CANCER

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.

Cancer may affect people at all ages, even fetuses, but the risk for most varieties increases with age. Cancer causes about 13% of all deaths. According to the American Cancer Society, 7.6 million people died from cancer in the world during 2007. Cancers can affect all animals.

Nearly all cancers are caused by abnormalities in the genetic material of the transformed cells

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.

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. The prognosis of cancer patients is most influenced by the type of cancer, as well as the stage, or extent of the disease.

Glossary

• Malignant neoplasm or malignant tumor: synonymous with cancer.
• Invasive tumor is another synonym of cancer. The name refers to invasion of surrounding tissues.
• Pre-malignancy, pre-cancer or non-invasive tumor: A neoplasm that is not invasive but has the potential to progress to cancer (become invasive) if left untreated.
  

The following terms can be used to describe a cancer:.

• Metastasis: new tumors that appear far from the original tumor.
• Chemotherapy: treatment with drugs.
• Radiation therapy: treatment with radiations.
• Adjuvant therapy: treatment, either chemotherapy or radiation therapy, given after surgery to kill the remaining cancer cells.

Classification

A large invasive ductal carcinoma in a mastectomy specimen.

Cancers are classified by the type of cell that resembles the tumor and, therefore, the tissue presumed to be the origin of the tumor.

• Carcinoma: Malignant tumors derived from epithelial cells. This group represents the most common cancers, including the common forms of breast, prostate, lung and colon cancer.
• Sarcoma: Malignant tumors derived from connective tissue, or mesenchymal cells.
• Lymphoma and leukemia: Malignancies derived from hematopoietic (blood-forming) cells

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.

Benign tumors (which are not cancers) are named using -oma as a suffix with the organ name as the root. Unfortunately, some cancers also use the -oma suffix, examples being melanoma and seminoma.

Signs and symptoms

Symptoms of cancer metastasis depend location of the tumor.

Roughly, cancer symptoms can be divided into three groups:

Although advanced cancer may cause pain, it is often not the first symptom.

Cancer may be a common or uncommon cause of each item.

Causes

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).

The errors which cause cancer are often self-amplifying, eventually compounding (like money) at an exponential rate.

• A mutation in signaling (endocrine) machinery of the cell can send error-causing signals to nearby cells

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 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.

Mutation: chemical carcinogens

Cancer pathogenesis is traceable back to DNA mutations that impact cell growth and metastasis. Substances that cause DNA mutations are known as mutagens, and mutagens that cause cancers are known as carcinogens. Particular substances have been linked to specific types of cancer. Tobacco smoking is associated with many forms of cancer, and causes 90% of lung cancer.

The incidence of lung cancer is highly correlated with smoking.

Mutation: ionizing radiation

Sources of ionizing radiation, such as radon gas, can cause cancer.

Viral or bacterial infection

Some cancers can be caused by infection with pathogens. Many cancers originate from a viral infection; this is especially true in animals such as birds, but also in humans, as viruses are responsible for 15% of human cancers worldwide. This induces uncontrolled cell division.

Liver cirrhosis, whether from chronic viral hepatitis infection or alcoholism, is associated with the development of liver cancer, and the combination of cirrhosis and viral hepatitis presents the

highest risk of liver cancer development. Worldwide, liver cancer is one of the most common, and most deadly, cancers due to a huge burden of viral hepatitis transmission and disease.

Advances in cancer research have made a vaccine designed to prevent cancer available.

Hormonal imbalances

A well-established example is the role of hyperestrogenic states in promoting endometrial cancer.

Immune system dysfunction

HIV is associated with a number of malignancies, including Kaposi's sarcoma, non-Hodgkin's lymphoma, and HPV-associated malignancies such as anal cancer and cervical cancer.

Heredity

Most forms of cancer are "sporadic", and have no basis in heredity. There are, however, a number of recognised syndromes of cancer with a hereditary component, often a defective tumor suppressor allele. Famous examples are:

• certain inherited mutat ions in the genes BRCA1 and BRCA2 are associated with an elevated risk of breast cancer and ovarian cancer
• Li-Fraumeni syndrome (various tumors such as osteosarcoma, breast cancer, soft tissue sarcoma, brain tumors) due to mutations of p53
• Hereditary nonpolyposis colorectal cancer (HNPCC, also known as Lynch syndrome) can include familial cases of colon cancer, uterine cancer, gastric cancer, and ovarian cancer, without a preponderance of colon polyps..

Other causes

In non-humans, a few types of cancer have been found to be caused by transmission of the tumor cells themselves.

Mechanism

Cancers are caused by a series of mutations.

Cancer is fundamentally a disease of regulation of tissue growth. In order for a normal cell to transform into a cancer cell, genes which regulate cell growth and differentiation must be altered. Tumor suppressor genes are genes which inhibit cell division, survival, or other properties of cancer cells. Tumor suppressor genes are often disabled by cancer-

promoting genetic changes. Typically, changes in many genes are required to transform a normal cell into a cancer cell.

There is a diverse classification scheme for the various genomic changes which may contribute to the generation of cancer cells.

Epigenetics

Loss of that methylation can induce the aberrant expression of oncogenes, leading to cancer pathogenesis. Classes of medications, known as HDAC inhibitors and DNA methyltransferase inhibitors, can re-regulate the epigenetic signaling in the cancer cell.

Oncogenes

Oncogenes promote cell growth through a variety of ways. One of the first oncogenes to be defined in cancer research is the ras oncogene.

Tumor suppressor genes

Tumor suppressor genes code for anti-proliferation signals and proteins that suppress mitosis and cell growth.

Despite nearly half of all cancers possibly involving alterations in p53, its tumor suppressor function is poorly understood.

Mutations of tumor suppressor genes that occur in germline cells are passed along to offspring, and increase the likelihood for cancer diagnoses in subsequent generations. The tumor types are typical for each type of tumor suppressor gene mutation, with some mutations causing particular cancers, and other mutations causing others. Other inherited tumor suppressor gene syndromes include Rb mutations, linked to retinoblastoma, and APC gene mutations, linked to adenopolyposis colon cancer. Adenopolyposis colon cancer is associated with thousands of polyps in colon while young, leading to colon cancer at a relatively early age. Finally, inherited mutations in BRCA1 and BRCA2 lead to early onset of breast cancer.

Inactivation of one allele of some tumor suppressor genes is sufficient to cause tumors.

Cancer cell biology

Tissue can be organized in a continuous spectrum from normal to cancer.

Often, the multiple genetic changes which result in cancer may take many years to accumulate. During this time, the biological behavior of the pre-malignant cells slowly change from the properties of normal cells to cancer-like properties. Dysplasia is an abnormal type of excessive cell proliferation characterized by loss of normal tissue arrangement and cell structure in pre-malignant cells.

Clonal evolution

However once cancer begins, cancer cells undergo a process of natural selection: the few cells with new genetic changes

that enhance their survival or reproduction continue to multiply, and soon come to dominate the growing tumor, as cells with less favorable genetic change are out-competed. This evolution is why cancer recurrences will have cells which have acquired cancer-drug resistance (or in some cases, resistance to radiation from radiotherapy).

Biological properties of cancer cells

When normal cells are damaged beyond repair, they are eliminated by apoptosis (A). Cancer cells avoid apoptosis and continue to multiply in an unregulated manner (B).

Not all the cancer cells are dividing. Rather, a subset of the cells in a tumor, called cancer stem cells, replicate themselves and generate differentiated cells.

Prevention

Cancer prevention is defined as active measures to decrease the incidence of cancer.

Modifiable ("lifestyle") risk factors

A squamous cell carcinoma (the whitish tumor) near the bronchi in a lung specimen.

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, esophageal, 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).

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

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. 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.

An invasive colorectal carcinoma (top center) in a colectomy specimen.

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.

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".

Vitamins

This has largely not been proven to be the case with cancer, and vitamin supplementation is largely not proving effective in preventing cancer.

Epidemiological studies have shown that low vitamin D status is correlated to increased cancer risk.This effect was particularly strong in lung cancer.

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

Screening

Cancer screening is an attempt to detect unsuspected cancers in an asymptomatic population. Screening for cancer can lead to earlier diagnosis in specific cases. Screening for breast cancer with mammograms has been shown to reduce the average stage of diagnosis of breast cancer in a population. 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. 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. Prostate cancer treatment may cause incontinence (inability to control urine flow) and erectile dysfunction (erections inadequate for intercourse).

Diagnosis

Most cancers are initially recognized either because signs or symptoms appear or through screening.

Investigation

Chest x-ray showing lung cancer in the left lung.

People with suspected cancer are investigated with medical tests.

Treatment

Cancer can be treated by surgery, chemotherapy, radiation therapy, immunotherapy, monoclonal antibody therapy or other methods. A number of 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.

Surgery

This has given rise to the popularity of local-only treatments such as surgery for small cancers.

Examples of surgical procedures for cancer include mastectomy for breast cancer and prostatectomy for prostate cancer. A single cancer cell is invisible to the naked eye but can regrow into a new tumor, a process called recurrence.

Radiation therapy

Radiation therapy (also called radiotherapy, X-ray therapy, or irradiation) is the use of ionizing radiation to kill cancer cells and shrink tumors. Although radiation damages both cancer cells and normal cells, most normal cells can recover from the effects of radiation and function properly. The goal of radiation therapy is to damage as many cancer cells as possible, while limiting harm to nearby healthy tissue.

Chemotherapy

Chemotherapy is the treatment of cancer with drugs ("anticancer drugs") that can destroy cancer cells. Most forms of chemotherapy target all rapidly dividing cells and are not specific to cancer cells, although some degree of specificity may come from the inability of many cancer cells to repair DNA damage, while normal cells generally can.

Targeted therapies

This constitutes the use of agents specific for the deregulated proteins of cancer cells. Small molecule targeted therapy drugs are generally inhibitors of enzymatic domains on mutated, overexpressed, or otherwise critical proteins within the cancer cell.

Photodynamic therapy (PDT) is a ternary treatment for cancer involving a photosensitizer, tissue oxygen, and light (often using lasers). PDT can be used as treatment for basal cell carcinoma (BCC) or lung cancer; PDT can also be useful in removing traces of malignant tissue after surgical removal of large tumors.

Immunotherapy

A renal cell carcinoma (lower left) in a kidney specimen.

Cancer immunotherapy refers to a diverse set of therapeutic strategies designed to induce the patient's own immune system to fight the tumor.

Hormonal therapy

The growth of some cancers can be inhibited by providing or blocking certain hormones. Common examples of hormone-sensitive tumors include certain types of breast and prostate cancers.

Symptom control

Although the control of the symptoms of cancer is not typically thought of as a treatment directed at the cancer, it is an important determinant of the quality of life of cancer patients, and plays an important role in the decision whether the patient is able to undergo other treatments.

Chronic pain due to cancer is almost always associated with continuing tissue damage due to the disease process or the treatment (i.e. surgery, radiation, chemotherapy).

Treatment trials

Clinical trials, also called research studies, test new treatments in people with cancer. The goal of this research is to find better ways to treat cancer and help cancer patients. Studies are done with cancer patients to find out whether promising treatments are safe and effective.

Complementary and alternative

CAM use is common among people with cancer; a 2000 study found that 69% of cancer patients had used at least one CAM therapy as part of their cancer treatment. Most complementary and alternative medicines for cancer have not been rigorously studied or tested.

In pregnancy

Some forms of skin cancer may even metastasize to the child's body.

Prognosis

Cancer has a reputation for being a deadly disease.

Progressive and disseminated malignant disease has a substantial impact on a cancer patient's quality of life, and many cancer treatments (such as chemotherapy) may have severe side-effects. In the advanced stages of cancer, many patients need extensive care, affecting family members and friends.

Emotional impact

Counseling can provide emotional support to cancer patients and help them better understand their illness.

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.

Epidemiology

In the U.S., lung cancer causes about 30% of cancer deaths but only about 15% of new cancer cases; the most commonly occurring cancer in men is prostate cancer (about 25% of new cases) and in women is breast cancer (also about 25%). In developed countries overweight and obesity is also a leading cause of cancer, and in low-and-middle-income countries sexual transmission of human papillomavirus is a leading risk factor for cervical cancer.

History

Typical macroscopic appearance of cancer.

Hippocrates described several kinds of cancers. The first cause of cancer was identified by British surgeon Percivall Pott, who discovered in 1775 that cancer of the scrotum was a common disease among chimney sweeps. The use of surgery to treat cancer had poor results due to problems with hygiene. With radiation also came the first signs of multi-disciplinary approaches to cancer treatment.

Research directions

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. 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.