Obesity "Dilutes" Prostate Cancer Marker Meaning Cancers In Overweight Men Might Be Missed

Main Category: Prostate / Prostate Cancer
Also Included In: Obesity / Weight Loss / Fitness;  Cancer / Oncology
Article Date: 03 Dec 2007 - 13:00 PDT

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Prostate cancer may be present in obese men even if they have low concentrations of prostate specific antigen (PSA) because the large volumes of plasma associated with being overweight mean PSA is diluted more in their circulation than in normal men, according to a study published in the Journal of the American Medical Association.

Obesity is known to be a hindrance to accurate cancer detection for several reasons. It makes physical examination more difficult and can affect the accuracy of imaging or other diagnostic tests. However, it may also affect cancer detection through biological mechanisms by altering the production or assessment of serum markers used to identify cancers. PSA is one such marker.

Prostate cancer screening and detection relies heavily on measurement of PSA concentrations in the blood, with measurements above 5 ng/mL generally considered indicative of undiagnosed cancer. But this technique is compromised by any factor that decreases PSA concentration in the circulation, and obesity is one of these. Several studies have already found that obese men have lower PSA concentrations than non-obese men. But what mechanism underlies this difference in unknown.

Several theories have been put forward: obese men frequently show lower and rogenic activity than normal-weight men, so they may simply be producing less of the substance, even if a cancer is present. But an alternative explanation is that the larger plasma volumes in obese men actually dilute the serum components therefore artificially lowering serum PSA levels. To investigate whether large plasma volumes underlie obese men's lower PSA measurements, Dr Lionel Bañez and colleagues from across Canada and the USA examined three cohorts of men with prostate cancer and looked at the relation between body-mass index (BMI), PSA measurements, and plasma volume.

The researchers identified all men who had undergone radical prostatectomy for prostate adenocarcinoma over a period ranging from the mid 1990s to 2006 from the Shared Equal Access Regional Cancer Hospital database, Duke University 's Prostate Center database, and the Brady Urological Institute at Johns Hopkins Hospital . Men with lymph-node positive disease were excluded, as were those for which no information on BMI was available. Preoperative BMI was calculated and the researchers made estimates of body surface area and total circulating plasma volume for all patient records, adjusting for cancer-related variables that may affect PSA concentration.

In the final study population of 13 734 men, it was established that men with a BMI of 35 or greater had 21% to 23% larger plasma volumes relative to normal-weight men and had lower preoperative PSA concentrations. Men in the most obese group had 11% to 21% lower serum PSA concentrations than normal-weight men, in line with the 10% to 32% decreased PSA concentration seen in population-based studies of men without prostate cancer. Next, the researchers investigated whether this finding could be explained by the fact that obese men make less PSA or whether there are alternative explanations for the lower tests of these men.

Overall, the PSA mass (the amount of PSA in the blood at the time the PSA measurement is done) did not change significantly with increasing BMI suggesting that the lower PSA measurements in obese men were a result of the diluting effect of larger plasma volumes. However, the researchers comment that, because obesity is associated with numerous changes in hormone production and effects, it remains possible that markers for several hormone-related tumours including prostate, endometrial, and breast cancer, "may be dually affected in obese individuals by both hemodilution and altered hormonal stimulation", although they concede that "in the case of PSA, the current data suggest that hemodilution predominates and that hormonal effects are rendered negligible."

Lower PSA values among obese men may have clinical relevance because they may result in fewer obese men undergoing prostate biopsy, leading to fewer cancers detected among this group. And, explain the researchers, "because cancer is generally a progressive process, some of these undetected cancers will continue to grow and may present at a later point, when they are larger and more difficult to treat." However, Dr Bañez and colleagues conclude by speculating that the overall significance of this observation on cancer outcomes is unclear: "To what degree this may help explain the epidemiologic literature, in which obesity is associated with worse oncologic outcome among newly diagnosed men and with increased prostate cancer-specific mortality-but lower risk of diagnosis, at least in some subsets-remains to be determined," they write.

Obesity-related plasma hemodilution and PSA concentration among men with prostate cancer.
Bañez LL, Hamilton RJ, Partin AW, Vollmer RT, Sun L, Rodriguez C, Wang Y, Terris MT, Aronson WJ, Presti Jr JC, Kane CJ, Amling CL, Moul JW, Freedl and SJ. JAMA 2007; 98: 2275-80.

Cancer Research Summaries are overviews of important cancer research findings that have been reported in leading cancer publications. The Cancer Research Summaries are provided by the Cancer Media Service (CMS) in collaboration with Nature Clinical Practice Oncology.

This summary is provided by the Cancer Media Service which is operated by The European School of Oncology.

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