as the person's genetic profile, alcohol and tobacco use, obesity, and environmental exposures, and partly due, in some cases, to the treatment for the first cancer, which might have included mutagenic chemotherapeutic drugs or radiation.[89] Cancer survivors may also be more likely to comply with recommended screening, and thus may be more likely than average to detect cancers

PATHOLOGY

• A cancer may be suspected for a variety of reasons, but the definitive diagnosis of most malignancies must be confirmed by histological examination of the cancerous cells by a pathologist. Tissue can be obtained from a biopsy or surgery. Many biopsies (such as those of the skin, breast or liver) can be done in a doctor's office. Biopsies of other organs are performed under anesthesia and require surgery in an operating room.

• The tissue diagnosis given by the pathologist indicates the type of cell that is proliferating, its histological grade, genetic abnormalities, and other features of the tumor. Together, this information is useful to evaluate the prognosis of the patient and to choose the best treatment. Cytogenetics and immunohistochemistry are other types of testing that the pathologist may perform on the tissue specimen. These tests may provide information about the molecular changes (such as mutations, fusion genes, and numerical chromosome changes) that has happened in the cancer cells, and may thus also indicate the future behavior of the cancer (prognosis) and best treatment

A large invasive ductal carcinoma in a mastectomy specimen.

CANCER EFFECT

• Cancer affects people at all ages with the risk for most types increasing with age.Cancer caused about 13% of all human deaths in 2007 (7.6 million).

• Cancers are caused by abnormalities in the genetic material of the transformed cells. These abnormalities may be due to the effects of carcinogens, such as tobacco smoke, radiation, chemicals, or infectious agents. Other cancer-promoting genetic abnormalities may randomly occur through errors in DNA replication, or are inherited, and thus present in all cells from birth. The heritability of cancers is usually affected by complex interactions between carcinogens and the host's genome.

• Genetic abnormalities found in cancer typically affect two general classes of genes. Cancer-promoting oncogenes are typically activated in cancer cells, giving those cells new properties, such as hyperactive growth and division, protection against programmed cell death, loss of respect for normal tissue boundaries, and the ability to become established in diverse tissue environments. Tumor suppressor genes are then inactivated in cancer cells, resulting in the loss of normal functions in those cells, such as accurate DNA replication, control over the cell cycle, orientation and adhesion within tissues, and interaction with protective cells of the immune system.

CAUSES

• Cancer is a diverse class of diseases which differ widely in their causes and biology. Any organism, even plants, can acquire cancer. Nearly all known cancers arise gradually, as errors build up in the cancer cell and its progeny (see mechanisms section for common types of errors).

• Anything which replicates (our cells) will probabilistically suffer from errors (mutations). Unless error correction and prevention is properly carried out, the errors will survive, and might be passed along to daughter cells. Normally, the body safeguards against cancer via numerous methods, such as: apoptosis, helper molecules (some DNA polymerases), possibly senescence, etc. However these error-correction methods often fail in small ways, especially in environments that make errors more likely to arise and propagate. For example, such environments can include the presence of disruptive substances called carcinogens, or periodic injury (physical, heat, etc.), or environments that cells did not evolve to withstand, such as hypoxia (see subsections). Cancer is thus a progressive disease, and these progressive errors slowly accumulate until a cell begins to act contrary to its function in the organism.

THA ERROR WHICH CAUSE CANCER The errors which cause cancer are often self-amplifying, eventually compounding at an exponential rate.

For example:

* A mutation in the error-correcting machinery of a cell might cause that cell and its children to accumulate errors more rapidly

* A mutation in signaling (endocrine) machinery of the cell can send error-causing signals to nearby cells * A mutation might cause cells to become neoplastic, causing them to migrate and disrupt more healthy

cells * A mutation may cause the cell to become immortal (see telomeres), causing them to disrupt healthy cells

forever Thus cancer often explodes in something akin to a chain reaction caused by a few errors, which

compound into more severe errors. Errors which produce more errors are effectively the root cause of cancer, and also the reason that cancer is so hard to treat: even if there were 10,000,000,000 cancerous cells and one killed all but 10 of those cells, those cells (and other error-prone precancerous cells) could still self-replicate or send error-causing signals to other cells, starting the process over again. This rebellion-like scenario is an undesirable survival of the fittest, where the driving forces of evolution work against the body's design and enforcement of order. In fact, once cancer has begun to develop, this same force continues to drive the progression of cancer towards more invasive stages, and is called clonal evolution.

DIAGNOSIS

Definitive diagnosis requires the histologic examination of a biopsy specimen, although the initial indication of malignancy can be symptomatic or radiographic imaging abnormalities. Most cancers can be treated and some cured, depending on the specific type, location, and stage. Once diagnosed, cancer is usually treated with a combination of surgery, chemotherapy and radiotherapy. As research develops, treatments are becoming more specific for different varieties of cancer. There has been significant progress in the development of targeted therapy drugs that act specifically on detectable molecular abnormalities in certain tumors, and which minimize damage to normal cells. The prognosis of cancer patients is most influenced by the type of cancer, as well as the stage, or extent of the disease. In addition, histologic grading and the presence of specific molecular markers can also be useful in establishing prognosis, as well as in determining individual treatments.

PREVENTION Cancer prevention is defined as active measures to decrease the

incidence of cancer. Greater than 30% of cancer is preventable via avoiding risk factors

including: tobacco, overweight or obesity, low fruit and vegetable intake, physical inactivity, alcohol, sexually transmitted infection, air pollution.This can be accomplished by avoiding carcinogens or altering their metabolism, pursuing a lifestyle or diet that modifies cancer-causing factors and/or medical intervention (chemoprevention, treatment of pre-malignant lesions). The epidemiological concept of "prevention" is usually defined as either primary prevention, for people who have not been diagnosed with a particular disease, or secondary prevention, aimed at reducing recurrence or complications of a previously diagnosed illness.

DIET• The consensus on diet and cancer is that obesity increases the risk of developing cancer. Particular

dietary practices often explain differences in cancer incidence in different countries (e.g. gastric cancer is more common in Japan, while colon cancer is more common in the United States. In this example the preceding consideration of Haplogroups are excluded). Studies have shown that immigrants develop the risk of their new country, often within one generation, suggesting a substantial link between diet and cancer. Whether reducing obesity in a population also reduces cancer incidence is unknown.

• Despite frequent reports of particular substances (including foods) having a beneficial or detrimental effect on cancer risk, few of these have an established link to cancer. These reports are often based on studies in cultured cell media or animals. Public health recommendations cannot be made based on these studies until they have been validated in an observational (or occasionally a prospective interventional) trial in humans.

• Proposed dietary interventions for primary cancer risk reduction generally gain support from epidemiological association studies. Examples of such studies include reports that reduced meat consumption is associated with decreased risk of colon cancer, and reports that consumption of coffee is associated with a reduced risk of liver cancer. Studies have linked consumption of grilled meat to an increased risk of stomach cancer, colon cancer, breast cancer and pancreatic cancer, a phenomenon which could be due to the presence of carcinogens such as benzopyrene in foods cooked at high temperatures.

STUDIES OF DIET• A 2005 secondary prevention study showed that consumption of a plant-

based diet and lifestyle changes resulted in a reduction in cancer markers in a group of men with prostate cancer who were using no conventional treatments at the time. These results were amplified by a 2006 study. Over 2,400 women were studied, half randomly assigned to a normal diet, the other half assigned to a diet containing less than 20% calories from fat. The women on the low fat diet were found to have a markedly lower risk of breast cancer recurrence, in the interim report of December, 2006.

• Recent studies have also demonstrated potential links between some forms of cancer and high consumption of refined sugars and other simple carbohydrates. Although the degree of correlation and the degree of causality is still debated, some organizations have in fact begun to recommend reducing intake of refined sugars and starches as part of their cancer prevention regimens.

STUDIES OF DIET• In November 2007, the American Institute for Cancer Research (AICR), in conjunction with the World

Cancer Research Fund (WCRF), published Food, Nutrition, Physical Activity and the Prevention of Cancer: a Global Perspective, "the most current and comprehensive analysis of the literature on diet, physical activity and cancer". The WCRF/AICR Expert Report lists 10 recommendations that people can follow to help reduce their risk of developing cancer, including the following dietary guidelines: (1) reducing intake of foods and drinks that promote weight gain, namely energy-dense foods and sugary drinks, (2) eating mostly foods of plant origin, (3) limiting intake of red meat and avoiding processed meat, (4) limiting consumption of alcoholic beverages, and (5) reducing intake of salt and avoiding mouldy cereals (grains) or pulses (legumes).

• Some mushrooms offer an anti-cancer effect, which is thought to be linked to their ability to up-regulate the immune system. Some mushrooms known for this effect include, Reishi, Agaricus blazei,Maitake,and Trametes versicolor. Research suggests the compounds in medicinal mushrooms most responsible for up-regulating the immune system and providing an anti-cancer effect, are a diverse collection of polysaccharide compounds, particularly beta-glucans. Beta-glucans are known as "biological response modifiers", and their ability to activate the immune system is well documented. Specifically, beta-glucans stimulate the innate branch of the immune system. Research has shown beta-glucans have the ability to stimulate macrophage, NK cells, T cells, and immune system cytokines. The mechanisms in which beta-glucans stimulate the immune system is only partially understood. One mechanism in which beta-glucans are able to activate the immune system, is by interacting with the Macrophage-1 antigen (CD18) receptor on immune cells

VITAMINS

• Vitamin supplementation has not been proven effective in the prevention of cancer. The components of food are also proving to be more numerous and varied than previously understood, so patients are increasingly advised to consume fruits and vegetables for maximal health benefits.

• Vitamin D Low levels of vitamin D is correlated with increased cancer risk.Whether this relationship is causal is yet to be determined.

• Beta carotene Beta-carotene supplementation has been found to increase slightly, but not significantly risks of lung cancer.

• Folic acid Folic acid supplementation has not been found effective in preventing colon cancer and may increase colon polyps