Studies
Eggs, Poultry With Skin Raise Risk of Prostate Cancer Progression
An interesting study was published in March of this year that adds to our understanding of factors that affect prostate cancer recurrence and progression. Conducted by Erin Richman and colleagues at Harvard, it was published in the American Journal of Clinical Nutrition. These same Harvard researchers have given us other useful information in past years. This current paper by Richman was a prospective trial in which consumption of processed and unprocessed red meat, fish, poultry, and eggs was examined to see if eating any of these foods affected the risk of prostate cancer recurrence or progression.
Reference: Richman EL, Stampfer MJ, Paciorek A, Broering JM, Carroll PR, Chan JM. Intakes of meat, fish, poultry, and eggs and risk of prostate cancer progression. Am J Clin Nutr. 2010 Mar;91(3):712-21.
Data was collected from 1,294 men, already diagnosed with prostate cancer and participating in the Cancer of the Prostate Strategic Urologic Research Endeavor, who had not had recurrence or progression as of 2004-2005. These men were followed for an average of 2 years.
During the two years of the study, 127 events were observed. Events were defined as prostate cancer death, metastases, elevated prostate-specific antigen or secondary treatment.
The most important finding was that greater consumption of eggs or poultry with skin on it was associated with 2-fold increases in risk when a comparison was made between those who ate the most with the least of either eggs or chicken with skin. Men with higher prognostic risk at diagnosis, that is had a higher Gleason score, and a high poultry intake, had a 4-fold increased risk of recurrence or progression compared with men with low/intermediate prognostic risk and a low poultry intake (P for interaction = 0.003). This study did not find a connection between eating processed or unprocessed red meat, fish, or skinless poultry after prostate cancer diagnosis with prostate cancer recurrence or progression.
These data may, at least for the time being, change what we tell men with prostate cancer. I write, "for the time being" as these kinds of studies are famous for "changing their minds" as new data accumulate.
[My esteemed colleague, Steve Austin's response after reading these findings was, "I've grown leery over the years in putting too much stock in observational reports. Often the findings fall apart when intervention trials are run." Yet he wisely adds, "However, when it comes to stuff like this, a prospective observation is probably the best we'll ever do."
Of the approximately 192,280 cases of prostate cancer diagnosed in 2009, over 90%, are still in the localized or regional stages for which 5-year survival is almost 100%. In cases of distant metastases, 5-year survival drops to only 32%.
Identifying factors, which patients can change, that may affect progression of prostate cancer for the better is important. Certain foods are associated with increasing or decreasing risk of getting prostate cancer. Researchers in the past have suggested that a, "diet low in fat, high in vegetables and fruits, and avoiding high energy intake, excessive meat, excessive dairy products and calcium intake, is possibly effective in preventing PC".
These studies generally assume that the same factors that increase the risk of getting prostate cancer in the first place, will affect existing cancer similarly. The truth is that we know a lot less about dietary factors that may affect recurrence and progression.
A 2006 study reported that eating a lot of fish or tomato sauce after diagnosis decreased the risks of recurrence and progression: "Men in the highest versus lowest quartile of post-diagnostic fish consumption had a multivariate hazard ratio (HR) of progression of 0.73 - the comparable HR for tomato sauce was 0.56". In other words, the guys who ate the most fish had a 27% lower risk while those who ate the most tomato sauce had a 44% lower risk of recurrence or progression.
The Richman et al., the authors of the current study, had expected that eating processed meat or red meat, because of their high saturated fat content, would increase risk of progression. They also assumed that poultry and eggs, because they contained lower levels of saturated fat and because they contained more omega-3 fats, would lower risk. They were wrong on all counts.
They found, "no evidence of an association between processed red meat, unprocessed red meat, or fish with prostate cancer progression." They did find "an increased risk of prostate cancer progression associated with higher poultry intake that was not statistically significant." There was a, "significant 2-fold increased risk of prostate cancer progression among men in the highest quartile of egg intake compared with the lowest quartile." Translated that means that those eating an average of five and a half eggs a week were twice as likely to have their cancer return or progress compared to the guys that ate less than a single egg in a two-week period.
It was when the poultry data was broken down to compare the data from men who ate their birds skinless with men who preferred their birds with skin attached, that striking results occurred. Eating skinless poultry did not increase risk of cancer recurrence or progression, but eating poultry with skin, more than doubled the risk.
How much of this should we believe? Admittedly this study wasn't perfect; the short follow-up time produced a relatively small number of cases of recurrence or progression from which to analyze and compare data. Information on what the men ate before they got prostate cancer was not collected. Eating skinless poultry may have been a marker for those men attempting to make more aggressive dietary changes. Thus the skinless eaters may have made other changes in their life styles that could explain the effect.
A 2004 review found no association between eggs or poultry and the risk of initially getting prostate cancer. In 2007, researchers suggested that there could be different factors that promote prostate cancer after diagnosis than may have initially triggered the cancer. Still other factors may be responsible for determining how aggressive the cancer will be.
As a side note, this last study from 2007 reported that increased levels of alpha-linolenic acid in the diet were associated with higher risks of prostate cancer, a troubling piece of information. The prime source of this fatty acid is flax seed oil. Many men with prostate cancer, under the impression that flax oil fights prostate cancer, consume large quantities of flax oil. This study suggests they may be making matters worse.
This is not the first time poultry has been linked with prostate cancer. The American Institute of Cancer Research suggested a possible association between total poultry and prostate cancer in their 2007 report. A 2001 study reported an association between poultry skin and risk of metastatic prostate cancer.
The authors of this current study, Richman et al., had thought that levels of saturated fat in foods would be the main predictor of risk. Because their results do not support this idea, they have proposed an alternative explanation for their findings. Eating poultry skins may cause enough of an increase in heterocyclic amines as to change the risk of cancer recurrence.
This idea isn't new. "Others [have] suggested [an] association with higher meat intake, possibly due to heterocyclic amines and polycyclic aromatic hydrocarbons, produced during grilling or frying" with prostate cancer.
Poultry contains more heterocyclic amines than any other type of meat. This has led to some interesting theories as heterocyclic amine, "intakes were estimated to be greatest for African American males, who were estimated to consume approximately 2- and approximately 3-fold more [heterocyclic amines] than white males". This difference "may at least partly explain why prostate cancer (PC) kills approximately 2-fold more African American than white men".
This current study adds to our knowledge of specific dietary advice we might give to men who have been diagnosed with prostate cancer.
It does something else though. It gives us a very different angle from which to approach this cancer. Rather than just focusing on treatments and supplements that kill cancer cells we can also seek ways to lower heterocyclic amines. Food can be prepared in different ways to lower production of these unwanted chemicals. Bowel flora can be changed to increase break down of these chemicals before they are absorbed. Even something as simple as eating yogurt or drinking beer with meals may help. The liver can be stimulated to speed their elimination. There's more that we can do to control exposure and levels of heterocyclic amines than simply avoiding chicken skin.
Avodart May Lower Prostate Cancer Risk
"A widely prescribed drug used to shrink enlarged prostates appears to reduce the incidence of prostate cancer in men with an increased risk for the disease." » Read More
Less Advanced and Lethal Prostate Cancers in Coffee Drinkers
A recent Frontiers in Cancer Prevention Research Conference was the site of a presentation of the finding that men with a high intake of coffee have a lower risk of advanced and lethal prostate cancer.
Kathryn M. Wilson, PhD of Harvard School of Public Health and her colleagues evaluated data from nearly 50,000 participants in the Health Professionals’ Follow-Up Study. Coffee intake was assessed for 1986 and every four years thereafter until 2006.
While coffee drinking appeared to have a small protective effect on the overall risk of prostate cancer, when advanced and fatal cancers were analyzed, the risk of each was 59% lower in men who consumed the most coffee.
“Very few lifestyle factors have been consistently associated with prostate cancer risk, especially with risk of aggressive disease, so it would be very exciting if this association is confirmed in other studies,” Dr. Wilson remarked.
Editor’s note: A reduction in the risk of prostate cancer has also been associated with other foods, such as tomato products containing lycopene, green tea, and especially cruciferous vegetables like broccoli and cauliflower.
Prostate Cancer and Pomegranate Juice
A study that began in 2003 is starting to yield important information when it comes to treating men who have undergone standard treatment for prostate cancer. The findings of the study were recently presented at the 104th Annual Scientific Meeting of the American Urological Association.1
The presentation described the trial that included 48 men 60+ years old who underwent radiation therapy or surgery to treat localized prostate cancer. After treatment, the men in the study all had escalating prostate-specific antigen (PSA) levels. Men who fail initial prostate cancer treatment show a progressive PSA elevation.
A six-year follow-up of the men who drank eight ounces of pomegranate juice a day revealed that those who continued drinking the juice had lower PSA levels than those who quit drinking the juice and were no longer in the trial.2
Jon Finkel
Higher Vitamin E Levels Predict Improved Prostate Cancer Survival
An article in Cancer Research reported improved prostate cancer survival among men with high vitamin E levels.*
Participants in the ATBC study whose vitamin E levels were among the top fifth of participants were found to have a 33% lower risk of dying of prostate cancer compared to those whose levels were in the lowest fifth. Men who received vitamin E supplements in the trial and whose levels of vitamin E were highest experienced the lowest risk of prostate cancer mortality, which was 49% less than that of subjects with the lowest vitamin E levels.
When all-cause mortality was analyzed among those with prostate cancer, participants in the top fifth of serum vitamin E levels were shown to have a 33% lower risk of death over the course of follow-up, suggesting “a possible effect for alpha-tocopherol on other causes of death in men with prostate cancer.”
Dayna Dye
For some prostate tumors, ‘watchful waiting’ seems safe
Men diagnosed with early, low-risk prostate cancer face a choice about treatment. Some tumors will not grow larger, but other tumors will progress, making them candidates for surgery, radiation, or chemotherapy. A new clinical trial shows that men with low-risk prostate cancer who decided to defer treatment for almost eight years did no worse than similar men who decided to have treatment sooner.
A team from Beth Israel Deaconess Medical Center, Brigham and Women’s Hospital, and the University of California, San Francisco, analyzed medical records of more than 51,000 men enrolled in the Health Professionals Follow-up Study. Among the 3,331 men who were diagnosed with prostate cancer between 1986 and 2007, there were 342 men with low-risk tumors who chose not to have treatment in the first year. Half of those men still had not had treatment almost eight years after diagnosis.
There were few deaths from prostate cancer among the men who deferred treatment. Two percent of the men who deferred treatment died compared with 1 percent of the men with low-risk cancers who had treatment right away, a difference that was not statistically significant.
“I think it really brings some reassurance to the notion that it can be safe to defer treatment for the very low risk subset of prostate cancers,’’ said senior author Dr. Martin Sanda of Beth Israel Deaconess.
Active surveillance of patients based on prostate specific antigen screenings, repeated biopsies, and imaging tests can be used to track whether cancer is progressing, he said.
BOTTOM LINE: Men with low-risk prostate cancer who deferred treatment for a year or more fared no worse after eight years than men who chose early treatment.
CAUTIONS: The number of men who deferred treatment is small, so drawing conclusions about them should be done with caution. Patients were not randomly assigned to the waiting or immediate-treatment groups, so unknown differences among the men in the two groups might have biased the outcomes.
WHERE TO FIND IT: Journal of Clinical Oncology, Aug. 31
ELIZABETH COONEY
Selenium intake may worsen prostate cancer in some, study reports
BOSTON--Higher selenium levels in the blood may worsen prostate cancer in some men who already have the disease, according to a study by researchers at Dana-Farber Cancer Institute the University of California, San Francisco.
A higher risk of more-aggressive prostate cancer was seen in men with a certain genetic variant found in about 75 percent of the prostate cancer patients in the study. In those subjects, having a high level of selenium in the blood was associated with a two-fold greater risk of poorer outcomes than men with the lowest amounts of selenium. By contrast, the 25 percent of men with a different variant of the same gene and who had high selenium levels were at 40 percent lower risk of aggressive disease. The variants are slightly different forms of a gene that instructs cells to make manganese superoxide dismutase (SOD2), an enzyme that protects the body against harmful oxygen compounds.
The research findings suggest that "if you already have prostate cancer, it may be a bad thing to take selenium," says Philip Kantoff, MD, director of Dana-Farber's Lank Center for Genitourinary Oncology and senior author of the study that is published by the Journal of Clinical Oncology on its website now and later will be in a print journal. The lead author is June Chan, ScD, of the University of California, San Francisco.
The unexpected results are the first to raise concern about this potentially harmful consequence of taking supplemental selenium. Kantoff says, "These findings are interesting particularly in light of the recent negative results from the SELECT prevention study, which asked if selenium could protect against prostate cancer."
The new study reveals the strong interaction between selenium and SOD2 to influence the biology of prostate cancer, a finding that these investigators had shown in a previous study. The authors say the current research demonstrated that variations in the make up of the SOD2 gene dramatically alter the effects of selenium on the risk of aggressive prostate cancer.
Selenium is a mineral found widely in rocks and dirt. Small amounts of selenium are essential for health: 40 to 70 micrograms is the recommended daily intake. In recent years, supplemental selenium has been sold and promoted as a means of preventing prostate cancer, largely based on observational studies that found higher risk of prostate cancer incidence and mortality in areas of the country that are naturally low in selenium.
However, research aimed at confirming the benefits of selenium supplementation have been mixed. Recently, the SELECT study, which involved 35,000 men, was halted early when, after more than five years, it showed that the supplements didnt affect the incidence of prostate cancer.
Previous studies had found that the risk of developing prostate cancer was modified by a strong interaction between SOD2 and selenium. The new research was designed to look at the effect of this interaction on men already diagnosed with prostate cancer.
Scientists examined banked blood samples, DNA, and medical records of 489 male Dana-Farber patients diagnosed between 1994 and 2001 with localized or locally advanced prostate cancer. Their mean age was 62, and their mean PSA (prostate-specific antigen) measurement was 6.0 ng/mL. About half the men were assessed as having a good disease risk, one-third had an intermediate risk, and the remaining one-sixth were at poor risk. The researchers measured the level of selenium in the blood and, using the stored DNA, they determined the SOD2 genotype -- the specific form of the SOD2 gene carried by each patient.
Simply having a high level of selenium was associated with a slightly elevated risk of aggressive prostate cancer. But the risk was much more strongly affected by the interaction of selenium levels and whether the patient had a certain variant of the SOD2 gene. Men with the highest selenium levels and the "AA" form of the SOD2 gene were 40 percent less likely to have been diagnosed with aggressive prostate cancer than the men with same gene form but low levels of selenium.
But for men carrying the "V" form of the gene, selenium had the opposite effect. In these men, those with the highest levels of selenium in their blood were about twice as likely to have an aggressive type of prostate cancer as their counterparts with low selenium levels, says Kantoff, who is also a professor of medicine at Harvard Medical School.
The study couldnt determine whether any of the men had been taking selenium supplements or not. But the researchers noted that men in the large SELECT prevention trial had a much higher average selenium level than those in the current study. "Among the 25 percent of men with the AA genotype, having greater selenium levels may protect against aggressive disease," the authors concluded. "However, for the 75 percent of men who carry a V allele, higher selenium levels might increase the likelihood of having worse characteristics."
Therefore, they add, it is important to know which type of SOD2 gene a man has when considering the risks and potential benefits of taking selenium supplements. Additionally, the authors say the effects of the interaction between the SOD2 genotype and selenium may help explain apparently conflicting results of previous studies.
The results may seem counterintuitive to the public, who have been told for years that antioxidants can help people live longer, healthier lives with a lowered risk of cancer. However, Kantoff says, "There is some precedent to this research has suggested that antioxidants could be protective if you dont have cancer, but once you do, then antioxidants may be a bad thing."
In addition to Kantoff and Chan, other authors of the paper include William Oh, MD, Wanling Xie, PhD, Meredith Regan, ScD, and Miyako Abe, PhD, of Dana-Farber; Meir J. Stampfer DrPH, MD, of Brigham and Women's Hospital and the Harvard School of Public Health, and Irena King, PhD, of the Fred Hutchinson Cancer Research Center, Seattle.
The work was supported by grants from the National Cancer Institute and several foundations and charitable organizations.
Dana-Farber Cancer Institute (www.dana-farber.org) is a principal teaching affiliate of the Harvard Medical School and is among the leading cancer research and care centers in the United States. It is a founding member of the Dana-Farber/Harvard Cancer Center (DF/HCC), designated a comprehensive cancer center by the National Cancer Institute.
Green Tea Slows Prostate Cancer
Active compounds in green tea may slow the progression of prostate cancer, according to a new study published in Cancer Prevention Research.
The study, which was conducted at Louisiana State University, also showed that green tea might lower the incidence of prostate cancer in the first place.
The study is one of the few green tea trials that evaluated biomarkers in order to predict prostate cancer's progression, said study leader James A. Cardelli, director of basic and translational research in the Feist-Weiller Cancer Center at LSU University Health Sciences Center-Shreveport.
The biomarkers tracked were PSA (prostate specific antigen), HGF (hepatocyte growth factor), and VEGF (vascular endothelial growth factor).
The study, which used compounds of green tea polyphenols in the form of Polyphon E provided by Polyphenon Pharma, involved 26 men ages 41 to 72 who were scheduled for radical prostactectomies. For an average of about 35 days up until the day before surgery, each man took four capsules of Polyphenon E, which was equal to drinking 12 cups of normally brewed green tea.
The researchers found that the green tea compounds significantly reduced serum levels of PSA, HGF, and VEGF, with reductions as great as 30 percent in some patients.
There were few side effects, and other biomarkers were "positively affected," Cardelli said.
Referring to the LSU study and to a year-long clinical trial in Italy involving green tea polyphenols, Cardelli said, "These studies are just the beginning and a lot of work remains to be done. However, we think that the use of tea polyphenols alone or in combination with other compounds currently used for cancer therapy should be explored as an approach to prevent cancer progression and recurrence."
Selenium intake may worsen prostate cancer in some, study reports
BOSTON--Higher selenium levels in the blood may worsen prostate cancer in some men who already have the disease, according to a study by researchers at Dana-Farber Cancer Institute the University of California, San Francisco.
A higher risk of more-aggressive prostate cancer was seen in men with a certain genetic variant found in about 75 percent of the prostate cancer patients in the study. In those subjects, having a high level of selenium in the blood was associated with a two-fold greater risk of poorer outcomes than men with the lowest amounts of selenium. By contrast, the 25 percent of men with a different variant of the same gene and who had high selenium levels were at 40 percent lower risk of aggressive disease. The variants are slightly different forms of a gene that instructs cells to make manganese superoxide dismutase (SOD2), an enzyme that protects the body against harmful oxygen compounds.
The research findings suggest that "if you already have prostate cancer, it may be a bad thing to take selenium," says Philip Kantoff, MD, director of Dana-Farber's Lank Center for Genitourinary Oncology and senior author of the study that is published by the Journal of Clinical Oncology on its website now and later will be in a print journal. The lead author is June Chan, ScD, of the University of California, San Francisco.
The unexpected results are the first to raise concern about this potentially harmful consequence of taking supplemental selenium. Kantoff says, "These findings are interesting particularly in light of the recent negative results from the SELECT prevention study, which asked if selenium could protect against prostate cancer."
The new study reveals the strong interaction between selenium and SOD2 to influence the biology of prostate cancer, a finding that these investigators had shown in a previous study. The authors say the current research demonstrated that variations in the make up of the SOD2 gene dramatically alter the effects of selenium on the risk of aggressive prostate cancer.
Selenium is a mineral found widely in rocks and dirt. Small amounts of selenium are essential for health: 40 to 70 micrograms is the recommended daily intake. In recent years, supplemental selenium has been sold and promoted as a means of preventing prostate cancer, largely based on observational studies that found higher risk of prostate cancer incidence and mortality in areas of the country that are naturally low in selenium.
However, research aimed at confirming the benefits of selenium supplementation have been mixed. Recently, the SELECT study, which involved 35,000 men, was halted early when, after more than five years, it showed that the supplements didn’t affect the incidence of prostate cancer.
Previous studies had found that the risk of developing prostate cancer was modified by a strong interaction between SOD2 and selenium. The new research was designed to look at the effect of this interaction on men already diagnosed with prostate cancer.
Scientists examined banked blood samples, DNA, and medical records of 489 male Dana-Farber patients diagnosed between 1994 and 2001 with localized or locally advanced prostate cancer. Their mean age was 62, and their mean PSA (prostate-specific antigen) measurement was 6.0 ng/mL. About half the men were assessed as having a good disease risk, one-third had an intermediate risk, and the remaining one-sixth were at poor risk. The researchers measured the level of selenium in the blood and, using the stored DNA, they determined the SOD2 genotype -- the specific form of the SOD2 gene carried by each patient.
Simply having a high level of selenium was associated with a slightly elevated risk of aggressive prostate cancer. But the risk was much more strongly affected by the interaction of selenium levels and whether the patient had a certain variant of the SOD2 gene. Men with the highest selenium levels and the "AA" form of the SOD2 gene were 40 percent less likely to have been diagnosed with aggressive prostate cancer than the men with same gene form but low levels of selenium.
But for men carrying the "V" form of the gene, selenium had the opposite effect. In these men, those with the highest levels of selenium in their blood were about twice as likely to have an aggressive type of prostate cancer as their counterparts with low selenium levels, says Kantoff, who is also a professor of medicine at Harvard Medical School.
The study couldn’t determine whether any of the men had been taking selenium supplements or not. But the researchers noted that men in the large SELECT prevention trial had a much higher average selenium level than those in the current study. "Among the 25 percent of men with the AA genotype, having greater selenium levels may protect against aggressive disease," the authors concluded. "However, for the 75 percent of men who carry a V allele, higher selenium levels might increase the likelihood of having worse characteristics."
Therefore, they add, it is important to know which type of SOD2 gene a man has when considering the risks and potential benefits of taking selenium supplements. Additionally, the authors say the effects of the interaction between the SOD2 genotype and selenium may help explain apparently conflicting results of previous studies.
The results may seem counterintuitive to the public, who have been told for years that antioxidants can help people live longer, healthier lives with a lowered risk of cancer. However, Kantoff says, "There is some precedent to this – research has suggested that antioxidants could be protective if you don’t have cancer, but once you do, then antioxidants may be a bad thing."
In addition to Kantoff and Chan, other authors of the paper include William Oh, MD, Wanling Xie, PhD, Meredith Regan, ScD, and Miyako Abe, PhD, of Dana-Farber; Meir J. Stampfer DrPH, MD, of Brigham and Women's Hospital and the Harvard School of Public Health, and Irena King, PhD, of the Fred Hutchinson Cancer Research Center, Seattle.
The work was supported by grants from the National Cancer Institute and several foundations and charitable organizations.
Dana-Farber Cancer Institute (www.dana-farber.org) is a principal teaching affiliate of the Harvard Medical School and is among the leading cancer research and care centers in the United States. It is a founding member of the Dana-Farber/Harvard Cancer Center (DF/HCC), designated a comprehensive cancer center by the National Cancer Institute.
Fish Consumption Improves Survival in Prostate Cancer
Men who consume large amounts of fish have better survival from prostate cancer, according to a long-term follow-up study.*
More than 20,000 men who participated in the Physician’s Health Study answered questionnaires at enrollment in 1983 about medical history, lifestyle characteristics, and food intake, and then reported all new illnesses each year thereafter. During follow-up of 19 years, 2,161 cases of prostate cancer occurred and 230 men died of the disease.
Total fish intake was not a significant predictor of developing prostate cancer. However, consumption of fish and of fish-derived omega-3 fatty acids increased the likelihood of surviving prostate cancer. Men who ate fish at least five times per week (versus less than once per week) had a 48% lower risk of death from prostate cancer, and men with the highest fatty acid intake had a 35% lower risk.
The results suggest that fish consumption delays prostate cancer progression.
—Laura J. Ninger, ELS
(From Life Extension, March 2009)
Studies fail to settle prostate testing debate
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Resveratrol Suppresses Prostate Cancer Development
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Many prostate cancer patients receive improper or 'mismatched' therapies
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Green Tea Shown To Prevent Prostate Cancer
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