hematology and oncology
Cellular and Molecular Basis of Cancer
Environmental Factors
 contribute to the pathogenesis of some human cancers (see table Cancer-Associated Viruses ). Pathogenesis may occur through the integration of viral genetic elements into host DNA. These new genes are expressed by the host; they may affect cell growth or division or disrupt normal host genes required for control of cell growth and division. Alternatively, viral infection may result in immune dysfunction, leading to decreased immune surveillance for early tumors. HIV infection increases the risk of a number of cancers (see Bacteriacan also cause cancer.Helicobacter pyloriinfection increases the risk of several kinds of cancer (gastric adenocarcinoma, gastric lymphoma, mucosa-associated lymphoid tissue [MALT] lymphoma). Parasitesof some types can lead to cancer.Schistosoma haematobiumcauses chronic inflammation and fibrosis of the bladder, which may lead to cancer.Opisthorchis sinensishas been linked to carcinoma of the pancreas and bile ducts. Ultraviolet radiationcan induce skin cancer (eg, basal and squamous cell carcinoma, melanoma) by damaging DNA. This DNA damage consists of formation of thymidine dimers, which may escape excision and re-synthesis of a normal DNA strand. Patients with inherent defects in DNA repair (eg, xeroderma pigmentosum) or immune suppression by drugs or an underlying disease are particularly prone to skin cancers due to ultraviolet exposure. is carcinogenic. For example, survivors of the atomic bomb explosions in Hiroshima and Nagasaki have a higher-than-expected incidence of leukemia and solid cancers. Similarly, exposure to therapeutic irradiation may lead to leukemia, breast cancer, sarcomas and other solid cancers years after exposure. Exposure to x-rays for diagnostic imaging studies is thought to increase risk of cancer (see Risks of Medical Radiation ). Occupational exposure (eg, to uranium by mine workers) is linked to development of lung cancer, particularly in smokers. Long-term exposure to occupational irradiation or to internally deposited thorium dioxide predisposes people to angiosarcomas and acute myeloid leukemia. Radon,a radioactive gas that is released from soil, increases the risk of lung cancer, especially in smokers. Normally, radon disperses rapidly into the atmosphere and causes no harm. However, when a building is placed on soil with high radon content, radon can accumulate, sometimes producing sufficiently high levels in the air to cause harm. Combinedestrogenand progestin oral contraceptives may slightly increase the risk of breast cancer, but this risk decreases over time.Estrogentherapy alone, withoutprogesterone, increases the risk of uterine cancer. These increased risks are modest. Diethylstilbestrol (DES) increases the risk of breast cancer in women who took the drug, and increases the risk of vaginal cancer in daughters of these women exposed before birth. Long-term use of anabolic steroids may increase the risk of liver cancer and accelerate prostate cancer. Treatment of cancer with chemotherapy drugs alone or with radiation therapy increases the risk of developing a second cancer, as do immunosuppressive drugs given for organ transplantation. The cancers most commonly increased due to immunosuppressive drugs are skin cancers (including melanoma), kidney cancer,and neuroblastoma.Hydroxyureaincreases the risk of skin cancer due to sun exposure, in addition to increasing the risk of acute leukemia in patients with myeloproliferative disorders (eg, polycythemia vera, thrombocythemia) treated long-term withhydroxyurea.Hydroxyureanot only causes 17p deletion, resulting in loss of aTP53 allele, it also impairs TP53 activation in patients with myeloproliferative disorders. Chemical carcinogens can induce gene mutations and result in uncontrolled growth and tumor formation (see table Common Chemical Carcinogens ). Other substances, called co-carcinogens, have little or no inherent carcinogenic potency but enhance the carcinogenic effect of another agent when exposed simultaneously. Certain substances consumed in the diet can increase the risk of cancer. For instance, a diet high in fat has been linked to an increased risk of colon, breast, and possibly prostate cancer. People who drink large amounts of alcohol are at higher risk of developing various cancers, including head and neck, liver, and esophageal cancer. A diet high in smoked and pickled foods or in meats cooked at a high temperature increases the risk of developing stomach cancer. People who are overweight or obese have a higher risk of cancer of many cancer types, particularly cancers of the breast, endometrium, colon, kidney, and esophagus. Chronic skin, lung, gastrointestinal, or thyroid inflammation may predispose to development of cancer. For example, patients with long-standing inflammatory bowel disease (ulcerative colitis) have an increased risk of colorectal carcinoma. Sunlight and tanning light exposure increases the risk of skin cancers and melanoma. 