Origins of cancer

Cell division (proliferation) is a physiological process that occurs in almost all tissues and under many circumstances. Normally the balance between proliferation and cell death is tightly regulated to ensure the integrity of organs and tissues. Mutations in DNA that lead to cancer disrupt these orderly processes.

The uncontrolled and often rapid proliferation of cells can lead to either a benign tumor or a malignant tumor (cancer). Benign tumors do not spread to other parts of the body or invade other tissues, and they are rarely a threat to life unless they extrinsically compress vital structures. Malignant tumors can invade other organs, spread to distant locations (metastasize) and become life-threatening.

Molecular biology

Carcinogenesis (meaning literally, the creation of cancer) is the process of derangement of the rate of cell division due to damage to DNA.

Cancer is, ultimately, a disease of genes. Carcinogenesis usually requires multiple mutations in many genes, thus mutations in single gene is simply not enough. A cell divides without any regulatory manner when its normal program of proliferation is disrupted, and often times these disruptions are about promotion of mitogenic signals and suppression of anti-mitogenic signals. These two processes involve oncogenes, and tumor suppressor genes, respectively.

Proto-oncogenes, broadly defined, are genes whose gene products promote cellular growth. These products can be hormones, mitogens, cell surface receptors, members of intracellular signaling pathways, and transcription factors. Often mutations in these proto-oncogenes cause them to become overactive, thus signalling the cells to divide and undergo uncontrolled growth.

Tumor suppressor genes typically encode for anti-proliferation signals and proteins that suppresses mitosis. Generally tumor suppressors are transcription factors that are activated by cellular stress or DNA damage. Their main function is to arrest the progression of cell cycle before any DNA damage is repared. Otherwise, these genetic lesions, which may contribute to further genomic instability, may be passed on to daughter cells. Canonical tumor suppressors include p53, which is a transcription factor activated by many cellular stress including hypoxia and UV damage.

In general, mutations in both types of genes are required for cancer to occur. For example, a mutation limited to one oncogene would be suppressed by normal mitosis control (the Knudson or 1-2-hit hypothesis) and tumor suppressor genes. A mutation to only one tumor suppressor gene would not cause cancer either, due to the presence of many "backup" genes that duplicate its functions. It is only when enough proto-oncogenes have mutated into oncogenes, and enough tumor suppressor genes deactivated or damaged, that the signals for cell growth overwhelm the signals to regulate it, that cell growth quickly spirals out of control.

On a genetic side note, mutations in proto-oncogenes are dominant, or gain of function mutations, while mutations in tumor suppressors are recessive, or loss of function mutations. Each cell has two copies of a same gene (one inherited from each parent), and under most cases gain of function mutation in one copy of a particular proto-oncogene is enough to make that gene a true oncogene, while usually loss of function mutation need to happen in both copies of a tumor suppressor gene to render that gene completely non-functional. However, cases exist in which one loss of function copy of a tumor suppressor gene can render (or poison) the other copy non-functional, and this is called dominant negative effect. This is observed in many p53 mutations.

Tumor suppressors are indicated in many families with hereditary cancers. Members within these families have increased incidence and decreased latency of multiple tumors. The mode of inheritance of mutant tumor suppressors is that affected member inherits a defective copy from one parent, and a normal copy from another. Because mutations in tumor suppressers act in a recessive manner (note, however, there are exceptions), the loss of the normal copy creates the cancer phenotype. For instance, individuals who are heterozygous for p53 mutations are often victims of Li-Fraumeni Syndrome, and those who are heterozygous for Rb mutations develop retinoblastoma. Similarly, mutations in APC are linked to adenopolyposis colon cancer (thousands of polyps in colon while young), while mutations in BRCA lead to early onset of breast cancer (often bilateral).

Cancer is ultimately due to accumulation of genetic insults, which are fundamentally mutations in the DNA. Substances that cause these 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 lung cancer. Breathing asbestos fibers is associated with mesothelioma. Prolonged exposure to radiation, particularly ultraviolet radiation from the sun, leads to melanoma and other skin malignancies.

Even though most carcinogens are mutagens, some carcinogens are not. For instance estrogen is required for proliferation in a subset of breast tumor (estrogen-dependent breast cancer), even though estrogen does not induce DNA damage. These mitogens promote cancers through their stimulatory effect on the rate of cell mitosis. Faster rates of mitosis increasingly leave less time for DNA repair, therefore increasingly the likelihood of a genetic mistake being passed onto daughter cells, which in turn accumulates multiple mutations that may lead to carcinogenesis or progression of the disease.

Furthermore, many cancers are viral in origin; this is especially true in animals such as birds, but less so in humans. The mode of virally-induce tumors can be divided into two, acutely or slowly- transforming. In acutely transforming viruses, the viral particles carry a gene that encodes for a overactive oncogene called viral-oncogene (or v-onc), and the infected cell is transformed as soon as v-onc is expressed. In contrast, in slowly-transforming viruses, virus genome is inserted (viral genome insertion is obligatory part of retroviruses) near a proto-oncogene in the host genome and the viral promoter or other transcription regulatory elements in turn cause overexpression of that proto-oncogene, which in turn induces uncontrolled cellular proliferation. Because viral genome insertion is not specific to proto-oncogenes and the chance of insertion near that proto-onc is low, slowly-transforming viruses have very long tumor latency compared to acutely-transforming virus, which already carries the v-onc.

Most cases the etiology of cancer is unknown. However, with the help of molecular biological and gross karyotyping techniques, it is possible to characterize the mutations and chromosomal aberrations of tumor cells, and rapid progress is being made in prognosis based on the type and spectrum of mutations in some cases. For example, up to half of all tumors have a defective p53 gene, a tumor suppressor gene also known as "the guardian of the genome". This mutation is associated with poor prognosis, since those tumor cells are less likely to go into apoptosis (programmed cell death) when cells are challenged by chemotherapeutics and radiation.

Malignant tumors cells have distinct properties (examples):

• evading apoptosis (down-regulation of death ligands in tumor cells)
• unlimited growth potential (immortalitization) (loss of regulatory region of receptor)
• self-sufficiency of growth factors (see above)
• insensitivity to anti-growth factors (see above)
• increased cell division rate (loss of Rb, which induces mitosis arrest)
• altered ability to differentiate (expression of embryonic markers)
• no ability for contact inhibition (down-regulation of E-cadherin, a celllular adhesion molecule)
• ability to invade neighbouring tissues (expression of metalloproteinases, which break down extracellular matrix)
• ability to build metastases at distant sites
• ability to promote blood vessel growth (angiogenesis) (expression of VEGF)

Morphology

Cancer tissue has a distinctive appearance under the microscope. Among the distinguishing traits are a large number of dividing cells, variation in nuclear size and shape, variation in cell size and shape, loss of specialized cell features, loss of normal tissue organization, and a poorly defined tumor boundary. Immunohistochemistry and other molecular methods may characterise specific markers on tumor cells, which may aid in diagnosis and prognosis.

Biopsy and microscopical examination can also distinguish between malignancy and hyperplasia, which refers to tissue growth based on an excessive rate of cell division, leading to a larger than usual number of cells but with a normal orderly arrangement of cells within the tissue. This process is considered reversible. Hyperplasia can be a normal tissue response to an irritating stimulus, for example callus.

Dysplasia is an abnormal type of excessive cell proliferation characterized by loss of normal tissue arrangement and cell structure. Often such cells revert back to normal behavior, but occasionally, they gradually become malignant.

The most severe cases of dysplasia are referred to as "carcinoma in situ." In Latin, the term "in situ" means "in place", so carcinoma in situ refers to an uncontrolled growth of cells that remains in the original location and shows no propensity to invade other tissues. Nevertheless, carcinoma in situ may develop into an invasive malignancy and is usually removed surgically, if possible.

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. Examples are:

• certain inherited mutations in the genes BRCA1 and BRCA2 are associated with an elevated risk of breast cancer and ovarian cancer
• tumors of various endocrine organs in multiple endocrine neoplasia (MEN types 1, 2a, 2b)
• Li-Fraumeni syndrome (various tumors such as osteosarcoma, breast cancer, soft-tissue sarcoma, brain tumors) due to mutations of p53
• Turcot syndrome (brain tumors and colonic polyposis)
• Familial adenomatous polyposis an inherited mutation of the APC gene that leads to early onset of colon carcinoma.
• Retinoblastoma in young children is an inherited cancer

Environment and diet

The most consistent finding, over decades of research, is the strong association between tobacco use and cancers of many sites. Hundreds of epidemiological studies have confirmed this association. Further support comes from the fact that lung cancer death rates in the United States have mirrored smoking patterns, with increases in smoking followed by dramatic increases in lung cancer death rates and, more recently, decreases in smoking followed by decreases in lung cancer death rates in men. Up to half of all cancer cases can be attributed to smoking, diet, and environmental pollution.

Treatment of cancer

Cancer can be treated by surgery, chemotherapy, radiation therapy, immunotherapy or other methods. The choice of therapy depends upon the location and grade of the tumor and the stage of the disease, as well as the general state of the patient (performance status). 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. 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.

Surgery

If the tumor is localized, surgery is often the preferred treatment. Example procedures include mastectomy for breast cancer and prostatectomy for prostate cancer. The goal of the surgery can be either the removal of only the tumor, or the entire organ. Since a single cancer cell can grow into a sizable tumor, removing only the tumor leads to a greater chance of recurrence. A margin of healthy tissue is often resected to make sure all cancerous tissue is removed.

In addition to removal of the primary tumor, surgery is often necessary for staging, e.g. determining the extent of the disease and whether there has been metastasis to regional lymph nodes. Staging determines the prognosis and the need for adjuvant therapy.

Occasionally, surgery is necessary to control symptoms, such as spinal cord compression or bowel obstruction. This is referred to as palliative treatment.

Chemotherapy

Chemotherapy is the treatment of cancer with drugs ("anticancer drugs") that can destroy cancer cells. It interferes with cell division in various possible ways, e.g. with the duplication of DNA or the separation of newly formed chromosomes. Most forms of chemotherapy target all rapidly dividing cells and are not specific for cancer cells. Hence, chemotherapy has the potential to harm healthy tissue, especially those tissues that have a high replacement rate (e.g. intestinal lining). These cells usually repair themselves after chemotherapy.

Because some drugs work better together than alone, two or more drugs are often given at the same time. This is called "combination chemotherapy"; most chemotherapy regimens are given in a combination.

A novel technique involves taking samples of the patient's tissue before chemotherapy. These tissues samples are screened to ensure they do not contain cancerous cells. The samples are expanded using tissue engineering techniques, and are then re-implanted following high dose chemotherapy in order to recolonise the damaged and somewhat destroyed tissue. A variation upon this method uses allogenic samples (samples donated by a different donor) instead of the patient's own tissue⁴.

Immunotherapy

Immunotherapy is the use of immune mechanisms against tumors. These are used in various forms of cancer, such as breast cancer (trastuzumab/Herceptin®) but also in leukemia (gemtuzumab ozogamicin/Mylotarg®). The agents are monoclonal antibodies directed against proteins that are characteristic to the cells of the cancer in question, or cytokines that modulate the immune system's response.

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. Radiation therapy can be administered externally via external beam radiotherapy (EBRT) or internally via brachytherapy. The effects of radiation therapy are localised and confined to the region being treated. Radiation therapy injures or destroys cells in the area being treated (the "target tissue") by damaging their genetic material, making it impossible for these cells to continue to grow and divide. In addition, they cut off the blood supply to the cancer cells causing them to die in a process called necrosis. 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. Hence, it is given in many fractions, allowing healthy tissue to recover between fractions.

Radiation therapy may be used to treat almost every type of solid tumor, including cancers of the brain, breast, cervix, larynx, lung, pancreas, prostate, skin, stomach, uterus, or soft tissue sarcomas. Radiation is also used to treat leukemia and lymphoma. Radiation dose to each site depends on a number of factors, including the radiosensitivty of each cancer type and whether there are tissues and organs nearby that may be damaged by radiation. Thus, as with every form of treatment, radiation therapy is not without its side effects. These side effects include temporary (reversible) or permanent side effects (irreversible damage).

Hormonal suppression

The growth of nearly all tissues, including cancers, can be accelerated or inhibited by providing or blocking certain hormones. This allows an additional method of treatment for many cancers. Common examples of hormone-sensitive tumors include certain types of breast, prostate, and thyroid cancers. Removing or blocking estrogen, testosterone, or TSH, respectively, is often an important additional treatment.

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. Although all practicing doctors have the therapeutic skills to control pain, nausea, vomiting, diarrhea, hemorrhage and other common problems in cancer patients, the multidisciplinary specialty of palliative care has arisen specifically in response to the symptom control needs of this group of patients.

Analgesia (painkillers, frequently opioids such as morphine) and antiemetics (drugs to suppress nausea and vomiting) are very commonly used in patients with cancer-related symptoms.

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. Clinical trials test many types of treatment such as new drugs, new approaches to surgery or radiation therapy, new combinations of treatments, or new methods such as gene therapy.

A clinical trial is one of the final stages of a long and careful cancer research process. The search for new treatments begins in the laboratory, where scientists first develop and test new ideas. If an approach seems promising, the next step may be testing a treatment in animals to see how it affects cancer in a living being and whether it has harmful effects. Of course, treatments that work well in the lab or in animals do not always work well in people. Studies are done with cancer patients to find out whether promising treatments are safe and effective.

Patients who take part may be helped personally by the treatment(s) they receive. They get up-to-date care from cancer experts, and they receive either a new treatment being tested or the best available standard treatment for their cancer. Of course, there is no guarantee that a new treatment being tested or a standard treatment will produce good results. New treatments also may have unknown risks, but if a new treatment proves effective or more effective than standard treatment, study patients who receive it may be among the first to benefit.

Complementary and alternative medicine

Complementary and alternative medicine (CAM) treatments are the diverse group of medical and health care systems, practices, and products that are not presently considered to be effective by the standards of conventional medicine. Some non-conventional treatment methods are used to "complement" conventional treatment, to provide comfort or lift the spirits of the patient, while others are offered as alternatives to be used instead of conventional treatments in hope of curing the cancer.

Common complementary measures include prayer or psychological approaches such as "imaging" to aid in pain relief, or improve mood. Many people feel these approaches benefit them, but most have not been scientifically proven and therefore face skepticism. Other complementary approaches include traditional medicine like Traditional Chinese Medicine.

A wide range of alternative treatments have been offered for cancer over the last century. The appeal of alternative cures arises from the daunting risks, costs, or potential side effects of many conventional treatments, or in the limited prospect for cure. Proponents of these therapies are unable or unwilling to demonstrate effectiveness by conventional criteria. Alternative treatments have included special diets or dietary supplements (e.g., the "grape diet" or megavitamin therapy), electrical devices (e.g., "zappers"), specially formulated compounds (e.g., laetrile), unconventional use of conventional drugs (e.g., insulin), purges or enemas, or physical manipulations of the body. Some of these treatments meet all the criteria for fraud. Collectively they are referred to by skeptics as cancer quackery. An extensive, explanatory catalog of these treatments is available at Quackwatch [1]. Almost all physicians recommend against using these modalities as sole treatment for potentially fatal conditions such as cancer.

Epidemiology

In some Western countries, such as the USA¹ and the UK², cancer is overtaking cardiovascular disease as the leading cause of death. In many Third World countries cancer incidence (insofar as this can be measured) appears much lower, most likely because of the higher death rates due to infectious disease or injury. With the increased control over malaria and tuberculosis in some Third World countries, incidence of cancer is expected to rise; this is termed the iceberg phenomenon in epidemiological terminology.

Cancer epidemiology closely mirrors risk factor spread in various countries. Hepatocellular carcinoma (liver cancer) is rare in the West but is the main cancer in China and neighboring countries, most likely due to the endemic presence of hepatitis B and aflatoxin in that population. Similarly, with tobacco smoking becoming more common in various Third World countries, lung cancer incidence has increased in a parallel fashion.

Prevention

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

Much of the promise for cancer prevention comes from observational epidemiologic studies that show associations between modifiable life style factors or environmental exposures and specific cancers. Evidence is now emerging from randomized controlled trials designed to test whether interventions suggested by the epidemiologic studies, as well as leads based on laboratory research, actually result in reduced cancer incidence and mortality.

Examples of modifiable cancer risk include alcohol consumption (associated with increased risk of oral, esophageal, breast, and other cancers), physical inactivity (associated with increased risk of colon, breast, and possibly other cancers), and being overweight (associated with colon, breast, endometrial, and possibly other cancers). Based on epidemiologic evidence, it is now thought that avoiding excessive alcohol consumption, being physically active, and maintaining recommended body weight may all 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 sexual and reproductive practices, the use of exogenous hormones, exposure to ionizing radiation and ultraviolet radiation, certain occupational and chemical exposures, and infectious agents.

Diet and cancer

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). Studies have shown that immigrants develop the risk of their new country, suggesting a link between diet and cancer rather than a genetic basis.

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 on the basis of these studies until they have been validated in an observational (or occasionally a prospective interventional) trial in humans.

The case of beta-carotene provides an example of the necessity of randomized clinical trials. Epidemiologists studying both diet and serum levels observed that high levels of beta-carotene, a precursor to vitamin A, were associated with a protective effect, reducing the risk of cancer. This effect was particularly strong in lung cancer. This hypothesis led to a series of large randomized trials conducted in both Finland and the United States (CARET study) during the 1980s and 1990s. This study provided about 80,000 smokers or former smokers with daily supplements of beta-carotene or placebos. Contrary to expectation, these tests found no benefit of beta-carotene supplementation in reducing lung cancer incidence and mortality. In fact, the risk of lung cancer was slightly, but significantly, increased in smokers, leading to an early termination of the study³.

Other chemoprevention agents

Daily use of tamoxifen, a selective estrogen receptor modulator, for up to 5 years, has been demonstrated to reduce the risk of developing breast cancer in high-risk women by about 50%. Cis-retinoic acid also has been shown to reduce risk of second primary tumors among patients with primary head and neck cancer. Finasteride, a 5-alpha reductase inhibitor, has been shown to lower the risk of prostate cancer. Other examples of drugs that show promise for chemoprevention include COX-2 inhibitors (which inhibit a cyclooxygenase enzyme involved in the synthesis of proinflammatory prostaglandins).

Cancer vaccines

Considerable research effort is now devoted to the development of vaccines (to prevent infection by oncogenic infectious agents, as well as to mount an immune response against cancer-specific epitopes) and to potential venues for gene therapy for individuals with genetic mutations or polymorphisms that put them at high risk of cancer. No cancer vaccines are presently in use, and most of the research is still in its initial stages.

As of October 2005, researchers found that an experimental vaccine for HPV types 16 and 18 was 100% successful at preventing infection with these types of HPV and, thus, are able to prevent the majority of cervical cancer cases. [2]

Genetic testing

Genetic testing for high-risk individuals, with enhanced surveillance, chemoprevention, or risk-reducing surgery for those who test positive, is already available for certain cancer-related genetic mutations.

Coping with cancer

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, or information about cancer. Neighborhood organizations, local health care providers, or area hospitals are a good place to start looking.

While some people are reluctant to seek counseling, studies show that having someone to talk to reduces stress and helps people both mentally and physically. Counseling can also provide emotional support to cancer patients and help them better understand their illness. Different types of counseling include individual, group, family, self-help (sometimes called peer counseling), bereavement, patient-to-patient, and sexuality.

Many governmental and charitable organizations have been established to help patients cope with cancer. These organizations often are involved in cancer prevention, cancer treatment, and cancer research. Examples include: American Cancer Society, BC Cancer Agency, Macmillan Cancer Relief , the Terry Fox Foundation, Cancer Research UK, Canadian Cancer Society, International Agency for Research on Cancer and the National Cancer Institute (US).

Social impact

Once refered to as "the C-word," cancer has a reputation for being a deadly disease. While this certainly applies to certain particular types, the truths behind the historical connotations of cancer are increasingly being overturned by advances in medical care. Some types of cancer have a prognosis that is substantially better than nonmalignant diseases such as heart failure and stroke.

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. Palliative care solutions may include permanent or "respite" hospice nursing.

Cancer research

Cancer research is the intense scientific effort to understand disease processes and discover possible therapies. While understanding of cancer has increased exponentially since the last decades of the 20th century, radically new therapies are only discovered and introduced gradually.

Targeted therapy in the late 1990s was considered a major breakthrough. This constitutes the use of agents specific for the deregulated proteins of cancer cells. Small molecules (such as the tyrosine kinase inhibitors imatinib and gefitinib) and monoclonal antibodies have proven to be a major step in oncological treatment.

See also

• Oncology
• List of oncology-related terms
• Terminal illness

References

• Note 1: Jemal A, Murray T, Ward E, Samuels A, Tiwari RC, Ghafoor A, Feuer EJ, Thun MJ. Cancer statistics, 2005. CA Cancer J Clin 2005;55:10-30. Fulltext. PMID 15661684.
• Note 2: Cancer: Number one killer (9 November, 2000). BBC News online. Retrieved 2005-01-29.
• Note 3: Questions and Answers About Beta Carotene Chemoprevention Trials
• Note 4: Bilal A, Treating Cancer with Stem Cells, Medical Engineer, 25 July 2005 Fulltext

External links

Professional and research

• The World Health Organisation's cancer site A review of worldwide strategies for the prevention and treatment of cancer.
• Cancer Facts & Figures 2005 - 2005 United States Cancer Statistics
• Cancer Medicine, 6th Edition Textbook
• National Comprehensive Cancer Network - has free guidelines for professionals and many pages of quality information for patients with all types of cancers
• US National Cancer Institute Government organization for research and treatment
• EORTC European Organization for Research and Treatment of Cancer. A European non-profit organization that sets up and executes clinical trials.

Support and advocacy

• American Cancer Society Patient advocate group
• American Association for Cancer Research Largest scientific organization in the world
• Cancer from MedlinePlus - provides links to news, general sites, diagnosis, treatment and alternative therapies, clinical trials, research, related issues, organizations, other MedlinePlus Cancers Topics and Living with Cancer, and more. Also, links to pre-formulated searches of the MEDLINE/PubMed database for recent research articles.
• Cancer Research UK - Cancer Resources - In-depth, up-to-date information for people with a professional or general interest in cancer and health.
• Cancer Research UK - Cancer Help - Free information service about cancer and cancer care for people with cancer and their families.
• Wikicities has a wiki about cancer: Wikicities:c:cancer Cancer Help Infositeca:CГ ncer

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