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 be 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. Tumour 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.

Definitive diagnosis requires the histological 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 tumours, 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, histological grading and the presence of specific molecular markers can also be useful in establishing prognosis, as well as in determining individual treatments.

Classification

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Cancers are classified by the type of cell that resembles the tumour and, therefore, the tissue presumed to be the origin of the tumour. These are the histology and the location, respectively. Examples of general categories include:

Carcinoma: Malignant tumours derived from epithelial cells. This group represents the most common cancers, including the common forms of breast, prostate, lung and colon cancer.

Sarcoma:Malignant tumours derived from connective tissue, or mesenchymal cells.

Lymphoma and leukemia: Malignancies derived from hematopoietic (blood-forming) cells

Germ cell tumour: Tumours derived from tot potent cells. In adults most often found in the testicle and ovary; in foetuses, babies, and young children most often found on the body midline, particularly at the tip of the tailbone; in horses most often found at the poll (base of the skull).

Blastic tumour or blastoma: A tumour (usually malignant) which resembles an immature or embryonic tissue. Many of these tumours are most common in children.

Malignant tumours (cancers) are usually named using -carcinoma, -sarcoma or -blastoma as a suffix, with the Latin or Greek word for the organ of origin as the root. For instance, a cancer of the liver is called hepatocarcinoma; a cancer of the fat cells is called liposarcoma. For common cancers, the English organ name is used. For instance, the most common type of breast cancer is called ductal carcinoma of the breast or mammary ductal carcinoma. Here, the adjective ductal refers to the appearance of the cancer under the microscope, resembling normal breast ducts.

Benign tumours (which are not cancers) are named using -oma as a suffix with the organ name as the root. For instance, a benign tumour of the smooth muscle of the uterus is called leiomyoma (the common name of this frequent tumour is fibroid). Unfortunately, some cancers also use the -oma suffix, examples being melanoma and semiformal.

Signs and Symptoms

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Symptoms of cancer metastasis depend on the location of the tumour; they vary based on the type of cancer. As cancer progresses to an advanced stage, common symptoms can include weight loss, fever, and fatigue. These are very non-specific symptoms that are more likely related to other less serious illnesses than cancer. Roughly, cancer symptoms can be divided into three groups:

Local symptoms: unusual lumps or swelling (tumour), haemorrhage (bleeding), pain and/or ulceration. Compression of surrounding tissues may cause symptoms such as jaundice (yellowing the eyes and skin).

Symptoms of metastasis (spreading): enlarged lymph nodes, cough and haemoptysis, hepatomegaly (enlarged liver), bone pain, fracture of affected bones and neurological symptoms. Although advanced cancer may cause pain, it is often not the first symptom.

• Systemic symptoms: weight loss, poor appetite, fatigue and cachexia (wasting), excessive sweating (night sweats), anaemia and specific paraneoplastic phenomena, i.e. specific conditions that are due to an active cancer, such as thrombosis or hormonal changes.

Every symptom in the above list can be caused by a variety of conditions. Cancer may be a common or uncommon cause of each item.

If you experience any of these signs, you should consult your Doctor. Some of these signs necessarily do not indicate the cancer disease. They may be due to reasons other than cancer. It is advisable to get screened every year to detect any cancer at an early stage. Cancers detected early can be cured.

Heavy wrinkling & cancer risk

The wrinkles you have may be an indication of your lung cancer risk, according to study by British researchers at The Royal Devon and Exeter Hospital (2006).

The studies have concluded that middle-aged smokers with heavily lined faces have a 5 times higher risk of lung disease than their unwrinkled peers. After age and the number of years someone had smoked were taken into account, heavy wrinkling was the next factor that seems to point to increased risk, they said.

Severe wrinkling also shows a lack of anti-ageing antioxidants, like vitamin C, which also help protect against disease. Medical experts are now recommending looking out for premature heavy wrinkling in addition to other symptoms of lung disease such as persistent smokers cough and breathlessness.

Causes

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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 animal.

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 signalling (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 itself 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. Research about cancer causes often falls into the following categories:

Agents (e.g. viruses) and events (e.g. mutations) which cause or facilitate genetic changes in cells destined to become cancer.

The precise nature of the genetic damage, and the genes which are affected by it.

The consequences of those genetic changes on the biology of the cell, both in generating the defining properties of a cancer cell, and in facilitating additional genetic events which lead to further progression of the cancer.

Other causes

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Excepting the rare transmissions that occur with pregnancies and only a marginal few organ donors, cancer is generally not a transmissible disease. The main reason for this is tissue graft rejection caused by MHC incompatibility. In humans and other vertebrates, the immune system uses MHC antigens to differentiate between "self" and "non-self" cells because these antigens are different from person to person. When non-self antigens are encountered, the immune system reacts against the appropriate cell. Such reactions may protect against tumour cell engraftment by eliminating implanted cells. In the United States, approximately 3,500 pregnant women have a malignancy annually, and transplacental transmission of acute leukaemia, lymphoma, melanoma and carcinoma from mother to foetus has been observed. The development of donor-derived tumours from organ transplants is exceedingly rare. The main cause of organ transplant associated tumours seems to be malignant melanoma that was undetected at the time of organ harvest, though other cases exist. In fact, cancer from one organism will usually grow in another organism of that species, as long as they share the same histocompatibility genes, proven using mice; however this would never happen in a real-world setting except as described above.

In non-humans, a few types of cancer have been found to be caused by transmission of the tumour cells themselves. This phenomenon is seen in dogs with Sticker's sarcoma, also known as canine transmissible venereal tumour, as well as Devil facial tumour disease in Tasmanian devils.

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.

Modifiable ("lifestyle") risk factors

The vast majority of cancer risk factors are environmental or lifestyle-related in nature, leading to the claim that cancer is a largely preventable disease. Examples of modifiable cancer risk factors include alcohol consumption (associated with increased risk of oral, oesophageal, breast, and other cancers), smoking (although 20% of women with lung cancer have never smoked, versus 10% of men, physical inactivity (associated with increased risk of colon, breast, and possibly other cancers), and being overweight / obese (associated with colon, breast, endometrial, and possibly other cancers). Based on epidemiologic evidence, it is now thought that avoiding excessive alcohol consumption may contribute to reductions in risk of certain cancers; however, compared with tobacco exposure, the magnitude of effect is modest or small and the strength of evidence is often weaker. Other lifestyle and environmental factors known to affect cancer risk (either beneficially or detrimentally) include certain sexually transmitted diseases (such as those conveyed by the human papillomavirus), the use of exogenous hormones, exposure to ionizing radiation and ultraviolet radiation, and certain occupational and chemical exposures.

Every year, at least 200,000 people die worldwide from cancer related to their workplace. Millions of workers run the risk of developing cancers such as lung cancer and mesothelioma from inhaling asbestos fibers and tobacco smoke, or leukemia from exposure to benzene at their workplaces.Currently, most cancer deaths caused by occupational risk factors occur in the developed world. It is estimated that approximately 20,000 cancer deaths and 40,000 new cases of cancer each year in the U.S. are attributable to occupation.

Diet

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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, a 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 on the basis of 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.

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 in which 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. 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 are 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

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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 being advised to consume fruits and vegetables for maximal health benefits.

Vitamin D

Low levels of vitamin D are 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.

Chemoprevention

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The concept that medications could be used to prevent cancer is an attractive one, and many high-quality clinical trials support the use of such chemoprevention in defined circumstances.

Daily use of tamoxifen, a selective estrogen receptor modulator (SERM), typically for 5 years, has been demonstrated to reduce the risk of developing breast cancer in high-risk women by about 50%. A recent study reported that the selective estrogen receptor modulator raloxifene has similar benefits to tamoxifen in preventing breast cancer in high-risk women, with a more favorable side effect profile. Raloxifene is a SERM like tamoxifen; it has been shown (in the STAR trial) to reduce the risk of breast cancer in high-risk women equally as well as tamoxifen. In this trial, which studied almost 20,000 women, raloxifene had fewer side effects than tamoxifen, though it did permit more DCIS to form. Finasteride, a 5-alpha-reductase inhibitor, has been shown to lower the risk of prostate cancer, though it seems to mostly prevent low-grade tumours. The effects of COX-2 inhibitors such as rofecoxib and celecoxib upon the risk of colon polyps have been studied in familial adenomatous polyposis patients and in the general population. In both groups, there were significant reductions in colon polyp incidence, but this came at the price of increased cardiovascular toxicity.

Genetic testing

Genetic testing for high-risk individuals is already available for certain cancer-related genetic mutations. Carriers of genetic mutations that increase risk for cancer incidence can undergo enhanced surveillance, chemoprevention, or risk-reducing surgery. Early identification of inherited genetic risk for cancer, along with cancer-preventing interventions such as surgery or enhanced surveillance, can be lifesaving for high-risk individuals.

Gene

Cancer types

Availability

BRCA1, BRCA2

Breast, ovarian, pancreatic

Commercially available for clinical specimens

MLH1, MSH2, MSH6, PMS1, PMS2

Colon, uterine, small bowel, stomach, urinary tract

Commercially available for clinical specimens

Vaccination

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Prophylactic vaccines have been developed to prevent infection by oncogenic infectious agents such as viruses, and therapeutic vaccines are in development to stimulate an immune response against cancer-specific epitopes.

As reported above, a preventive human papilloma virus vaccine exists that targets certain sexually transmitted strains of human papillomavirus that are associated with the development of cervical cancer and genital warts. The only two HPV vaccines on the market as of October 2007 are Gardasil and Cervarix. There is also a hepatitis B vaccine, which prevents infection with the hepatitis B virus, an infectious agent that can cause liver cancer. A canine melanoma vaccine has also been developed.

Screening

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Cancer screening is an attempt to detect unsuspected cancers in an asymptomatic population. Screening tests suitable for large numbers of healthy people must be relatively affordable, safe, noninvasive procedures with acceptably low rates of false positive results. If signs of cancer are detected, more definitive and invasive follow up tests are performed to confirm the diagnosis.

Screening for cancer can lead to earlier diagnosis in specific cases. Early diagnosis may lead to extended life, but may also falsely prolong the lead time to death through lead time bias or length time bias.

A number of different screening tests have been developed for different malignancies. Breast cancer screening can be done by breast self-examination, though this approach was discredited by a 2005 study in over 300,000 Chinese women. Screening for breast cancer with mammograms has been shown to reduce the average stage of diagnosis of breast cancer in a population. Stage of diagnosis in a country has been shown to decrease within ten years of introduction of mammographic screening programs. Colorectal cancer can be detected through fecal occult blood testing and colonoscopy, which reduces both colon cancer incidence and mortality, presumably through the detection and removal of pre-malignant polyps. Similarly, cervical cytology testing (using the Pap smear) leads to the identification and excision of precancerous lesions. Over time, such testing has been followed by a dramatic reduction of cervical cancer incidence and mortality. Testicular self-examination is recommended for men beginning at the age of 15 years to detect testicular cancer. Prostate cancer can be screened using a digital rectal exam along with prostate specific antigen (PSA) blood testing, though some authorities (such as the US Preventive Services Task Force) recommend against routinely screening all men.

Screening for cancer is controversial in cases when it is not yet known if the test actually saves lives. The controversy arises when it is not clear if the benefits of screening outweigh the risks of follow-up diagnostic tests and cancer treatments. For example: when screening for prostate cancer, the PSA test may detect small cancers that would never become life threatening, but once detected will lead to treatment. This situation, called overdiagnosis, puts men at risk for complications from unnecessary treatment such as surgery or radiation.

Follow up procedures used to diagnose prostate cancer (prostate biopsy) may cause side effects, including bleeding and infection. Prostate cancer treatment may cause incontinence (inability to control urine flow) and erectile dysfunction (erections inadequate for intercourse). Similarly, for breast cancer, there have recently been criticisms that breast screening programs in some countries cause more problems than they solve. This is because screening of women in the general population will result in a large number of women with false positive results which require extensive follow-up investigations to exclude cancer, leading to having a high number-to-treat (or number-to-screen) to prevent or catch a single case of breast cancer early.

Cervical cancer screening via the Pap smear has the best cost-benefit profile of all the forms of cancer screening from a public health perspective as, being largely caused by a virus, it has clear risk factors (sexual contact), and the natural progression of cervical cancer is that it normally spreads slowly over a number of years therefore giving more time for the screening program to catch it early. Moreover, the test itself is easy to perform and relatively cheap.

For these reasons, it is important that the benefits and risks of diagnostic procedures and treatment be taken into account when considering whether to undertake cancer screening.

Use of medical imaging to search for cancer in people without clear symptoms is similarly marred with problems. There is a significant risk of detection of what has been recently called an incidentaloma - a benign lesion that may be interpreted as a malignancy and be subjected to potentially dangerous investigations. Recent studies of CT scan-based screening for lung cancer in smokers have had equivocal results, and systematic screening is not recommended as of July 2007. Randomized clinical trials of plain-film chest X-rays to screen for lung cancer in smokers have shown no benefit for this approach.

Canine cancer detection has shown promise, but is still in the early stages of research.

Diagnosis

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http://en.wikipedia.org/skins-1.5/common/images/magnify-clip.png Chest x-ray showing lung cancer in the left lung

Most cancers are initially recognized either because signs or symptoms appear or through screening. Neither of these lead to a definitive diagnosis, which usually requires the opinion of a pathologist, a type of physician (medical doctor) who specializes in the diagnosis of cancer and other diseases. People with suspected cancer are investigated with medical tests. These commonly include blood tests, X-rays, CT scans and endoscopy.

Management

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Many management options for cancer exist including: chemotherapy, radiation therapy, surgery, immunotherapy, monoclonal antibody therapy and other methods. Which are used depends upon the location and grade of the tumour and the stage of the disease, as well as the general state of a person’s health. Experimental cancer treatments are also under development.

Complete removal of the cancer without damage to the rest of the body is the goal of treatment. Sometimes this can be accomplished by surgery, but the propensity of cancers to invade adjacent tissue or to spread to distant sites by microscopic metastasis often limits its effectiveness. The effectiveness of chemotherapy is often limited by toxicity to other tissues in the body. Radiation can also cause damage to normal tissue.

Because "cancer" refers to a class of diseases, it is unlikely that there will ever be a single "cure for cancer" any more than there will be a single treatment for all infectious diseases. Angiogenesis inhibitors were once thought to have potential as a "silver bullet" treatment applicable to many types of cancer, but this has not been the case in practice.

Emotional impact

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Many local organizations offer a variety of practical and support services to people with cancer. Support can take the form of support groups, counseling, advice, financial assistance, transportation to and from treatment, films or information about cancer. Neighborhood organizations, local health care providers, or area hospitals may have resources or services available.

Counseling can provide emotional support to cancer patients and help them better understand their illness. Different types of counseling include individual, group, family, peer counselling, bereavement, patient-to-patient, and sexuality.

Many governmental and charitable organizations have been established to help patients cope with cancer. These organizations are often involved in cancer prevention, cancer treatment, and cancer research.

Research

Cancer research is the intense scientific effort to understand disease processes and discover possible therapies. The improved understanding of molecular biology and cellular biology due to cancer research has led to a number of new, effective treatments for cancer since President Nixon declared "War on Cancer" in 1971. Since 1971 the United States has invested over $200 billion on cancer research; that total includes money invested by public and private sectors and foundations. Despite this substantial investment, the country has seen a five percent decrease in the cancer death rate (adjusting for size and age of the population) between 1950 and 2005. Leading cancer research organizations and projects include the American Association for Cancer Research, the American Cancer Society (ACS), the American Society of Clinical Oncology, the European Organisation for Research and Treatment of Cancer, the National Cancer Institute, the National Comprehensive Cancer Network, and The Cancer Genome Atlas project at the NCI.