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Prostate cancer - genetic and other markers

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Illustrations

Male reproductive anatomy
Male reproductive anatomy
Prostate cancer
Prostate cancer
PSA blood test
PSA blood test

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AMACR

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The second leading cause of cancer death in American men is prostate cancer. (Lung cancer is first.) In 2002, doctors told an estimated 189,000 men that they have the potentially fatal disease. In an effort to lower these numbers in the future, researchers are investigating many possible markers for prostate cancer. These markers may one day help identify men at higher risk.

For example, a gene called AMACR (x-methylacyl-CoA racemase) appears to trigger production of a specific protein found only in cancer cells. This gene has been identified as a potential prostate cancer marker by several groups of researchers. The findings suggest that AMACR could eventually help pinpoint early prostate cancer and enhance diagnostic accuracy. In theory, a blood test for the gene could reduce the need for needle biopsies of the prostate.

"Since AMACR enzymatic activity is not found in most normal tissues, it could be used to…develop molecular probes for noninvasive detection of prostate cancer," says June Luo, Ph.D., lead author of a Johns Hopkins study.

The protein produced by AMACR helps the body metabolize certain fatty acids, such as those found in dairy products and beef. Researchers caution that the link, if any, between an overexpression of AMACR and a man's diet warrants further study.

Another area of active research is called proteomics. Proteomics identifies small amounts of proteins, peptides, and other small molecules in a patient's blood serum using a technique called mass spectrometry. Recent evidence indicates that patterns of these molecules are highly specific and sensitive for a variety of cancers, including prostate, ovarian, and many others. One possible advantage of this approach would be to identify patients with cancer without needing to do a biopsy, or as a way to better determine who should undergo a biopsy.

Interest in proteomics has risen partly due to the completion of the human genome project. Humans may contain as few as 30,000 genes, far fewer than had been predicted. With this finding has come the realization that cancer largely involves protein abnormalities, including abnormal structure, location in the cell, synthesis, turnover, interactions with other proteins and molecules, and modifications such as the addition of phosphate groups (phosphorylation) or sugar residues (glycosylation).

While proteomics is still in the investigational stage and not routinely used for diagnostic or treatment decisions at this time, it is expected that advances in this field over the next several years might have relevant and important clinical applications.

In the meantime, the medical community is deeply divided over the issue of screening for prostate cancer. At this time, there is no evidence that detecting prostate cancer early saves lives, and it is possible that the harm caused by subsequent procedures such as surgery, radiation, hormonal therapy or chemotherapy may outweigh any possible benefit.

Update Date: 5/24/2004

Updated by: Stephen Grund, M.D. Ph.D., Chief of Hematology/Oncology and Director of the George Bray Cancer Center at New Britain General Hospital, New Britain, CT. Review provided by VeriMed Healthcare Network.

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