Causes of Cancer

CAUSES OF CANCER

The incidence, geographic distribution, and behavior of specific types of cancer are related to multiple factors, including sex, age, race, genetic predisposition, and exposure to environmental carcinogens. Of these factors, environmental exposure is probably most important. Exposure to ionizing radiation has been well documented as a significant risk factor for a number of cancers, including acute leukemias, thyroid cancer, breast cancer, lung cancer, soft tissue sarcoma, and basal cell and squamous cell skin cancers. Chemical carcinogens (particularly those in tobacco smoke) as well as azo dyes, aflatoxins, asbestos, benzene, and radon have all been well documented as leading to a wide range of human cancers.

Several viruses have been implicated in the etiology of various human cancers. For example, hepatitis B and hepatitis C are asso-ciated with the development of hepatocellular cancer; HIV is associated with Hodgkin’s and non-Hodgkin’s lymphomas; human papillomavirus is associated with cervical cancer and head and neck cancer; and Ebstein-Barr virus is associated with nasopharyn-geal cancer. Expression of virus-induced neoplasia may also depend on additional host and environmental factors that modu-late the transformation process. Cellular genes are known that are homologous to the transforming genes of the retroviruses, a family of RNA viruses, and induce oncogenic transformation. 

These mammalian cellular genes, known as oncogenes, have been shown to code for specific growth factors and their corresponding recep-tors. These genes may be amplified (increased number of gene copies) or mutated, both of which can lead to constitutive overex-pression in malignant cells. The bcl-2 family of genes represents a series of pro-survival genes that promotes survival by directly inhibiting apoptosis, a key pathway of programmed cell death.

Another class of genes, known as tumor suppressor genes, may be deleted or mutated, which gives rise to the neoplastic phenotype. The p53 gene is the best-established tumor suppressor gene identi-fied to date, and the normal wild-type gene appears to play an important role in suppressing neoplastic transformation. Of note, p53 is mutated in up to 50% of all human solid tumors, includingliver, breast, colon, lung, cervix, bladder, prostate, and skin.

ACRONYMS

ABVD Doxorubicin (Adriamycin, hydroxydaunorubicin), bleo mycin, vinblastine, dacarbazine

CHOP Cyclophosphamide, doxorubicin (hydroxydaunorubi-

cin, Adriamycin), vincristine (Oncovin), prednisone

CMF  Cyclophosphamide, methotrexate, fluorouracil

COP   Cyclophosphamide, vincristine (Oncovin), prednisone

FAC 5-Fluorouracil, doxorubicin (Adriamycin, hydroxydauno-

rubicin), cyclophosphamide

FEC  5-Fluorouracil, epirubicin, cyclophosphamide

5-FU  5-Fluorouracil

FOLFIRI    5-Fluorouracil, leucovorin, irinotecan

FOLFOX   5-Fluorouracil, leucovorin, oxaliplatin

MP Melphalan, prednisone

6-MP 6-Mercaptopurine

MOPP Mechlorethamine, vincristine (Oncovin), procarbazine,

prednisone

MTX  Methotrexate

PCV  Procarbazine, lomustine, vincristine

PEB  Cisplatin (platinum), etoposide, bleomycin

6-TG 6-Thioguanine

VAD Vincristine, doxorubicin (Adriamycin), dexamethasone

XELOX      Capecitabine, oxaliplatin