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LE Magazine January 2004

Dietary fat intake and risk of prostate cancer: a prospective study of 25,708 Norwegian men.
The relationship between incidence of prostate cancer and intake of dietary fat and foods rich in fat was studied in 25,708 men aged 16-56 years attending a Norwegian health screening in 1977-1983. Linkage to the Cancer Registry of Norway and the Central Bureau of Statistics of Norway ensured a complete follow-up until December 31, 1992. Diet was recorded on a semi-quantitative food-frequency questionnaire at the time of screening, and 72 cases of prostate cancer were identified during follow-up. At the end of follow-up, mean age of the total study sample was 56 years (range 19-68), while mean age at diagnosis of prostate cancer was 60 years (range 47-67). No association was found between energy-adjusted intake of total fat, saturated fat, mono-unsaturated fat or poly-unsaturated fat and the incidence of prostate cancer. Significant positive associations were found for body mass index (BMI) and consumption of hamburgers/meatballs, while no association was found with consumption of frankfurters/sausages and a significant negative association with the weekly number of main meals with meat. A significantly increased risk of prostate cancer was associated with skim milk as compared to whole milk. Milk preference (skim vs. whole) was associated significantly positively with BMI. Our study of a relatively young cohort does not confirm previous case-control and cohort studies suggesting that dietary fat, especially from animal sources, is associated positively with risk of prostate cancer.

Int J Cancer. 1997 Nov 27;73(5):634-8

A prospective study of dietary fat and risk of prostate cancer.
BACKGROUND: The strong correlation between national consumption of fat and national rate of mortality from prostate cancer has raised the hypothesis that dietary fat increases the risk of this malignancy. Case-control and cohort studies have not consistently supported this hypothesis. PURPOSE: We examined prospectively the relationship between prostate cancer and dietary fat, including specific fatty acids and dietary sources of fat. We examined the relationship of fat consumption to the incidence of advanced prostate cancer (stages C, D, or fatal cases) and to the total incidence of prostate cancer. METHODS: We used data from the Health Professionals Follow-up Study, which is a prospective cohort of 51,529 US men, aged 40 through 75, who completed a validated food-frequency questionnaire in 1986. We sent follow-up questionnaires to the entire cohort in 1988 and 1990 to document new cases of a variety of diseases and to update exposure information. As of January 31, 1990, 300 new cases of prostate cancer, including 126 advanced cases, were documented in 47,855 participants initially free of diagnosed cancer. The Mantel-Haenszel summary estimator was used to adjust for age and other potentially confounding variables. Multiple logistic regression was used to estimate relative risks (RRs) when controlling simultaneously for more than two covariates. RESULTS: Total fat consumption was directly related to risk of advanced prostate cancer (age- and energy-adjusted RR = 1.79, with 95% confidence interval [CI] = 1.04-3.07, for high versus low quintile of intake; P [trend] = .06). This association was due primarily to animal fat (RR = 1.63; 95% CI = 0.95-2.78; P [trend] = .08), but not vegetable fat. Red meat represented the food group with the strongest positive association with advanced cancer (RR = 2.64; 95% CI = 1.21-5.77; P = .02). Fat from dairy products (with the exception of butter) or fish was unrelated to risk. Saturated fat, monounsaturated fat, and alpha-linolenic acid, but not linoleic acid, were associated with advanced prostate cancer risk; only the association with alpha-linolenic acid persisted when saturated fat, monounsaturated fat, linoleic acid, and alpha-linolenic acid were modeled simultaneously (multivariate RR = 3.43; 95% CI = 1.67-7.04; P [trend] = .002). CONCLUSION: The results support the hypothesis that animal fat, especially fat from red meat, is associated with an elevated risk of advanced prostate cancer. IMPLICATIONS: These findings support recommendations to lower intake of meat to reduce the risk of prostate cancer. The potential roles of carcinogens formed in cooking animal fat and of alpha-linolenic acid in the progression of prostate cancer need to be explored.

J Natl Cancer Inst. 1993 Oct 6;85(19):1571-9

Dairy products, calcium, and prostate cancer risk in the Physicians' Health Study.
BACKGROUND: A high calcium intake, mainly from dairy products, may increase prostate cancer risk by lowering concentrations of 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)], a hormone thought to protect against prostate cancer. The results of epidemiologic studies of this hypothesis are inconclusive. OBJECTIVE: We investigated the association between dairy product and calcium intakes and prostate cancer risk in the Physicians' Health Study, a cohort of male US physicians. DESIGN: At baseline, the men answered abbreviated dietary questionnaires. During 11 y of follow-up, we documented 1,012 incident cases of prostate cancer among 20885 men. We estimated dairy calcium intake on the basis of consumption of 5 major dairy products and used logistic regression to estimate relative risk. RESULTS: At baseline, men who consumed >600 mg Ca/d from skim milk had lower plasma 1,25(OH)(2)D(3) concentrations than did those consuming < or =150 mg Ca/d [71 compared with 85 pmol/L (30.06 compared with 35.64 pg/mL); P = 0.005]. Compared with men consuming < or =0.5 daily servings of dairy products, those consuming >2.5 servings had a multivariate relative risk of prostate cancer of 1.34 (95% CI: 1.04, 1.71) after adjustment for baseline age, body mass index, smoking, exercise, and randomized treatment assignment in the original placebo-controlled trial. Compared with men consuming < or =150 mg Ca/d from dairy products, men consuming >600 mg/d had a 32% higher risk of prostate cancer (95% CI: 1.08, 1.63). CONCLUSIONS: These results support the hypothesis that dairy products and calcium are associated with a greater risk of prostate cancer.

Am J Clin Nutr. 2001 Oct;74(4):549-54

Assessment of oestrogenic potency of chemicals used as growth promoter by in-vitro methods.
Three in-vitro bioassays were used to compare the oestrogenic potency of chemicals used as growth promoter in beef cattle in certain non-European Union countries (17beta-oestradiol, alpha-zearalanol, testosterone, trenbolone, trenbolone acetate, melengestrol acetate) or found as food contaminant such as the mycotoxin zearalenone and some of their metabolites (17alpha-oestradiol, oestrone, 17alpha-epitestosterone, 19-nortestosterone, androstendione, zearalanone, alpha-zearalanol, beta-zearalanol, alpha-zearalenol, beta-zearalenol). The strong oestrogens 17alpha-ethinyl oestradiol and diethylstilboestrol were used as standards. The first bioassay was based on the activation of a reporter gene by oestrogens in recombinant yeast expressing human or rainbow trout oestrogen receptor. In the second bioassay, the vitellogenin gene induction of rainbow trout hepatocyte cultures was used as a biomarker for the exposure to oestrogens. The third bioassay was based on the alkaline phosphatase gene induction by oestrogens in the human endometrial Ishikawa cell line. The assessment of oestrogenic potency of these chemicals clearly demonstrates the strong oestrogenicity of the mycotoxin zearalenone and its metabolites and particularly alpha-zearalenol which was as potent as ethinyl oestradiol and diethylstilboestrol in the human endometrial Ishikawa cell line.

Hum Reprod. 2001 May;16(5):1030-6

Role of the insulin-like growth factor family in cancer development and progression.
The insulin-like growth factors (IGFs) are mitogens that play a pivotal role in regulating cell proliferation, differentiation, and apoptosis. The effects of IGFs are mediated through the IGF-I receptor, which is also involved in cell transformation induced by tumor virus proteins and oncogene products. Six IGF-binding proteins (IGFBPs) can inhibit or enhance the actions of IGFs. These opposing effects are determined by the structures of the binding proteins. The effects of IGFBPs on IGFs are regulated in part by IGFBP proteases. Laboratory studies have shown that IGFs exert strong mitogenic and antiapoptotic actions on various cancer cells. IGFs also act synergistically with other mitogenic growth factors and steroids and antagonize the effect of antiproliferative molecules on cancer growth. The role of IGFs in cancer is supported by epidemiologic studies, which have found that high levels of circulating IGF-I and low levels of IGFBP-3 are associated with increased risk of several common cancers, including those of the prostate, breast, colorectum, and lung. Evidence further suggests that certain lifestyles, such as one involving a high-energy diet, may increase IGF-I levels, a finding that is supported by animal experiments indicating that IGFs may abolish the inhibitory effect of energy restriction on cancer growth. Further investigation of the role of IGFs in linking high energy intake, increased cell proliferation, suppression of apoptosis, and increased cancer risk may provide new insights into the etiology of cancer and lead to new strategies for cancer prevention.

J Natl Cancer Inst. 2000 Sep 20;92(18):1472-89

Plasma levels of insulin-like growth factor-1 and binding protein-3, and their association with bladder cancer risk.
PURPOSE: Because insulin-like growth factors (IGFs) and their binding proteins have been implicated in the development of prostate, breast, colon and lung cancer, we examined the role of IGF-1 and IGF binding protein-3 levels in bladder cancer risk. MATERIALS AND METHODS: We used an enzyme-linked immunosorbent assay to compare plasma levels of IGF-1 and IGF binding protein-3 in 154 patients with bladder cancer and 154 controls from an ongoing case-control study. RESULTS: Mean IGF-1 was significantly higher in cases than in controls (175.8 versus 153.2 ng./ml., p <0.01). Mean IGF binding protein-3 was significantly lower in cases than in controls (2,632.9 versus 3,056.6 ng./ml., p <0.01). The highest quartile plasma levels of IGF-1 were associated with an increased risk of bladder cancer (OR 3.10, 95% CI 1.43 to 6.70) and the highest quartile plasma levels of IGF binding protein-3 were associated with a reduced risk of bladder cancer (OR 0.38, 95% CI 0.19 to 0.78). The effects were more striking when IGF-1 and IGF binding protein-3 levels were analyzed together. In addition, a higher molar ratio of IGF-1-to-IGF binding protein-3 was associated with an increased risk of bladder cancer (OR 4.30, 95% CI 1.99 to 9.28). Dose-response relationships were evident when subjects were categorized into quartiles by the values of IGF-1, IGF binding protein-3 and the molar ratio in controls. CONCLUSIONS: To our knowledge this is the first study to suggest that patients with bladder cancer have higher plasma levels of IGF-1 and lower levels of IGF binding protein-3 than controls. Thus, measuring plasma IGF-1 and IGF binding protein-3 may be useful for assessing bladder cancer risk.

J Urol. 2003 Feb;169(2):714-7

Effect of an accelerated finishing program on performance, carcass characteristics, and circulating insulin-like growth factor I concentration of early-weaned bulls and steers.
Sixty-three Angus x Simmental calves were allotted to a bull or a steer group based on sire, birth date, and birth weight to determine effects of castration status on performance, carcass characteristics, and circulating insulin-like growth factor I (IGF-I) concentrations in early-weaned cattle. At 75 d of age, calves in the steer group were castrated. Calves were not creep-fed prior to weaning. All calves were weaned and weighed at an average age of 115 d and transported by truck to the OARDC feedlot in Wooster, OH. Performance and carcass characteristics were measured in three phases. Phase 1 was from 115 to 200 d of age, phase 2 was from 201 to 277 d of age, and phase 3 was from 278 d of age to slaughter. Before implantation, four bulls and four steers were selected for serial slaughter and carcass evaluation. Steers were implanted with Synovex-C at 130 d of age and with Revalor-S at 200 and 277 d of age. Serum samples were collected from all calves on the day of implantation, 28 and 42 d after implantation, and at slaughter and analyzed for circulating IGF-I concentration. Bulls gained 9.7% faster (1.75 vs 1.60 kg/d; P < 0.01), consumed 25 kg more DM (521 vs 496 kg; P = 0.11), and were 3.3% more efficient (282 vs 273 g/kg, P < 0.10) than steers in phase 1. However, steers gained 10.5% faster (1.62 vs 1.46 kg/d; P < 0.02), consumed similar amounts of DM, and were 6.5% more efficient than bulls (214 vs 201 g/kg; P < 0.06) in phase 2. Overall gains and efficiency were similar between bulls and steers; however, bulls consumed 140 kg more DM (P < 0.05), were 27 kg heavier (P < 0.05), and had to stay in the feedlot 18 more days (P < 0.05) than steers to achieve a similar amount of fat thickness. Implanted steers had greater concentrations of circulating IGF-I than bulls (P < 0.01), and the pattern of IGF-I concentration over time was affected by castration status (castration status x time interaction; P < 0.01). Synovex-C had a lower impact on circulating IGF-I concentration (implant effect, P < 0.01) than either Revalor-S implant. Eighty-five percent of both bulls and steers had marbling scores sufficient to grade low Choice or better. Bulls achieved their target fat thickness later, increased muscle growth, and deposited fat more favorably than steers, possibly due to a gradual increase in IGF-I concentration as the testicles grew rather than the large fluctuations in IGF-I concentration observed in steers following implantation.

J Anim Sci. 2002 Apr;80(4):900-10

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