VASECTOMY AND RISK OF PROSTATE CANCER
The weight of evidence shows no association between a vasectomy and the risk of prostate cancer. However, there has been concern that a risk might exist in subgroups such as men with a family history of prostate cancer, men who undergo the procedure at a younger age, or that risk might develop over a longer period than studied. A recent study addresses these issues. Approximately 1000 men diagnosed with prostate cancer were matched with over 900 controls. The prevalence of vasectomy was similar in the cases and controls (36.2% and 36.1%) and thus no association was found. In addition there was no association between prostate cancer and age at vasectomy, years elapsed since the procedure, or the calendar year of the vasectomy. It was concluded that prostate cancer is not an issue associated with having a vasectomy.
Holt SK, Salinas CA, Stanford JL. Vasectomy and the risk of prostate cancer. J Urol 2008 Dec;180(6):2565-7

GREEN TEA AND PROSTATE CANCER RISK
A large and long-term prospective follow-up study concerning the consumption of green tea and the risk of prostate cancer has just been reported. Over 49,000 Japanese men were included in two cohorts recruited in 1990 and 1993 and followed until the end of 2004. Green tea consumption was determined with a questionnaire. Green tea was not associated with the occurrence of localized prostate cancer but a significant protective result was observed for the risk of advanced cancer. When men drinking 5 or more cups a day were compared with those consuming less than one cup per day, a reduced relative risk of advanced cancer of approximately 50% was found that achieved statistical significance. This result was adjusted for confounding from intake of fruits, green and yellow vegetables, dairy food, soy food, and genistein consumption. The authors comment that these results are supported by many animal studies and suggest the next step should be a clinical trial in humans.
Kurahashi N et al., 2008. Green tea consumption and prostate cancer risk in Japanese men: a prospective study. Am J Epidemiol. Jan.1;167(1):71-7

TRANS-FATTY ACIDS AND RISK OF PROSTATE CANCER
Recognition of the adverse effects of trans-fatty acids has reached federal and local government levels with unprecedented moves in the direction of making these fats illegal under certain circumstances. Those who have studied chemistry will recall that the cis and trans involve different geometrical arrangements around the carbon-carbon double bond. The trans-fatty acids are for the most part foreign molecules to human biochemistry and when incorporated into cell membranes have many adverse effects. Their origin as a significant component of human food was purely commercial—longer shelf life and the option of manufacturing a solid fat such as the classical margarine. They were in fact an inadvertent product of the hydrogenation process. Thus over a short period, people in the developed countries went from eating only traces of such molecules to embracing them in large amounts as part of what they were led to believe was a healthy diet, a view actively encouraged by practically any so-called health authority one cares to mention. After all, this was the ideal way to avoid saturated fats and margarine which, while high in trans-fats, was viewed as a heart-healthy butter substitute. The realization that this was all dangerous nonsense must have come a somewhat of a shock to those who had or have implicit faith in expert opinion.

A recent study from Harvard Medical School and Brigham and Woman's Hospital has examined the hypothesis that trans-fats are related to prostate cancer risk. This hypothesis was in part based on studies indicating that the trans-fats increase systemic inflammation and insulin resistance, both of which may play a role in prostate carcinogenesis. These fatty acids also interfere with transcription genes that may be important in prostate cancer initiation and progression. They conducted a prospective case-control study nested within the Physicians' Health Study. A 13-year follow-up was involved. It was found that blood levels of two trans-fatty acids were associated with an increased risk of non-aggressive prostate tumors. When the top and bottom quintiles of intake were compared, the relative risk was more than double for total trans-fatty acid intake and approximately double for each of the two acids that were implicated (oleic and linoleic). The authors point out that this type of tumor represents a large proportion of prostate cancer detected using PSA screening and that these finding may have implications for prostate cancer prevention.
Chavarro JE, Stampfer MJ, Campos H, Kurth T, Willett WC, Ma J. A prospective study of trans-fatty acid levels in blood and risk of prostate cancer. Cancer Epidemiol Biomarkers Prev 2008 January;17(1):95- 101

Cruciferous vegetables in general and broccoli in particular seem to come up rather frequently in studies of diet and disease. Neither are probably top choices in North America for the vegetable portion of meals. However, this study found benefit for only on serving per week, which is not really an overkill in broccoli consumption. There is another option, albeit unproven by proper studies, and that is the cruciferous vegetable concentrate available in capsule form. But of course, there is no assurance that this extract contains the ingredients that are actually active in cancer prevention. Studies that will settle that question will probably never be conducted, given that vegetable extracts are not patentable. A compromise is to eat that one serving of broccoli or cauliflower or both per week and to play it safe take extract capsules as well. For those who do not like broccoli or cauliflower, experimenting with sauces such as cheese sauces or a rich Hollandaise sauce is suggested as a way of enhancing the palatability of these vegetables.
Kirsh VA et al., 2007. Prospective study of fruit and vegetable intake and risk of prostate cancer. JNCI Cancer Spectrum. 99(15):1200-1209

RISK FACTORS FOR PROSTATE CANCER. NEW RESULTS FROM THE HEALTH PROFESSIONAL'S FOLLOW-UP STUDY
This study started in 1989 and the database has been updated every four years. Initially the cohort consisted of over 51,000 male health professionals ages 40-75. Giovannucci et al have recently reported the latest results on risk factors for prostate cancer derived from this study. With regard to incidence of the disease, only family history of prostate cancer, being African- American, or consuming alpha-linolenic acid had positive associations. In addition, tomato sauce consumption was inversely related, i.e. low consumption was a positive risk factor. Only two of these risk factors are modifiable. The common source of alpha-linolenic acid is flax seeds or oil. Some consume one or the other of these for the purpose of increasing the omega-3 fatty acid intake, but the important omega-3 acids appear to be the longer chain acids such as EPA and DHA, and human biochemistry is very inefficient in the conversion. Thus fish oil or purified EPA and DHA appear to be better choices than alpha-linolenic acid quite apart from the apparent risk of prostate cancer. For fatal prostate cancer, the positive risk factors were cigarette smoking, excessive weight (BMI), family history, height, total energy consumption, and calcium intake. Physical activity was inversely related. Only for high calcium intake was there a close correspondence for positive associations between high-grade cancer (Gleason equal to or greater than 7), and advanced or fatal cancer. Tomato sauce was protective for non-advanced and low-grade (Gleason equal to or less than 6) cancers. Thus the authors point out that reducing prostate cancer mortality through lifestyle and diet may generally be more feasible than preventing its occurrence.

It is interesting that high intakes of calcium keep turning up in prostate risk studies. Men need to worry about their total intake from supplements, diet and anti-acids containing calcium carbonate. In this latest study, the threshold for increased risk from calcium intake occurred around 1200 mg/day. Calcium carbonate, the active ingredient in popular anti-acids, contains 40% elemental calcium. Thus the extra-strength 750 mg tablet contains 300 mg of calcium.
Giovannucci E et al., 2007. Risk factors for prostate cancer incidence and progression in the health professionals follow-up study. Int J Cancer. 121(7):1571-1578

ZINC INTAKE AND PROSTATE CANCER RISK
Zinc is an essential mineral in human biochemistry and acts as a cofactor for more than 70 enzymes. The recommended daily intake for men is 11 mg/day and high doses (> 150 mg/day) may reduce the immune function. Studies that found lower zinc concentrations in prostate cancer tissue as compared to normal prostate tissue have encouraged the notion that supplementation with zinc is beneficial in this context. A recent study from Italy does not support this notion and in fact finds increased risk. In a case control study based on assessment of dietary intake, the cut- point for low intake was 9.93 mg/day and for high intake, (fifth quintile) > 15.65 mg/day. For the comparison between the lowest and highest quintiles, a 56% increase in risk of prostate cancer was found after correcting for age, education, physical activity, family history of prostate cancer, BMI and total energy intake. These results are consistent with those of Leitzmann et al who found increased risk of prostate cancer associated with large doses (> 100 mg/day) over long periods (> 10 years).

Many popular multivitamin preparations contain approximately 15 mg per tablet or capsule and it is not uncommon for someone to take two a day. Thus in view of this recent study, there is the potential for increasing the risk of prostate cancer from this source alone.
Gallus S et al., 2007. Dietary zinc and prostate cancer risk: a case-control study from Italy. Eur.Urol. 52(4):1052-1056
Leitzmann MF et al., 2003. Zinc supplement use and risk of prostate cancer. JNCI Cancer Spectrum. 95(13):1004-1007

Prostate cancer risk may be raised by high cholesterol
MILAN, ITALY. Prostate cancer has been directly linked to high cholesterol for the first time in recent research from Italy. Limited evidence has previously suggested a link, but it is now strongly supported by findings from a team at the Istituto di Ricerche Farmacologiche Mario Negri. They found a statistically significant direct relationship between the two conditions after analysing the self-reported medical histories of men under the age of 75 with and without prostate cancer. The 1,294 men with prostate cancer and 1,451 comparable men with non-cancerous conditions were recruited from Italian hospitals between 1991 and 2002, and interviewed using structured questionnaires. High cholesterol levels in this study were classified as a total blood cholesterol level over 200 mg/dL (5.1 mmol/L). Participants with prostate cancer were about 50 per cent more likely to have high cholesterol than the controls. The association was somewhat stronger for men whose high cholesterol levels had been diagnosed before the age of 50 and for men over 65, in whom there was an 80 per cent greater likelihood of high cholesterol levels. The absence of an association between prostate cancer and 10 other medical conditions indicates that the relationship found here between prostate cancer and high cholesterol is real. The Italian researchers also found that prostate cancer patients were 26 per cent more likely to have suffered from gallstones. The link was not statistically significant, but gallstones are often related to high cholesterol levels.

Androgens - hormones that have a role in prostate tissue and cancer - are synthesized from cholesterol, suggesting a possible biological relationship between high cholesterol and prostate cancer. Gallstones are also related to high cholesterol levels and are often composed of cholesterol. So the direct relationship found between gallstones and prostate cancer, while it was not statistically significant, suggests that a similar biological mechanism is at work. The authors add that statins may potentially be protective against prostate cancer, but the studies so far have been limited and inconclusive.
Bravi, F. et al. Self-reported history of hypercholesterolaemia and gallstones and the risk of prostate cancer. Annals of Oncology, published online April 12, 2006

Testosterone therapy may be linked to prostate cancer
SAN DIEGO, CALIFORNIA. The recent increase in the use of testosterone therapy has led to concern over prostate cancer, which is linked to high testosterone levels. A team of researchers from the University of California at San Diego Medical Center report on 20 cases of prostate cancer developing in men a few months to a few years after they began testosterone supplementation for sexual dysfunction or "rejuvenation". The average PSA (prostate-specific antigen) level of the 17 men tested before treatment was 3 nanograms per milliliter, although the range was 1 to 15. The threshold for further evaluation is usually 4. The researchers say that in these 20 patients, clinically significant prostate cancer was presumed to be related to testosterone therapy. Although the authors state that there is no conclusive evidence yet, they add that, in their opinion, men should not receive a prescription for testosterone supplementation without careful, informed consultation regarding the risks and benefits of such treatment. This is particularly relevant for those with a family history of prostate cancer. Furthermore, the authors are concerned about the high prevalence of subclinical prostate cancer and how testosterone supplementation might affect such tumors. They hope that expert guidelines will be drawn up to aid doctors in appropriately and carefully prescribing testosterone replacement to men who need it, monitoring them for potential adverse outcomes.

The article appears alongside an editorial by a urologist from Cornell University who points out "serious flaws" in the study. For example, it does not show how common the risk of prostate cancer is in men on testosterone therapy. If results from a previous study are accurate, it may be no higher than in the general population. Moreover, in this study there is a lack of pre-treatment data for many of the patients on PSA or DRE (digital rectal examination). Nevertheless, doctors need to be extremely careful before beginning testosterone therapy, he writes, and PSA and DRE testing should be performed frequently during treatment.
Gaylis, F. D. et al. Prostate cancer in men using testosterone supplementation. The Journal of Urology, Vol. 174, August 2005, pp. 534-38

Possible prostate cancer link to low-fat milk
PHILADELPHIA, PENNSYLVANIA. Several previous studies have linked dairy foods with risk of prostate cancer. The cause of the link was initially attributed to the fat content of these foods, but it may be that their calcium content suppresses the body’s production of vitamin D, a potential protective factor against prostate cancer. As dairy products are widely promoted and have certain health benefits, researchers from the Fox Chase Cancer Center investigated the link to prostate cancer using a group of men from the first National Health and Nutrition Examination Epidemiologic Follow-up Study.

They followed 3,612 men from across the US for about eight years, during which time 131 were diagnosed with prostate cancer. Food questionnaires were given at the start of the study, when the participants were, on average, 58 years of age. The men consumed an average of 13 portions per week of dairy products, varying from three to 23 portions. Calcium intake was 730 mg on average and vitamin D intake was 172 IU on average (well below the recommended daily intake of 400 IU). Analysis showed that men in the highest third for dairy intake were 2.2 times more likely to develop prostate cancer than those in the lowest third. When each food was studied separately, risk was increased with low-fat milk but not whole milk or any other dairy food. Calcium intake also increased risk by the same amount, but in further analyses only calcium from milk was significant. Calcium supplements did not increase risk.

The authors suggest that their findings support the vitamin D suppression hypothesis. They explain that the suppressive effects of the calcium from whole milk may be countered by fortification with vitamin D, but low- fat milk has a lower vitamin-D content, as it is a fat-soluble vitamin. On the other hand, prostate cancer may simply be diagnosed more in the higher social groups which tend to drink low-fat milk and are more likely to attend screening. In conclusion, the authors state that the increased risk from dairy may occur through a calcium-related pathway. They add that the link must be clarified, as both calcium and low-fat milk may be important in avoiding osteoporosis and colon cancer.
Tseng, M. et al. Dairy, calcium, and vitamin D intakes and prostate cancer risk in the National Health and Nutrition Examination Epidemiologic Follow-up Study cohort. American Journal of Clinical Nutrition, Vol. 81, May 2005, pp. 1147-54

Diabetes protects against prostate cancer
ATLANTA, GEORGIA. The possible protective effect of diabetes against prostate cancer has been investigated once more, this time in a prospective study. Earlier studies have shown a reduction in risk of 10 to 40 per cent, and some suggest that diabetes is protective only several years after diagnosis. Researchers from the American Cancer Society used data on a group of 72,670 men from the Cancer Prevention Study II Nutrition Cohort. Information on diabetes and prostate cancer was gathered in 1982, 1992, 1997, 1999 and 2001. Prostate cancer was diagnosed in 5,318 men (7.3 per cent), who tended to be older and with a higher BMI.

The researchers found that overall; diabetes reduced the risk of prostate cancer by 33 per cent once age, race, education and prostate-specific antigen testing were taken into account. However, risk was significantly increased (by 23 per cent) in the first three years after diabetes diagnosis, compared with non- diabetic men, and only began to be protective after four years. The protective effect remained consistent when stage or grade of prostate cancer at diagnosis was examined. These results are consistent with the hypothesis that diabetes is associated with reduced risk of prostate cancer but only several years after diagnosis of diabetes, say the authors. The protective effect may be due to the reduced insulin levels found in men who have been diabetic for some time, as prostate cancer has been linked to high circulating levels of insulin.

The findings in the present study are consistent with results from a Health Professionals Follow-up Study, which also found an increased risk following diagnosis of diabetes and a protective effect after several years. In this study, prostate cancer risk was lowest 10 years after diabetes diagnosis, a reduction of 46 per cent. On the other hand, a recent case-control study within the US Physicians’ Health Study found a reduction in risk of 36 per cent, but with no link to the time since diabetes diagnosis.
Rodriguez, C et al. Diabetes and Risk of Prostate Cancer in a Prospective Cohort of US Men. American Journal of Epidemiology, Vol. 161, January 2005, pp. 147-152

Selenium and prostate cancer risk
BOSTON, MASSACHUSETTS. At least five major clinical trials have concluded that higher levels of selenium (in blood or toenail clippings) are associated with a sharply reduced risk of prostate cancer. The Nutritional Prevention of Cancer (NPC) trial found that supplementing with 200 micrograms/day of selenium cuts prostate cancer risk in half. Researchers at the Harvard Medical School now weigh in with another study confirming the beneficial effects of selenium. Their study involved 22,000 healthy, male physicians who were enrolled in the study in 1982 and had blood samples taken at that time. Sufficient samples to analyze for selenium content and PSA level were available for 586 men diagnosed with prostate cancer as well as for 577 controls matched for age and smoking status.

After 13 years of follow-up the researchers concluded that study participants with a plasma selenium level of 0.12-0.19 ppm had a 50% lower incidence of advanced prostate cancer than did men with a level of 0.06-0.09 ppm. The correlation was only apparent in men with a PSA level of more than 4 ng/mL and was particularly strong for those with a baseline (1982) PSA level greater than 10 ng/mL. For these men a high selenium level corresponded to a 70% decrease in the risk of advanced prostate cancer. The researchers also observed a trend for a lower incidence of localized prostate cancer with high selenium levels, but this trend was not statistically significant. They conclude that selenium is perhaps not too effective in preventing the initiation of prostate cancer, but that it is highly effective in slowing down tumor progression. They believe that selenium acts by selectively killing off cells whose DNA has been extensively damaged, by inhibiting cellular proliferation, and by its role as a key component of glutathione peroxidase, which protects cells from peroxide damage.
Li, H, et al. A prospective study of plasma selenium levels and prostate cancer risk. Journal of the National Cancer Institute, Vol. 96, May 5, 2004, pp. 696-703
Taylor, PR, et al. Science peels the onion of selenium effects on prostate carcinogenesis. Journal of the National Cancer Institute, Vol. 96, May 5, 2004, pp. 645-47 (editorial)

Editor's comment: The evidence is now indeed overwhelming that selenium helps protect against prostate cancer. While this study concluded that the protection mainly involves slowing down tumor progression, other studies have shown that selenium also helps prevent initiation of the cancer. Thus daily supplementation with 200 micrograms of selenium should be an integral part of all supplementation programs for men.

Prostate cancer: Risk factors and prevention
UMEAA, SWEDEN. Professor Henrik Gronberg, MD of Umeaa University in Sweden presents an excellent review of current prostate cancer research. It is estimated that over 500,000 new cases of prostate cancer was diagnosed worldwide in the year 2000. The incidence varies widely from less than 2 per 100,000 in China to 137 per 100,000 among African-Americans. It is clear that there is both a genetic and lifestyle factor involved in prostate cancer risk. Japanese men, for example, have a four times greater incidence of prostate cancer if they reside in the USA than if they reside in Japan.

Several studies have found a clear association between the western lifestyle and an increased risk of prostate cancer. A high intake of fat, meat and dairy products has been found to be particularly detrimental. Consuming fried or charcoal-grilled red meat has been clearly associated with increased risk. A high intake of alpha-linolenic acid and calcium from dairy products has both been associated with higher risk. A Swedish study found that men who consumed 600 mg/day of calcium from dairy products had a 32% greater risk than those consuming 150 mg/day or less.

Smoking, degree of physical activity, and alcohol consumption have not been associated with an increased risk and neither has vasectomy.

Soybean products (soy milk or tofu) have been found to have a preventive effect as has a high intake of tomato products, lycopene, selenium, and vitamin E. Supplementation with selenium reduced risk by 66% in one study while vitamin E supplementation lowered it by 40%. A large study involving 32,400 men is currently underway to confirm the benefits of vitamin-E and selenium supplementation. Results are expected by 2013.
Gronberg, Henrik. Prostate cancer epidemiology. The Lancet, Vol. 361, March 8, 2003, pp. 859-64

IGF-1 and advanced prostate cancer
SAN FRANCISCO, CALIFORNIA. Insulin-like growth factor-1 (IGF-1) is a potent stimulator of prostate cancer cell growth. It is mostly found in the blood bound to its carrier, IGF binding protein-3 (IGFBP-3). Only the unbound form of IGF-1 has a cancer promoting effect.

A team of researchers from Harvard Medical School and the University of California has just completed a major study aimed at determining if IGF-1 and IGFBP-3 levels can predict the risk of developing advanced stage prostate cancer. Their study involved 530 patients with prostate cancer and 534 controls matched for sex and smoking status. All participants were part of the Physicians' Health Study and were between the ages of 40 and 84 years at enrollment in 1982. Almost 15,000 of the men provided blood samples that were stored for future analysis. By the end of 1995, 786 cases of prostate cancer had been diagnosed among the 14,916 participants (5.2%). Sufficient blood plasma for IGF-1 and IGFBP-3 analysis was available for 530 of the cases and their matched 534 controls. The diagnosis of prostate cancer was made an average of 9 years after the drawing of the blood samples.

The researchers observed a strong association between IGF-1 and IGFBP-3 levels and the risk of advanced prostate cancer, but found no association with early stage disease. They found that men with IGF levels in the highest quartile had a 5.1 times higher risk of later developing advanced stage prostate cancer than did men in the lowest quartile. Men with IGFBP-3 levels in the highest quartile, on the other hand, had a 5 times lower risk of later advanced stage cancer (OR=0.2). Advanced stage prostate cancer was defined as stage C (extraprostatic, but no evidence of distant metastases) or stage D (distant metastatic or fatal). About 10% of the total 530 cases were stage D. The researchers speculate that IGF- 1 not only stimulates tumour initiation and growth, but may also facilitate invasion and metastases. They conclude that measurement of IGF-1 and IGFBP-3 levels may predict the risk of advanced stage prostate cancer years before the cancer is actually diagnosed and may thus be helpful in aiding decision making about treatment.
Chan, June M., et al. Insulin-like growth factor-1 (IGF-1) and IGF binding protein-3 as predictors of advanced-stage prostate cancer. Journal of the National Cancer Institute, Vol. 94, July 17, 2002, pp. 1099-1106
Chan, June M. Insulin-like growth factor-1 (IGF-1) and IGF binding protein-3 as predictors of advanced- stage prostate cancer. Journal of the National Cancer Institute, Vol. 94, December 18, 2002, pp. 1893-94

Sun avoidance increases cancer risk
NEWPORT NEWS, VIRGINIA. There is ample evidence that lack of sun exposure increases the risk of many types of cancer. The mortality rates for breast cancer, prostate cancer, colon cancer, ovarian cancer, and non-Hodgkin lymphoma are twice as high in the northeastern part of the US as in the southwest. Dr. William Grant, PhD, an independent American researcher, now reports additional evidence indicating the eight more cancers are associated with lack of exposure to UV-B radiation (sunshine!). Dr. Grant found a clear inverse correlation between UV-B exposure and mortality from bladder, kidney, lung, pancreatic, stomach, rectal, esophageal cancers and cancer of the corpus uteri. He estimates that over 21,000 white Americans, 1400 African Americans, and 500 people from Asian and other minorities die prematurely every year from cancer because they don't get enough sunshine.
Dr. Grant and most other researchers in the field believe that the lack of sun exposure leads to a vitamin- D deficiency, which is known to be implicated in the progression of many cancers. Vitamin D is formed in the skin when it is exposed to sunlight. Vitamin D formation is totally inhibited by sunscreens and most clothing. Dr. Grant points out that winter time UV-B levels in Boston are insufficient to promote vitamin D synthesis in the skin. He advocates prudent sun exposure when it is available and vitamin D supplementation when it is not. Editor's Note: If lack of sun exposure is a problem in northern USA then it is obviously even more of a problem in Canada. Researchers at the University of Toronto recently concluded that Canadians need to supplement with 4000 IU/day of vitamin D when they are not exposed to sunshine.
Grant, William B. An estimate of premature cancer mortality in the U.S. due to inadequate doses of solar ultraviolet-B radiation. Cancer, Vol. 94, March 15, 2002, pp. 1867-75

• A total testosterone level below 250 nanograms/mL is associated with decreased sexual function and osteoporosis.
• It is possible that as many as 5 to 50 per cent of older men would be candidates for testosterone replacement therapy.
• Most studies have shown a small increase in lean body mass and bone mineral density and a reduction of fat mass with testosterone replacement.
• It is possible that testosterone replacement may be favourable as far as heart disease is concerned, but unfavourable in regard to prostate cancer.
• Further studies are urgently required to determine if testosterone replacement therapy increases the risk of prostate cancer and benign prostatic hypertrophy (enlarged prostate). It is also possible that it could increase the level of prostate specific antigen (PSA) with the possible consequence of unnecessary biopsies and surgery.
• If testosterone replacement therapy is warranted it should be administered in the form of a gel or patch.

Report of National Institute on Aging Advisory Panel on Testosterone Replacement in Men. Journal of Clinical Endocrinology and Metabolism, Vol. 86, October 2001, pp. 4611-14

Calcium and prostate cancer
BOSTON, MASSACHUSETTS. Several studies have found that a high intake of calcium from dairy products increases the risk of prostate cancer. Other studies have found no such correlation. Now researchers at the Harvard Medical School weigh in with the results of a major study that confirms the correlation. The study involved 20,885 male American physicians who were enrolled in 1984. During 11 years of follow-up 1012 of the men developed prostate cancer including 411 cases of advanced prostate cancer. The physicians completed food frequency questionnaires to determine their intake of calcium- containing dairy products (whole milk, skim milk, cheese and ice cream). About 57 per cent of the calcium obtained from dairy products originated from skim milk which contains 307 mg of calcium per serving (8 oz glass). A thorough statistical analysis of the data collected showed that men who consumed more than 600 mg/day of calcium (equivalent to two glasses of skim milk) had a 32 per cent greater risk of developing prostate cancer, after adjusting for other potential risk factors, than did men who consumed 150 mg/day of calcium or less.
The researchers believe that a high intake of calcium suppresses the synthesis of 1,25-dihydroxyvitamin D-3, an important hormone believed to be protective against prostate cancer. They point out that another large study found that calcium from supplements also increases prostate cancer risk.
Chan, June M., et al. Dairy products, calcium, and prostate cancer risk in the Physicians' Health Study. American Journal of Clinical Nutrition, Vol. 74, October 2001, pp. 549-54

Prostate cancer linked to omega-3 fatty acid deficiency
SEOUL, KOREA. There is growing evidence that omega-6 polyunsaturated fatty acids have tumor-promoting effects while omega-3 fatty acids inhibit cancer proliferation. A recent study found an abnormally high concentration of the omega-6 fatty acid, arachidonic acid, in prostate tumors.

Researchers at the Korea Institute of Science and Technology now report that men with prostate cancer and benign prostatic hyperplasia (BPH) have markedly different ratios of omega-3 to omega-6 as compared to men with healthy prostates. Their study involved 24 men with BPH, 19 men with prostate cancer in various stages, and 21 age-matched men with normal prostates. All participants provided blood samples that were analyzed for a total of 21 different fatty acids. The researchers found no significant differences in the overall levels of saturated, monounsaturated, and polyunsaturated fatty acids. However, there was a very marked decline in the levels of EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) from the normal men to the men with BPH to the men with prostate cancer. The ratios of serum omega-3 to omega-6 polyunsaturated acids were also quite different for the three groups ranging from 0.89 for normal subjects to 0.71 for men with BPH to 0.50 for men with prostate cancer. The men with prostate cancer also had significantly higher levels of omega-6 acids than did the normal men and the men with BPH. The researchers conclude that their work supports the contention that omega-6 polyunsaturated fatty acids have a tumor-promoting effect while omega-3 acids have a protective effect. They urge further work to determine the association between the omega-3 to omega-6 ratio and prostate cancer risk.
Yang, Yoon Jung, et al. Comparison of fatty acid profiles in the serum of patients with prostate cancer and benign prostatic hyperplasia. Clinical Biochemistry, Vol. 32, August 1999, pp. 405-09

Vasectomy does not increase cancer risk
COPENHAGEN, DENMARK. A major Danish study concludes that vasectomy does not cause testicular cancer. The study involved over 73,000 Danish men who had undergone a vasectomy during the period 1977-89. During the study period, 70 men developed testicular cancer. The researchers found that the incidence of testicular cancer was no higher among vasectomized men than among the general population and that vasectomy does not cause testicular cancer nor accelerate the growth of existing testicular tumors. The researchers also found no evidence that vasectomy increases the risk of prostate cancer in the time period covered by the study. However, they do caution that prostate cancer develops very slowly and that their results regarding this cancer are therefore inconclusive at this time.
Moller, Henrik, et al. Risk of testicular cancer after vasectomy: cohort study of over 73,000 men. British Medical Journal, Vol. 309, July 30, 1994, pp. 295-9

Vasectomy does not increase cancer risk
BOSTON, MASSACHUSETTS. In 1989 researchers at the Boston University School of Medicine reported that vasectomy increases the risk of prostate cancer. Now these same researchers have concluded that vasectomy does not increase the risk of developing prostate cancer or any other cancer for that matter. They studied 355 prostatic cancer patients in comparison with 2,048 controls and found no statistically significant increase in prostate cancer rates among men who had undergone a vasectomy. They also found no evidence that the risk increases with the time elapsed since the vasectomy or with the age at vasectomy. The researchers also evaluated the risk of other cancers among vasectomized men. This study involved 4,126 men with various cancers and 7,027 controls with non-malignant conditions. They found no statistically significant difference in the rates of lung cancer, testicular cancer, pancreatic cancer, malignant melanoma, lymphoma, leukemia or cancers of the bowel, bladder or kidney among vasectomized men and non-vasectomized men. The researchers conclude that their 1989 data was insufficient to draw the conclusion that they did at the time.
Rosenberg, Lynn, et al. The relation of vasectomy to the risk of cancer. American Journal of Epidemiology, Vol. 140, No. 5, September 1, 1994, pp. 431- 38

Fatty acid intake linked to prostate cancer
CHICAGO, ILLINOIS. Scientists at the Northwestern University School of Medicine have just completed a study aimed at determining the link between fatty acid intake and the incidence of prostate cancer. Almost 15,000 male physicians participated in the study. Samples of their blood were obtained in 1982 and frozen as plasma. The scientists analyzed the plasma of 120 doctors who later developed prostate cancer and compared the results to the results for 120 matched controls who did not develop the cancer. They found that men who ate red meat at least five times a week had a 2.5 times higher risk of developing prostate cancer than did men who ate red meat less than once a week. They also found that a high concentration of alpha-linolenic acid in the plasma corresponded to a three-fold increase in the risk of developing prostate cancer. The risk increased to eight-fold in men who combined a high plasma level of alpha-linolenic acid with a low level of linoleic acid. The scientists found no significant relationship between the risk of prostate cancer and the plasma levels of the fatty acids linoleic acid, eicosapentaenoic acid, and docosahexaenoic acid.
Gann, Peter H., et al. Prospective study of plasma fatty acids and risk of prostate cancer. Journal of the National Cancer Institute, Vol. 86, No. 4, February 16, 1994, pp. 281-86

Fat intake and prostate cancer are linked
STANFORD, CALIFORNIA. Researchers at the Stanford University School of Medicine have just completed a study of the relationship between dietary factors and the incidence of prostate cancer. Their study involved 1,655 black, white, and Asian-American men who had been diagnosed with prostate cancer in the period 1987 to 1991 as well as a control group of 1,645 matched men without prostate cancer. Prostate cancer is now the most common form of cancer among North American men after skin cancer. About 178,000 new cases were diagnosed in Canada and the United States in 1993 and about 39,000 men died from the disease. The rate of prostate cancer is very high in North America, about 30 to 40 times higher than in China (Shanghai) and about 6 to 10 times higher than in Japan. The researchers conclude that men with a high intake of saturated fat (>45 grams/day), especially from red meats and dairy products, have a significantly higher risk of developing prostate cancer than do men with a lower intake (<22 grams/day). This increase in risk with increased fat intake is particularly strong for Asian-American men. The researchers also found that men with advanced prostate cancer were more likely to have eaten a high-fat diet than were men with less advanced cancer (except in the case of black men). The risk of developing prostate cancer was found to be unrelated to the intake of proteins, carbohydrates, alcohol, vitamin A, and carotenes. Physical activity level and bodyweight also showed no correlation with prostate cancer risk. Another study by Stanford researchers confirms that men who undergo a vasectomy do not increase their risk of developing prostate cancer.
Whittemore, Alice S., et al. Prostate cancer in relation to diet, physical activity, and body size in blacks, whites, and Asians in the United States and Canada. Journal of the National Cancer Institute, Vol. 87, No. 9, May 3, 1995, pp. 652-61
Hayes, Richard B. Are dietary fat and vasectomy risk factors for prostate cancer? Journal of the National Cancer Institute, Vol. 87, No. 9, May 3, 1995, p. 629-31
John, Esther M., et al. Vasectomy and prostate cancer: results from a multiethnic case - control study. Journal of the National Cancer Institute, Vol. 87, No. 9, May 3, 1995, pp. 662-69

Insulin-like growth factor 1 implicated in prostate cancer
BOSTON, MASSACHUSETTS. An international team of researchers from the Harvard Medical School, the University of Athens, and the Karolinska Institute in Sweden report that high levels of insulin-like growth factor 1 (IGF-1) in the blood are associated with an increased risk of prostate cancer. Their study involved 52 men with confirmed prostate cancer, 52 men with benign prostatic hyperplasia (BPH - enlarged prostate gland) and 52 healthy controls. Analysis of blood samples from the study participants showed that increased levels of IGF-1 corresponded to higher risks of prostate cancer. An increment of 60 nanograms of IGF-1 per milliliter of blood corresponded to an almost two-fold increase in the risk of prostate cancer. No relationship was found between IGF-1 levels and the risk of having an enlarged prostate. High levels of circulating testosterone were also associated with a higher risk of prostate cancer while higher levels of dehydroepiandrosterone sulphate (DHEAS) were associated with increased incidence of BPH. Although the researchers do not rule out that prostate cancer in itself could increase IGF-1 levels they nevertheless conclude that high IGF-1 levels may promote prostate cancer, but do not increase the risk of BPH. They also point out that previous research found a significant correlation between high IGF-1 levels and the incidence of breast cancer in women. NOTE: This study was partially funded by Monsanto, the manufacturer of bovine growth hormone (BST, Posilac). Milk from BST- treated cows has been found to contain much higher levels of IGF-1 than does normal milk.
Mantzoros, C.S., et al. Insulin-like growth factor 1 in relation to prostate cancer and benign prostatic hyperplasia. British Journal of Cancer, Vol. 76, No. 9, 1997, pp. 1115-18

New early warning signal for prostate cancer
BOSTON, MASSACHUSETTS. Researchers at the Harvard Medical School report that they have discovered a new diagnostic test which will predict men's risk of prostate cancer years before the cancer actually develops. Their discovery is part of the ongoing Physicians' Health Study which was started in 1982 and involves almost 15,000 physicians. By March 1992 520 cases of prostate cancer had occurred among the physicians. In 152 of these cases enough blood plasma had been collected in 1982 to perform analyses for the content of IGF-I (insulin-like growth factor-I). These analyses were done in 1997 and the results compared to analyses done on 152 plasma samples from 1982 obtained from physicians without prostate cancer. The researchers found that survey participants who later developed prostate cancer tended to have higher levels of IGF-I in their blood than did the controls. Men with IGF-I levels in the upper quartile (25 per cent) were found to have a 4.3 times greater risk of developing prostate cancer than did men with levels in the lower quartile of results. On average, there was a seven-year lag between the appearance of a high IGF-I level in the blood samples and the actual diagnosis of prostate cancer. The importance of high IGF-I levels was found to be particularly significant for men over 60 years of age. In this age group men with IGF-I levels in the highest quartile were almost eight times more likely to later develop prostate cancer than were men with levels in the lowest quartile. It is interesting to note that many of the men with elevated IGF-I levels who later developed prostate cancer had normal PSA levels (less than or equal to 4 ng/ml) when the blood samples were collected. The researchers conclude that IGF-I levels may serve as an early warning signal for prostate cancer in much the same way as high cholesterol levels serve as an early warning for atherosclerosis and heart disease. They also raise concern that administration of growth hormone and specifically IGF-I to delay the effects of aging in older men may increase the risk of prostate cancer. Other researchers (data still unpublished) have found an equally strong link between IGF-I levels and the risk of breast cancer and are currently investigating an association with colon cancer.
Chan, June M., et al. Plasma insulin-like growth factor-I and prostate cancer risk: a prospective study. Science, Vol. 279, January 23, 1998, pp. 563- 66
Barinaga, Marcia. Study suggests new way to gauge prostate cancer risk. Science, Vol. 279, January 23, 1998, p. 475

High calcium intake linked to prostate cancer
BOSTON, MASSACHUSETTS. Several studies have found a link between a high consumption of milk and cheese and the risk of prostate cancer. Now researchers at the Harvard Medical School report that men with a high calcium intake have a higher risk of developing prostate cancer. Their study began in 1986 and included over 47,000 male health practitioners. The participants completed food frequency questionnaires in 1986, 1988, 1990, 1992, and 1994. Between 1986 and 1994 a total of 1792 cases of prostate cancer were diagnosed among the men with 423 of the cases being of an advanced nature. After adjusting for other factors affecting prostate cancer risk the researchers concluded that men with a calcium intake of 2000 mg/day or more have a 2.97 times higher risk of developing advanced prostate cancer and a 4.57 times higher risk of developing metastatic prostate cancer than do men with an intake of 500 mg/day or less. Both calcium from food and calcium from supplements increased the risk. Milk consumption increased the risk of prostate cancer significantly with men drinking more than two glasses per day having a 60 per cent higher risk of advanced prostate cancer and an 80 per cent higher risk of metastatic prostate cancer than did men who did not consume milk.

The researchers also found that fructose protects against the development of prostate cancer. Men who consumed more than 70 grams/day had half the risk of developing advanced prostate cancer than did men who consumed only 40 grams/day or less. The main sources of fructose in the study were fruits, carbonated beverages, and sweet bakery products. A high fruit intake as such was also found to be protective with men consuming five servings a day having a 37 per cent lower risk of advanced prostate cancer than men who only consumed one serving a day or less. The researchers speculate that calcium interferes with the formation of 1,25-dihydroxycholecalciferol, the biologically active form of vitamin D which has been found to suppress the development of prostate tumors. Somewhat surprisingly, they did not find any relationship between prostate cancer risk and vitamin D intake from foods or supplements between the range of less than 150 IU/day to more than 800 IU/day. They conclude that increased fruit consumption and avoidance of a high calcium intake by middle-aged and older men may reduce the risk of prostate cancer.
Giovannucci, Edward, et al. Calcium and fructose intake in relation to risk of prostate cancer. Cancer Research, Vol. 58, February 1, 1998, pp. 442- 47

Prostate cancer - Is it mainly because of the meat?
CHARLOTTESVILLE, VIRGINIA. Prostate cancer is now the most commonly diagnosed cancer among American and European men. It is also common in Eastern countries, but the incidence of fatal, metastatic prostate cancer is much lower there. This suggests that some dietary or environmental factor is involved in determining whether prostate cancer spreads to other organs or not. Researchers at the University of Virginia Cancer Center believe they have uncovered an important clue to the puzzle. Their experiments have shown that arachidonic acid, an omega-6 fatty acid mainly found in meat and animal products, stimulates the growth of prostate cancer cells through the production of a metabolite, 5-HETE (5-hydroxyeicosatetraenoic acid). The researchers found that 5-HETE is essential for the survival of prostate cancer cells and that these cells are completely eradicated (in vitro) in a few hours by blocking the production of 5-HETE. They conclude that a high intake of dietary fats accelerates the progression of prostate cancer and that arachidonic acid is intimately involved in this process. They also suggest that drugs which inhibit the formation of 5-HETE may prove useful in the battle against prostate cancer.
Ghosh, Jagadananda and Myers, Charles E. Inhibition of arachidonate 5- lipoxygenase triggers massive apoptosis in human prostate cancer cells. Proceedings of the National Academy of Sciences USA, Vol. 95, No. 22, October 27, 1998, pp. 13182-87

Surprising risk factors for prostate cancer
BOSTON, MASSACHUSETTS. Prostate cancer is the most prevalent cancer among men and it is becoming increasingly clear that environmental and cultural factors are intimately tied in with the incidence of the disease. Researchers at the University of Massachusetts Medical School have just released a major study in which they compare the mortality rate from prostate cancer in 59 countries with a variety of environmental, dietary, and socioeconomic factors. They conclude that a high overall calorie (energy) intake, a high intake of total fat and animal products (specifically milk, meat and poultry), living in an affluent society, and having good access to medical care are associated with an increased mortality from prostate cancer. On the other hand, living in relative poverty (country with low GNP), eating lots of cereals, soybeans, nuts and oilseeds, and consuming fish is strongly correlated with a lower rate of death from prostate cancer. Thus a high intake of cereals was associated with a 31.4 per cent lower mortality and a high intake of animal products associated with a 23.8 per cent higher mortality. Milk consumption, but not butter and cheese, was found to be very strongly related to increased prostate cancer mortality, while the consumption of soybean-based products (soymilk, tofu, tempeh and miso) was found to be strongly related to decreased mortality. Members of the Brassica family of vegetables (kale, cauliflower, brussel sprouts, kohlrabi and broccoli) were also found to be highly protective as were breads containing flaxseeds, rye and buckwheat flour.
Hebert, James R., et al. Nutritional and socioeconomic factors in relation to prostate cancer mortality: a cross-national study. Journal of the National Cancer Institute, Vol. 90, November 4, 1998, pp. 1637-47

Diet and prostate cancer
MONTEVIDEO, URUGUAY. Prostate cancer is the second most common cancer in Uruguay and mortality rate has increased by 77 per cent between 1953 and 1991. Researchers at the National Cancer Institute in Montevideo believe that diet and other environmental factors may be linked to prostate cancer risk and have just released the results of a study that strongly supports this contention. Their study involved 175 patients with prostate cancer and 233 controls. Both patients and controls had face-to-face interviews with researchers and also filled out detailed questionnaires which covered family history of cancer, sociodemographic variables, height and weight, alcohol and tobacco consumption, and usual diet. Analysis of the collected data showed that a high total energy intake, and a high intake of total fat, red meat (beef and lamb) and desserts (rice pudding, custard, cake, marmalade and jam) were associated with an increased risk of prostate cancer. A high intake of vegetables, fruits, and vitamins C and E was found to significantly decrease the risk. After adjusting for other risk factors the researchers conclude that men with a high intake of vitamin C (greater than 162 mg/day) reduce their risk of prostate cancer by 60 per cent as compared to men with a low intake (less than 86 mg/day).
Deneo-Pellegrini, H., et al. Foods, nutrients and prostate cancer: a case- control study in Uruguay. British Journal of Cancer, Vol. 80, No. 3/4, May 1999, pp. 591-97

Prostate cancer risk and diet
MAASTRICHT, THE NETHERLANDS. Many studies have attempted to find an association between prostate cancer risk and diet. Some studies have found an increased risk with high intakes of animal products and calcium, others have been inconclusive. Researchers at Maastricht University have just released the results of a major study regarding diet and prostate cancer risk. The study was part of the Netherlands Cohort Study which involves 58,279 men aged 55 to 69 years when they enrolled in the study in September 1986. The men completed a 150-item food frequency questionnaire at the beginning of the study period and also provided detailed information relating to other potential risk factors for cancer. After 6.3 years of follow-up 642 of the men had developed prostate cancer. The diet of these men was compared to that of 1525 men without prostate cancer. The researchers concluded that the overall consumption of fresh meat and poultry, fish, cheese, and eggs showed no correlation with prostate cancer risk. Consumption of whole yoghurt was associated with a decreased risk, but no correlation was found between calcium intake and prostate cancer risk. There was some indication that certain cured meats (eg. sausages) were associated with an increased risk.
Schuurman, A.G., et al. Animal products, calcium and protein and prostate cancer risk in the Netherlands Cohort Study. British Journal of Cancer, Vol. 80, No. 7, June 1999, pp. 1107-13

Testosterone levels and prostate cancer
HELSINKI, FINLAND. It is generally believed that male sex hormone levels play a role in the development of prostate cancer. Clinical studies aimed at elucidating this role have produced conflicting results and it is not clear whether elevated androgen (male sex hormone) levels are associated with an increased, decreased or normal risk of prostate cancer.
A group of Finnish researchers recently released the results of a long-term study which found no significant correlation between androgen levels and the subsequent occurrence of prostate cancer. The study involved 16,481 Finnish men (aged 18 to 78 years) who had blood samples drawn between 1966 and 1972. By 1991, 166 of the men had been diagnosed with prostate cancer. Comparing the patients' serum levels of testosterone, sex hormone-binding globulin, and androstenedione to those of 300 matched controls produced no evidence of an association between the levels of these hormones and the prevalence of prostate cancer.
The researchers did notice a direct relationship between prostate cancer incidence and testosterone levels when cases occurring within eight years of the blood sampling were excluded from the analysis. This correlation, however, was not statistically significant. They conclude that high androgen levels are not associated with an increased risk of prostate cancer in Finnish men. However, they caution that racial differences may exist in this relationship.
Heikkila, Ritva, et al. Serum testosterone and sex hormone-binding globulin concentrations and the risk of prostate carcinoma. Cancer, Vol. 86, July 15, 1999, pp. 312-15