The five factors discussed above are the leading candidates as contributors to the causation of prostate cancer. A multitude of other factors have been investigated, but none appear to be as promising. The most serious attention has been given to smoking, alcohol, va-sectomy, and exposure to dioxin or cadmium.
Smoking. Since smoking is a known risk factor for lung and bladder cancers, it has been extensively studied for other cancers as well. At least sixty-five research groups have examined smoking and prostate cancer, with the majority reporting no relationship.33 Men who smoke are more likely to consume a high-fat diet, which may explain research that has found a relationship. A few studies suggest that smoking hastens the spread of prostate cancer once it develops, but other studies have not confirmed this.
Alcohol. Heavy alcohol use is associated with cancers of the liver, larynx, and esophagus. At least thirty-five studies have examined alcohol use and prostate cancer. The conclusion of one review was that ''moderate alcohol consumption up to about three drinks per day does not appear to influence prostate cancer risk.''34 Equivocal support was found for the possibility that heavy alcohol use (eight or more drinks a day) may increase the risk. On the other hand, two studies of autopsy tissue taken from men who died from cirrhosis of the liver reported fewer instances of prostate cancer than expected. Cirrhosis increases the production of estrogens, which block testosterone, and thus slows the growth of prostate cancer. Severe alcoholism may therefore decrease the chances of developing prostate cancer.
Vasectomy. Surgical cutting of the vasa deferentia, the ducts that carry sperm from the testicles, is a common form of male contraception. Studies carried out in the 1980s and early 1990s suggested that men who had had a vasectomy, especially if it had been performed when they were relatively young, were at increased risk for prostate cancer. Subsequent studies have refuted this finding; a 1998 review of fourteen studies, for example, concluded that ''no causal association was found between vasectomy and prostate cancer.''35 It is now believed that earlier studies did not correct for selection bias; men who had had vasectomies were more likely to go to urologists for follow-up, and urologists in turn would have been more likely to look for prostate cancer in these men.
Dioxin. A component of some herbicides used by farmers and also of Agent Orange, a defoliant used during the Vietnam War, dioxin has been linked to a variety of cancers. Many, but not all, studies of occupational risk exposure have reported that prostate cancer occurs at a disproportionately high rate among farmers. A preliminary study of Vietnam veterans claimed that men with prostate cancer were approximately twice as likely as men without prostate cancer to report having been exposed to Agent Orange.36 A larger confirmatory study is needed.
Cadmium. The fact that asbestos causes mesothelioma, a form of cancer, has led to a suspicion that industrial carcinogens may cause other cancers. In addition, feeding various chemicals to rats can produce prostate cancer in them. In 1965 it was reported that an excess number of cases of prostate cancer had occurred in a factory where workers were exposed to cadmium. This finding was especially inter esting since cadmium inhibits zinc, which is in high concentration in the prostate. Extensive studies have subsequently been carried out on the incidence of prostate cancer among workers exposed to cadmium with the conclusion that there is ''no indication for an increased risk of prostate cancer'' among the workers.37
Despite having spent almost $200 billion since 1971 for a ''war on cancer,'' we know little more about the causes of prostate cancer now than when ''war'' was declared. At least seven clues should help direct our research.
1 Prostate cancer is found predominantly in older men.
2 Its incidence in the United States has apparently not changed in recent decades.
3 There are marked ethnic differences in incidence and death rates in the United States, with the rates for African Americans being high, for whites and Hispanics intermediate, and for Asian Americans and especially Native Americans low.
4 The incidence is very high in Scandinavian and Caribbean nations and very low in Asian nations; the United States is intermediate.
5 Men who migrate from low-incidence to high-incidence countries rapidly acquire the higher prevalence of their new country.
6 Other than humans, dogs are the only mammals that frequently get prostate cancer.
7 The incidence of prostate cancer among men with schizophrenia is low.
Genes play some role in causing prostate cancer, as indeed they do in causing most cancers and most chronic diseases. However, it does not appear that a man inherits genes that directly cause the cancer; rather, it seems likely that he inherits several genes that make it more likely that he will get cancer if he is exposed to a factor or factors whose identity is still unknown. Such genes are called predisposing genes.
Infectious agents should be carefully studied as possible causes of prostate cancer. To date, several suspects have been brought in for questioning but were released owing to lack of firm evidence. They continue to be under suspicion. Similarly, some aspects of sexual activity appear to play a role in causing prostate cancer, perhaps through having more sexual partners or increased exposure to sexually transmitted diseases.
Male sex hormones undoubtedly play a part in causing prostate cancer, but their specific role is uncertain. The hormonal changes could be a primary cause of the cancer or a secondary effect of diet, infectious agents, or other primary causes. Excess dietary fat has been extensively investigated as a cause of prostate cancer; recent studies suggest that it is a less likely trigger than previously believed. Excess calcium and zinc have also been studied as risk factors, with inconclusive results.
It is likely that some of these factors interact with others. For example, both dietary factors and infectious agents may affect male hormones, which in turn may increase sexual activity and result in sexually transmitted diseases that affect the prostate. In a genetically predisposed individual, such infections may result in cancer.
The biggest impediment to discovering the causes of prostate cancer is that the important events may occur early in life, even decades before the cancer becomes manifest.
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