It is clear that genes play a role in causing prostate cancer, just as they are thought to play a role in causing most other forms of cancer. Family studies, especially of twins, show that if your brother or father (first-degree relatives, who share half your genes) or uncle or grandfather (second-degree relatives, who share a quarter of your genes) had prostate cancer, your chances of getting it are approximately twice as high as if they did not. An affected brother increases your risk a little more than an affected father, and an affected brother or father increases your risk a little more than an affected uncle or grandfather.15

If two of your first-degree relatives had prostate cancer, your chances of getting it are five times greater than if none of them had it. If three first-degree relatives had prostate cancer, your chances of getting it are ten times greater. In one family, five out of six brothers developed prostate cancer.16 Such family clusters are rare, but when they occur, the cancer tends to appear at a young age.

If your family members had cancer in organs other than the prostate, does that increase your risk? Some studies have suggested that having breast or brain cancer in the family increases your risk of prostate cancer, but not all studies agree. The prostate cancer risk appears to be greater if your female relative had the rare, genetic-type breast cancer caused by BRCA genes, which are known to predispose to breast cancer.

Studying cancer in twins is another way to look for genetic clues. Since identical twins share the same genes but fraternal twins share only half their genes, like all other brothers, one would expect prostate cancer to appear in both identical twins more often than in both fraternal twins if genes play a major causative role. And that is what we find. Studies performed in Sweden, Denmark, and Finland, where national twin registries enable such research, show that if the first twin has prostate cancer, the second twin in a fraternal pair will get it 3 percent of the time, but the second twin in an identical pair will get it 18 percent of the time.17

These studies show that genes play some role in causing prostate cancer. Researchers have tried hard to identify genes that might be involved and have reported suspicious ''candidate'' genes on almost every chromosome. Examples include the RNASEL gene on chromosome 1, the MSR1 gene on chromosome 8, and the ELAC2 gene on chromosome 17. Evidence linking these specific genes to prostate cancer, however, is still rather weak. Another type of genetic abnormality, the fusion of two genes, was reported in late 2005 to occur in 80 percent of prostate cancers but not in normal prostate tissue; the question remains whether this is a cause of the cancer or an effect.

The latest trend in genetics research is to look at polymorphisms of candidate genes. If a gene were a car, a polymorphism would be a car with a dented fender. It is a particular variant of a gene and helps determine how active the gene is. Polymorphisms may be inherited and have therefore been invoked to try to explain why some ethnic groups are more predisposed than others to prostate cancer. Genes being closely studied for polymorphisms include those regulating testosterone and other androgens that, as will be explained shortly, may play a significant role in prostate cancer. An example of a recently reported gene polymorphism thought to be associated with prostate cancer is the KLF6 gene, which functions to suppress cell growth.

As recently summarized by one researcher, the evidence ''points toward a much more complex genetic basis of prostate cancer than initially anticipated.''18 Genes certainly play some role, but the role may be more modest than many researchers originally expected. Some investigators have concluded that only 5 to 10 percent of prostate cancers have a hereditary basis.19 The fact is that among identical twin pairs, who share the same genes, only one twin gets prostate cancer in the vast majority of cases. And men who migrate from low-risk countries to high-risk countries rapidly increase their risk without changing their genes. Nongenetic factors are obviously very important.

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