A diagnosis of prostate cancer ups the risk of fatal heart attack or suicide

Prostate cancerReceiving a diagnosis of prostate cancer is a very stressful and upsetting event, so much so that some men go on to have a fatal heart attack or kill themselves.

Two pieces of research by the same study group, one conducted in 340,000 men in the US and the other in 170,000 men from Sweden, have found that the risk of dying from a heart attack is raised by 2 to 11 times in men with a diagnosis of prostate cancer.

In addition, the risk of suicide in the first year after diagnosis in American men with prostate cancer was 40% higher than the national average and the risk in the first three months 90% higher. Astoundingly, Swedish guys were twice as likely to kill themselves in the first three months after diagnosis than men who were cancer free.

Interestingly, the US study found that the risk of suicide was only raised between 1979 and 1992, before the widespread use of screening to detect prostate cancer early.  There was no link between prostate cancer and suicide once screening, known as prostate-specific antigen (PSA) testing, was being used across the board.

So does this mean that screening for prostate cancer reduces the risk of suicide after a diagnosis? The authors think so, suggesting that early screening detects less aggressive tumors that are still treatable, thus less stress inducing.

On the other hand, the use of PSA testing has long been controversial. Many men will have small prostate tumours that never do them any harm and the test itself isn’t very reliable, so screening is associated with overdiagnosis and overtreatment.

By extension, some studies reckon that routine testing for prostate cancer causes undue stress and anxiety among patients who do not understand the implications of an abnormal result.  In fact, the Swedish study did not find any difference in suicide risk between the pre-screening era and after screening had been introduced.

This post was chosen as an Editor's Selection for ResearchBlogging.org

The authors aren’t sure about this difference between their two studies, admitting “The reason for this discrepancy is unclear.” However, it could potentially be caused by the large number of nonaggressive prostate cancers diagnosed during the later years in the US study or improved access to emotional support after diagnosis come the late 80s, which might have lessened despair among patients and reduced their suicide risk.

“These results add to the complex debate of pros and cons of extensive prostate-specific antigen testing and the many nonlethal prostate cancers thus detected,” say the authors.

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Fall K et al. (2009) Immediate Risk for Cardiovascular Events and Suicide Following a Prostate Cancer Diagnosis: Prospective Cohort Study PLoS Medicine 6 (12). DOI: 10.1371/journal.pmed.1000197

Fang F et al. (2010). Immediate Risk of Suicide and Cardiovascular Death After a Prostate Cancer Diagnosis: Cohort Study in the United States JNCI Journal of the National Cancer Institute DOI: 10.1093/jnci/djp537

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When NOT to screen for cancer

Cancer screeningAnnual screening for prostate cancer may not be required in many elderly men, whereas routine screening for breast cancer should probably never have been implemented, say two separate studies published this week. These studies raise questions as to whether regular screening for common cancers is really necessary and, if so, in which groups.

In the first study, due for publication in the Journal of Urology, the authors assessed 849 men aged from 40 to 92 who had been followed up for 10 years as part of the Baltimore Longitudinal Study on Aging.

During this time period, the men had undergone an average of four tests to measure prostate specific antigen (PSA) levels. PSA level in the blood is used to screen for prostate cancer: if a man has a blood PSA level of of 4.0 ng/ml or higher, it is likely that he has prostate cancer.

The authors found that in a subgroup of men aged 75 years or older who had a PSA level of below 3.o ng/ml – well within the normal range – none died of cancer and only one developed high-risk prostate cancer.

In the US and the UK, men over the age of 50 are advised to undergo annual prostate cancer screening. The findings of this study imply that routine screening may not be needed those who are over 75 and have a normal PSA level, as such individuals are unlikely to die of or experience aggressive prostate cancer during their remaining life. Even if PSA levels indicate that a man over 75 DOES have prostate cancer, it’s likely that he’ll die of something else rather than the malignancy.  In such cases men could forgo risky therapy and avoid the nasty side effects that can seriously affect quality of life.

Speaking to Reuters, Dr H Ballentine Carter of Johns Hopkins University in Baltimore, one of the researchers contributing to the study said, “For the overwhelming majority of men over age 75, discontinuing PSA screening is probably a very safe thing to do”.

As for women, an analysis in the BMJ has highlighted the risks associated with mammography – including a high rate of false positives – and suggests that in many cases the risks inherent in routine screening for breast cancer outweigh the benefits.

The authors of this study argue that the NHS Cancer Screening Programmes leaflet about mammography, Breast screening: the facts, is unbalanced in its portrayal of the positives and negatives of screening and constitutes “one sided propaganda about breast screening”.

They suggest that the leaflet overplays the benefits of breast cancer screening, such as the possibility that screening leads to fewer mastectomies.  Various studies indicate that the number of mastectomies actually increases when screening is introduced, they point out. The authors even dispute the statement that screening saves lives, highlighting trials showing that screening does not decrease total cancer mortality.

The authors also opine that the leaflet downplays the risks of breast cancer screening, like the possibility of being overdiagnosed, which with mammography is ten times more likely than being accurately diagnosed.  “No mention is made of the major harm of screening – that is, unnecessary treatment of harmless lesions that would not have been identified without screening,” they write.

The analysis concludes that breast cancer screening is associated with less benefit and substantially more harm than previously thought and that mammography screening programmes would probably not have been initiated if the individuals who wrote the policies 20 years ago had had the evidence available today.

So should prostate cancer and breast cancer screening programmes be cut back? Doing so would avoid the consequences of false positives and would save health care providers millions of pounds in diagnostic costs.

What do you think? Would you stick to your yearly screening appointments regardless of the risk of being misdiagnosed and subjected to unneccessary treatment, just in case one day screening does catch a malignant but treatable lesion that would have otherwise been missed? Or would you rather steer clear of the hassle of screening and the stress of a false alarm?

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Researchers identify new prostate cancer marker detectable in urine

A clump of prostate cancer cellsResearchers in the US have found a new marker of the aggressiveness of prostate cancer that is detectable in the urine of men with the malignancy.  Sreekumar et al. discovered that levels of sarcosine, a common amino acid found in many biological tissues, are higher in invasive prostate cancers than in benign cancers and are detectable in the urine of affected men.

Currently, prostate cancer is detected by measuring blood levels of a marker called prostate specific antigen (PSA). The diagnosis is then confirmed by taking a tissue sample (biopsy) from the prostate using a fine needle – an uncomfortable and undignified process – and examining it under a microscope.

If further trials confirm that sarcosine levels in the urine do reflect how advanced a prostate cancer is, measurement of this marker could be used as a noninvasive way to predict the aggressiveness of a cancer and thus a patient’s prognosis.

In this study, the authors recorded all the metabolites (low molecular weight molecules produced by cells) found in samples from patients with various stages of prostate cancer, ranging from benign cancer to advanced metastatic cancer.  In total, 1,126 metabolites in 262 clinical samples related to prostate cancer were profiled.  The authors then compared the metabolites found in the various types of tumor tissues in order to unearth ‘molecular signatures’ that distinguished the different stages of prostate cancer.

In total, 87 metabolites that distinguished prostate cancer from benign prostate tissue were found, and the levels of six of these metabolites were even higher in metastatic cancer than in any other stage of disease.  Sarcosine, an N-methyl derivative of the amino acid glycine, was highly increased in metastatic samples and, importantly, was undetectable in the benign samples.

The authors then tested out what happened when they eliminated the enzyme glycine-N-methyl transferase, which is crucial for the production of sarcosine from its precursor glycine.  The invasive properties of prostate cancer cells in culture were attenuated when this enzyme, and thus sarcosine, was absent. Addition of sarcosine to benign prostate epithelial cells or knockdown of the enzyme that is responsible for sarcosine degradation caused noncancerous cells to become invasive. Taken together, these findings suggest that not only is sarcosine a marker of cancer aggressiveness, it also has a role in endowing a cancer with malignant properties.  Components of the sarcosine pathway may thus serve as new targets in the development of drugs that combat prostate cancer metastasis.

Lastly, the authors measured levels of sarcosine in urine specimens from individuals who had been definitively diagnosed with prostate cancer on the basis of PSA levels and prostate biopsy and compared these results with those from individuals who were biopsy negative.  Levels of sarcosine were significantly higher in the urine of men with prostate cancer than in those without, confirming that measurement of sarcosine in the urine may act as an indicator of prostate cancer.

Senior study author Dr Arul Chinnaiyan told The Independent: “One of the biggest challenges we face in prostate cancer is determining if the cancer is aggressive. We end up over treating our patients because physicians don’t know which tumours will be slow-growing. With this research, we have identified a potential marker for the aggressive tumours.”

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Sreekumar A et al. (2009) Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression Nature 457 (7231): 910-914 DOI: 10.1038/nature07762

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So you won’t go blind, but you might get prostate cancer

This one's a myth. You should be worried about your prostate gland instead.
This one's a myth. You should be worried about your prostate gland instead.

Although the schoolyard rumours that masturbation causes blindness or hairy palms aren’t true, a new study published in BJU International has found that too much playing solo in your twenties and thirties can increase the risk of prostate cancer.

The study of more than 800 men found that a high level of sexual activity or masturbation before the onset of middle age was associated with subsequent development of prostate cancer.

The authors suggest that the elevated levels of sex hormones some men experience in their twenties and thirties could be responsible for both a high sex drive and a high risk of prostate cancer later in life.

This British study retrospectively studied the sexual habits of 431 men who had been diagnosed with prostate cancer before the age of 60 and compared their reported behaviour with that of 409 healthy controls.

The authors found that men with prostate cancer were more likely to be very sexually active in their twenties and thirties – that is, had intercourse or masturbated 20 times a month or more – than were controls.  In fact, 40% of the men who had prostate cancer  were categorized as being very sexually active in their twenties compared with 32% of men in the control group. This pattern pretty much persisted throughout the men’s thirties and forties, and the differences in sexual activity evened out in their fifties.

Men with prostate cancer were also more apt to masturbate frequently than were men in the control group, with the greatest difference observed when the men were in their twenties (34% versus 24%) and thirties (41% versus 31%).

“Overall we found a significant association between prostate cancer and sexual activity in a man’s twenties and between masturbation and prostate cancer in the twenties and thirties. However there was no significant association between sexual activity and prostate cancer in a man’s forties”, said lead author Dr Polyxeni Dimitropoulou.

“A possible explanation for the protective effect that men in their fifties appear to receive from overall sexual activity, and particularly masturbation, is that the release of accumulated toxins during sexual activity reduces the risk of developing cancer in the prostate area. This theory has, however, not been firmly established and further research is necessary.”

Prostate cancer is the most common cancer in men in the UK, accounting for nearly a quarter of all new male cancer diagnoses. Cancer Research UK estimates that one man is diagnosed with prostate cancer every 15 minutes in the UK.

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Dimitropoulou P et al. (2009) Sexual activity and prostate cancer risk in men diagnosed at a younger age. BJU International 103 (2): 178-185 DOI: 10.1111/j.1464-410X.2008.08030.x

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Do common pain medications mask signs of prostate cancer?

A study recently published in the journal Cancer has suggested that common painkillers such as paracetamol and aspirin might affect blood levels of a marker commonly used to diagnose prostate cancer.

In this study, Singer et al. examined levels of prostate specific antigen (PSA) in the bloodstream of 1,319 men aged over 40 years. PSA is a protein produced in the prostate gland. Blood levels of PSA will be minuscule in healthy men, but raised levels often indicate the presence of prostate cancer. If a simple blood test detects serum levels of PSA higher than a specific threshold (4 ng/ml to be exact), your doctor will be booking you in for a digital rectal examination with a prostate cancer specialist faster than you can say “He wants to stick his finger where?!”

In addition, study participants were asked how often they took analgesic drugs classed as non-steroidal anti-inflammatory drugs (NSAIDs) – common types being aspirin and ibuprofen – or the drug acetaminophen, which you’ll probably be familiar with as paracetamol. NSAIDs and acetaminophen act as painkillers by reducing inflammation. Given that inflammation in the prostate has been implicated in the development of prostate cancer, the authors of this study wanted to find out whether NSAIDs or acetaminophen affected the risk of prostate cancer in men who took these drugs.

The results of this study showed that serum levels of PSA in men who took NSAIDs or acetaminophen “nearly every day” were considerably lower than levels in men who did not take either drug. Seeing as this study didn’t then follow these men for several years to find out whether there were fewer instances of prostate cancer in the men who took these analgesics than in those who didn’t, it is not clear whether this decrease in PSA levels means that the drugs reduce the risk of cancer. In fact, it it possible that NSAIDs and acetaminophen may reduce serum levels of PSA despite suspicious goings on in the prostate and thus cause doctors to miss cases of prostate cancer, which would otherwise be flagged by raised PSA levels.

So what are the implications of the study? Should men chew down aspirin every day to prevent prostate cancer, or would they make detection of the malignancy more difficult for their doctor by doing so? Dr Eric Singer, one of the authors of this study, told Reuters news, “If you’re a guy who’s close to the upper limit of normal [in PSA levels] or would have been over the upper limit and now you’re under it because of [these drugs], that could certainly change whether or not you would be referred for a biopsy [to check for a tumor]”. He also emphasizes that these findings are preliminary and shouldn’t prompt men to change their behaviour.

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Eric A. Singer, Ganesh S. Palapattu, Edwin van Wijngaarden (2008). Prostate-specific antigen levels in relation to consumption of nonsteroidal anti-inflammatory drugs and acetaminophen Cancer DOI: 10.1002/cncr.23806

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