CANCER, DRUGS, AND ALCOHOL

The relationship between cancer and drugs, including alcohol, has several aspects. One is the question of carcinogenesis; that is, whether alcohol and other abused substances cause cancer. Another is the relationship between prescription medications and cancer. A third is the complications of cancer treatment in patients with a history of substance abuse.

CARCINOGENESIS

The likelihood of a substance to cause cancer is called carcinogenicity; this is determined in several ways. The first is to see if cells grown in vitro (in a test tube) with the potential carcinogen develop cell-structure abnormalities in the new-grown cells. The second is to see if the substance will result in cancers in animals. The third is to look at the clinical course of a disease in a human patient. Finally, the outcomes in a group of people exposed to the substance will be compared to outcomes in those not exposed—either by following the natural course of history in a population through time in cohort studies or in case-control.

In spite of these methods, however, identifying carcinogens is complex and difficult. One reason is the long time delay between use of a carcinogenic chemical and the appearance of cancer symptoms; intervals of 20-30 years are not unusual. As a result, carcinogenic effects are rarely detected in early studies of new medications. Secondly, carcinogenesis appears to be a multistep process involving environmental, nutritional, and genetic factors as well as use of a carcinogenic drug.

Carcinogens are classified as genotoxic or epigenetic. Genotoxic carcinogens act directly on the DNA in human cells, in effect producing abnormal cells. Almost all identified drug carcinogens, however, fall into the second category, the epigenetic carcinogens. These substances encourage the proliferation of latent tumor cells in a tissue or organ.

DRUGS OF ABUSE AND CANCER

Alcohol.

Animal data do not show that administering Alcohol alone causes cancer although there is sufficient evidence for the carcinogenicity of acetaldehyde (the major metabolite of alcohol). When alcohol was administered to animals who were also exposed to known carcinogens, the animals who were given the alcohol had a higher rate of tumors of pituitary and adrenal glands, pancreatic islet cells, esophagus, and lungs. They also had higher levels of liver-cell (hepatocellular) carcinomas, liver angiosarcomas, and neoplastic nodules of the liver, as well as benign tumors of the nasal cavity and trachea.

Cancers of the Digestive Tract. Epidemiological studies in humans have shown a causal relationship between alcohol consumption and cancer of the digestive tract, primarily cancer of the oral cavity, the pharynx (nasopharynx excluded), and the larynx—all two to five times more likely in alcoholics; the esophagus—two to four times more likely; and the liver—liver cancer was increased 50 percent, with primary liver cancer increasing twofold to threefold. These findings persisted, even after adjusting for the effects of smoking, with the relative risk for cancer increasing with the amount of alcohol consumed.

There may be a possible causal link between alcohol, especially beer, and cancer of the large bowel. The risk for colon cancer was increased between 15 percent and threefold depending on the study; that for rectal cancer was increased up to twofold. Unfortunately, these studies did not control for differences in diet.

The mechanism of carcinogenic action appears to be that alcohol acts as a local irritant to the upper gastrointestinal tract, whereas chronic excessive drinking affects the liver, because of the accumulation of the alcohol metabolite acetaldehyde.

Breast Cancer. A strong association exists between alcohol and breast cancer, and there appears to be a dose-response relationship with an apparent relative risk of 1.5 to 2. This relationship holds even after controlling for a number of other factors known to affect breast cancer. As the full etiology (cause) of breast cancer is not yet known, an as-yet-unrecognized factor may account for some of these findings. Overall, it has been estimated that as many as 10 percent of all cancer deaths are due to alcohol.

Tobacco and Illicit Drugs.

The role of Tobacco as a carcinogen is well established and is discussed elsewhere. The role of other drugs as a cause of cancer is still unclear. Some drugs may have a role in cancer development because of mode of administration or degree of carcinogenicity. In vitro studies have shown mutagenic properties in a number of drugs—Lysergic Acid Diethylamide (LSD), Opium and its derivatives such as Mor-Phine, synthetic narcotics such as Methadone, and some compounds found in Marijuana. There have been clinical reports of cancers in the respiratory tract, primarily the lungs, in heavy marijuana users, of the nasal passages in cocaine users, and in a number of organs in LSD users. Higher rates of esophageal cancer have been reported in opium smokers.

PRESCRIPTION DRUGS AND CANCER

Very few drugs that are suspected of causing cancer in humans are used in contemporary medical practice. Those that are, however, fall into two significant categories: alkylating agents that are used to treat cancer; and birth control pills and other hormone preparations.

Alkylating agents.

These antineoplastic drugs include busulfan (Myleran), used to treat leukemia that has not responded to other drugs; cyclophosphamide (Cytoxan), an immunosuppressant used to treat ovarian cancer and malignant lymphoma; melphalan (Alkeran); ifosfamide (Ifex), used to treat testicular cancer and Ewing's sarcoma; cisplatin (Platinol), a drug derived from platinum; and chlorambucil (Leukeran), used in the treatment of leukemia and Hodgkin's disease. All of these drugs have serious side effects ranging from liver toxicity to fibrosis of the lungs, as well as carcinogenic potential. Cyclophosphamide in particular increases a patient's risk of secondary cancers for several years after it has been discontinued.

Synthetic Hormones and Steroid Preparations.

The natural and synthetic estrogens used for contraception and for postmenopausal hormone replacement have been associated with an increased risk of uterine cancer. As of the late 1990s, these estrogens are usually combined with progestins, which appear to lower this risk. Diethylstilbestrol (DES), which is used to treat menopausal symptoms and advanced cancers of the breast, may cause vaginal or cervical cancer in women whose mothers took DES during pregnancy. Oxymetholone (Anadrol), a steroid related to testosterone, is reported to increase the risk of liver cancer.

SUBSTANCE ABUSE AND CANCER TREATMENT

On the one hand, Narcotic and psychoactive drugs have an important role in cancer treatment. Cancer patients have used Cannabis sativa (marijuana) to reduce the nausea associated with chemo-therapy. LSD has been used in treating psychological disturbances associated with cancer. Although it was once feared that cancer patients would become addicted to opioids given for pain control, a recent study showed that of 11,882 cancer patients with no prior substance abuse history, only four became addicts after treatment with opioids.

On the other hand, preexisting abuse of these same substances complicates cancer treatment. A history of substance abuse may shorten a cancer patient's life expectancy and undermine the effectiveness of palliative care. Ongoing substance abuse disrupts the patient's relationships with physicians and other caregivers. As of 2000, the National Cancer Institute has issued guidelines for the clinical management of cancer patients with substance abuse histories. These guidelines include evaluation and treatment of comorbid psychiatric disorders, evaluation of the patient's tolerance of drugs, and monitoring of hospital inpatients.

(See also: Complications: Immunologic )

BIBLIOGRAPHY

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Hardman, J.G., & Limbird, L. E. (Eds.) (1996). Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed. New York: McGraw-Hill.

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World Health Organization. (1988). Alcohol drinking—IARC monographs on the evaluation of carcinogenic risks to humans. Lyon, France: World Health Organization International Agency for Research on Cancer, vol. 44.

Manuella Adrian

Revised by Rebecca J. Frey