HEALTH REPORT: Statins & Prostate Cancer; Diet, Acrylamide & Cancers of the Uterus, Ovary & Breast; Dark Chocolate & Coronary Artery Function
STATINS & PROSTATE CANCER
Although the scientific data on the subject has been mixed thus far, there continues to be great interest in an unintended possible benefit of the hugely popular cholesterol-lowering drugs commonly referred to as �statins.� These drugs lower elevated cholesterol levels by blocking a key enzyme necessary for cholesterol production in the body, and have been shown to reduce the risk of heart attack and other cardiovascular events in multiple large studies. Some clinical research studies have suggested that statins may also reduce the risk of developing some cancers, perhaps due to their known anti-inflammatory effects. While the scientific jury is still definitely out on the topic of statins and cancer risk, three interesting new papers, just published in the journal Cancer Epidemiology, Biomarkers & Prevention, assess the potential clinical impact of statins on the risk of developing prostate cancer.
The first study, performed jointly by researchers from Kaiser Permanente and Harvard Medical School, reviewed the association between long-term statin use and the incidence of prostate cancer in almost 70,000 participants in the huge California Men�s Study, which was initiated in 2002 by Kaiser Permanente�s Northern and Southern California health systems. By using Kaiser Permanente�s exceptional prospective clinical database, the researchers were able to estimate the duration of statin usage by participants in this large study, as well as new diagnoses of prostate cancer in these men. A total of 888 new cases of prostate cancer were diagnosed among these study participants during the 2002 to 2004 timeframe of this clinical study. Among the men who had been taking statin drugs for less than 5 years, there was no apparent reduction in prostate cancer incidence when compared to a matched group of men who were not taking these cholesterol-lowering medications. However, among the cohort of men who had been taking statins for 5 or more years, a 28% reduction in the incidence of prostate cancer was observed. Unfortunately, this association between statins and a reduced risk in the incidence of prostate cancer only appeared among men who were also taking anti-inflammatory medications known as nonsteroidal anti-inflammatory drugs (this class of drugs includes aspirin, ibuprofen, and naproxen, among several others, many of which are now available over the counter; and the now highly restricted prescription drugs Vioxx and Celebrex).
The results of this study, unfortunately, do not confirm a favorable association between statin medications and the risk of prostate cancer, as the nonsteroidal anti-inflammatory class of drugs are known to be potent cancer preventive agents in their own right (especially for precancerous colon and rectal polyps). Another limitation of large epidemiological �observational� studies, such as this one, is that a nearly infinite number of potential variables have to be considered and accounted for. Unlike prospective, randomized clinical trials, where one matched group of study participants all receive one medication or treatment, while another matched group receives only a placebo or another alternative treatment, observational studies almost always suffer from an inescapable level of uncertainty regarding the true relationship between the variables studied (in this case, the use of statins, and their duration of use) and the outcomes observed (the incidence of prostate cancer, in this study). Separating out true �cause-and-effect� relationships from mere �associations� can be almost impossible in many of these complex studies, even when great effort is taken, as was done in this study, to try and identify all other potentially relevant variables so that they can be included in the final statistical analysis of all collected data. So, based upon this study alone, one would be hard-pressed to conclude that the use of statin drugs is associated with a significant reduction in the risk of prostate cancer.
The second study, from the Finnish Cancer Institute, reviewed all cases of prostate cancer diagnosed in Finland between 1995 and 2002, and then matched these prostate cancer cases with men of similar ages who had not been diagnosed with prostate cancer, for a total of almost 25,000 individuals. As in many countries with a socialized healthcare system, the authors were able to review the prescription records of all of the men involved in this study, including the use of statin drugs. Unfortunately, there did not appear to be any overall reduction in the incidence of prostate cancer among the men who were prescribed statin drugs. However, the risk of presenting with advanced prostate cancer appeared to be lower among men who had taken atorvastatin, lovastatin or simvastatin, but not any of the other statin drugs in use in Finland during the period of this study.
Finally, the third study, from the American Cancer Society, looked at a large database from the Cancer Prevention Study II Nutrition Cohort study. More than 55,000 men in this study were evaluated, and as with the prior two studies, looking for an association between statin use and the incidence of prostate cancer. As with the Finnish and Kaiser Permanente studies, this epidemiological study did not find any association between statin use and the incidence of prostate cancer, overall, although, as with the Finnish study, there did seem to be a modest reduction in the incidence of advanced cases of prostate cancer, at presentation, among the patients using statin medications for 5 or more years.
Taken together, these three large epidemiological studies do not appear to reveal any beneficial effect of statin medications on the risk of developing prostate cancer, although, perhaps, statins might decrease the likelihood of being diagnosed with a more advanced stage of prostate cancer. As with so many other important clinical questions, the final word on this topic awaits mature data from large, randomized, blinded, placebo-controlled clinical trials.
DIETARY ACRYLAMIDE & RISK OF CANCERS OF THE UTERUS, OVARY & BREAST
The role of dietary factors in cancer development is an area of intense interest and ongoing research. The relationship between dietary acrylamide and certain cancers has been an area of great debate, as acrylamide, which is produced by cooking and frying carbohydrate-rich foods (think french fries, potato chips, and other carbohydrate-rich snack foods�), is known to have carcinogenic properties based upon laboratory studies, although the association between acrylamide and cancer in humans, if any, is not really known.
A new study, published in the journal Cancer Epidemiology, Biomarkers & Prevention, evaluated the dietary intake of acrylamide in a large public health study that is tracking the association of diet with the incidence of cancer in the Netherlands. Almost 2,600 study participants (out of a total of more than 62,000 adult women study participants) were randomly chosen for the study of acrylamide intake and cancer risk. Combining data from dietary surveys and cancer histories in this study population, as well as the results of chemical analyses of Dutch foods for acrylamide content, this epidemiological study followed this group of women for just over 11 years. Importantly, smokers participating in this trial were identified up front, as tobacco smoke contains significant amounts of acrylamide as well. When the smokers were eliminated from the statistical results, high dietary levels of acrylamide were found to be associated with double the risk of developing uterine and ovarian cancer when compared to study volunteers with the lowest amount of acrylamide in their diet. No association between acrylamide intake and breast cancer was observed, however.
As with my previous comments regarding the limitations of �observational� epidemiological studies (including this Dutch study, which was highly dependent upon the accuracy of dietary surveys completed by study participants), whether or not the observed relationship between high acrylamide intake and cancers of the uterus and ovaries reveals a true cause-and-effect mechanism, versus a mere observational association, cannot be completely verified by studies such as these. However, there is ample high-level clinical and scientific evidence linking high-fat, high-salt, and high-carbohydrate diets with cardiovascular diseases and diabetes, and so, based upon the additive information supplied by this large, long-term public health study, it would appear prudent to limit one�s intake of these food items.
DARK CHOCOLATE & CORONARY ARTERY FUNCTION
And now for some potentially good news regarding diet and health�! A new study from Europe, just published in the journal Circulation, studied the effects of dark chocolate in patients who had previously undergone a heart transplant. Dark chocolate, unlike its fat- and sugar-loaded cousin milk chocolate, is rich in antioxidants collectively known as flavonoids. These compounds are though to interrupt the metabolic mechanisms, including inflammatory pathways, underlying the development of atherosclerosis. When the arteries that nourish the heart (coronary arteries) become severely clogged with atherosclerotic plaques, angina and heart attacks are often the result. (The progression of atherosclerotic coronary artery diseases has long been known to be accelerated in heart transplant patients, and so this group of patients is an obvious target in looking at measures that might prevent�or at least slow down�the development of atherosclerosis.)
In this small but innovative prospective, randomized, double-blind study (i.e., neither the patients nor their doctors knew who was receiving real dark chocolate versus cocoa-free �fake� chocolate), the researchers evaluated the ability of the study volunteers� coronary arteries to dilate after eating dark chocolate versus the �placebo chocolate.� Coronary artery dilation is, in itself, a measure of healthy coronary artery function, and the loss of this ability to rapidly dilate to a larger caliber when the heart muscle needs more blood flow is thought to be associated with an increased risk of developing atherosclerosis. Likewise, the researchers also measured the �stickiness� of blood cells called platelets, following ingestion of dark chocolate versus placebo chocolate. Platelets are a critical part of the body�s blood clotting mechanism. When an injury in the body occurs, these tiny cells clump together and form a plug-like matrix upon which blood clots can form. Unfortunately, when the lining of our coronary arteries become damaged by atherosclerosis, platelets can begin to stick onto these atherosclerotic plaques, which can lead to a sudden and complete blockage of the small coronary arteries. This is thought to be the mechanism whereby most heart attacks are generated, and it is the primary reason why aspirin, which impairs platelet function, is used to prevent and treat heart attacks.
In the heart transplant patients who ate dark chocolate two hours before testing, the coronary artery dilation response was much more robust than was seen in the patients who ate the placebo chocolate. In fact, there was no change in arterial dilation observed in the patients who ate the fake chocolate. Likewise, eating 40 grams of dark chocolate also reduced the �stickiness� of platelets, while the bogus chocolate had no impact at all on platelet adhesion. While this elegant research study does not prove that eating dark chocolate will reduce your chances of cardiovascular disease, including heart attacks, it does nonetheless objectively show that dark chocolate can improve the coronary arteries� ability to dilate, while also reducing the tendency of platelets to stick to damaged blood vessels. Taken together, the findings of this interesting little study suggest that dark chocolate, unlike its tastier relative, milk chocolate, may have some beneficial impact on cardiovascular function. A long-term prospective, randomized clinical trial involving non-transplant volunteers at high risk for coronary artery diseases is now needed to further assess the potential benefits (and side effects) of dark chocolate, as well as to study the optimum amount (if any) of dark chocolate that should be incorporated into a heart-healthy diet.
Disclaimer: As always, my advice to readers is to seek the advice of your physician before making any significant changes in medications, diet, or level of physical activity
Dr. Wascher is an oncologic surgeon, professor of surgery, and a widely published author. He is the Director of the Division of Surgical Oncology at Newark Beth Israel Medical Center.
Send your feedback to Dr. Wascher at rwascher@doctorwascher.net
http://www.sbhcs.com/hospitals/newark_beth_israel/mservices/oncology/surgical.html
Cancer surgeon, professor of surgery & author. Webmaster: http://doctorwascher.com | More from Robert A. Wascher, MD, FACS
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