In The News

Well-Done Meat Consumption May Increase Prostate Cancer Risk
Research into the dietary habits of about a thousand men from the Cleveland area has found that a high consumption of meats, especially of red meat prepared by grilling, is positively associated with an increased risk of developing aggressive prostate cancer. This particular study, which was led by Dr. John Witte of the University of California, San Francisco (UCSF), has a number of limitations, but it does add support to other investigations connecting meat consumption with cancer risk.

Toronto researchers speculate regarding a link between prostate cancer and oral contraceptive use
Very preliminary and speculative research, designed to spark further inquires, suggests that there may be a connection between oral contraceptive use and rising rates of prostate cancer. One theory is that the widespread use of birth-control pills in various populations may result in a higher level of estrogen in the environment, which might, in turn, increase prostate cancer risk.

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Closer to Better Identification of Aggressive Forms of Prostate Cancer

2/5/2011

Sorting aggressive and potentially lethal prostate cancer from the kind that is likely to remain dormant and confined to the prostate is a significant and ongoing research focus. A new study published online this month shows that researchers are closing in on this goal. It outlines plans for a gene-based prognostic test with the potential to determine aggressive and threatening forms of prostate cancer with more accuracy.

Researchers at the Dana-Farber Cancer Institute reported on February 2, 2011, in a study published by the journal Nature, that they have discovered a genetic "signature pattern" that helps predict, more accurately than current indicators, which prostate cancer patients will experience "recurrence and lethal metastasis" of their disease. This pattern is formed by the over-expression of key regulators cyclin D1 and SPP1 and the under-expression of PTEN and SMAD4.

Developing better prognostic tests of prostate cancer's aggressiveness is a difficult and important undertaking. It is difficult because, as lead researcher Dr. Ronald DePinho explains, "Human prostate cancers are extremely complex at the cellular and genomic levels." What this translates to, in non-medical terms, is a lack of uniformity, both in the cells of different tumours and in the cells of the same tumour. So one man's prostate cancer, which, in about 85 per cent of cases, has more than one tumour focus within the prostate gland, may have many different sorts of cancer cells with various and particular genetic abnormalities.

To account for this complexity, researchers combined data derived from analyzing the human prostate cancer tissue of sample participants in the Physicians' Health Study with data available from "refined mouse-models" derived from laboratory-based experiments to assess the metastatic or non-metastatic potential of prostate cancer. According to DePinho, this research strategy has met with a good result: "By integrating a variety of techniques --- computational biology, genetically engineered model systems, molecular and cellular biology, and human tissue microarrays --- we've identified a signature that has proven effective in distinguishing which men with prostate cancer are likely to progress and die from their disease and those who are not."

The company Metamark Genetics Inc. (of which DePinho is co-founder) has licensed the gene signature and technology developed in the course of this research and is working on a molecular prognostic test to "help guide physicians in determining the most appropriate treatment for each patient." (Note also that the research was funded in part by the Belfer Institute for Applied Cancer Science and the National Cancer Institute.)

Compared with the Gleason score, a standard way of assessing the level of abnormality and potential aggressiveness of a man's prostate cancer cells, the four-gene signature pattern is being touted as more accurate. And combining Gleason and the new method produces the best accuracy: approximately 90 per cent, according to researchers.

Discovering a better means of distinguishing potentially lethal prostate cancer from the less aggressive sort is essential. Why? Men diagnosed with localized prostate cancer are currently faced with a difficult decision. They can opt for an early treatment that has a very high probability of curing their disease but that might produce lasting complications, such as incontinence or erectile dysfunction, or they can choose active surveillance or a less common treatment, one without the established track records of surgery or radiation therapy. Estimates are, according to DePinho, that approximately 48 men are treated for prostate cancer for every life saved. "The vast majority of prostate cancers would not become life-threatening, even if left untreated," he says. The kicker with prostate cancer tumours, though, is that "we can't accurately forecast which are likely to spread and which aren't." At least not yet.

For more information on the choice between active surveillance or immediate treatment, see our article on this subject, written by John Hoffman.

Consult the following for more on the four-gene signature pattern:

Chin, Lynda, DePinho, Ronald A., and others, "SMAD4-dependent barrier constrains prostate cancer growth and metastatic progression," Nature, published online 2 February 2011.

"Metamark Genetics Announces Landmark Prostate Cancer Study Published in Nature," Metamark Genetics, Inc., February 2, 2011.

Sansom, Clare, "Expression of SMAD4 provides a barrier to prostate cancer," ECancerMedical Science, February 4, 2011.