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Recent evidence suggests that the A allele of the ornithine decarboxylase (ODC) gene is a genetic risk factor for prostate cancer. ODC is a target gene of the highly polymorphic androgen receptor (AR) gene, short alleles of which have been associated in some studies with increased prostate cancer risk. We determined ODC allele frequencies and distribution of AR alleles in American Caucasians, African-Americans, Hispanics, Europeans, and Africans. The frequency of the ODC A allele varied from 0.183 (Hispanics, Europeans) to 0.415 (Africans) with American Caucasian and African-Americans having intermediate values. The mean number of CAG repeats in the AR gene varied from 19.8 (African-Americans) to 25.1 (Hispanics). It is possible that ethnic differences in risk alleles for ODC and AR may account for some of the ethnic variation in prostate cancer risk., (Copyright 2004 Wiley-Liss, Inc.)

Background: Selenium and alpha-tocopherol, the major form of vitamin E in supplements, appear to have a protective effect against prostate cancer. However, little attention has been paid to the possible role of gamma-tocopherol, a major component of vitamin E in the U.S. diet and the second most common tocopherol in human serum. A nested case-control study was conducted to examine the associations of alpha-tocopherol, gamma-tocopherol, and selenium with incident prostate cancer., Methods: In 1989, a total of 10,456 male residents of Washington County, MD, donated blood for a specimen bank. A total of 117 of 145 men who developed prostate cancer and 233 matched control subjects had toenail and plasma samples available for assays of selenium, alpha-tocopherol, and gamma-tocopherol. The association between the micronutrient concentrations and the development of prostate cancer was assessed by conditional logistic regression analysis. All statistical tests were two-sided., Results: The risk of prostate cancer declined, but not linearly, with increasing concentrations of alpha-tocopherol (odds ratio (highest versus lowest fifth) = 0.65; 95% confidence interval = 0.32--1.32; P(trend) =.28). For gamma-tocopherol, men in the highest fifth of the distribution had a fivefold reduction in the risk of developing prostate cancer than men in the lowest fifth (P:(trend) =.002). The association between selenium and prostate cancer risk was in the protective direction with individuals in the top four fifths of the distribution having a reduced risk of prostate cancer compared with individuals in the bottom fifth (P(trend) =.27). Statistically significant protective associations for high levels of selenium and alpha-tocopherol were observed only when gamma-tocopherol concentrations were high., Conclusions: The use of combined alpha- and gamma- tocopherol supplements should be considered in upcoming prostate cancer prevention trials, given the observed interaction between alpha-tocopherol, gamma-tocopherol, and selenium.

We used a nested case-control design on data from men in four prospective studies (from the UK, Maryland in the USA, and two from Finland) with available stored serum samples to determine whether there was an advantage in measuring both free prostate-specific antigen (PSA) and total PSA as a potential screening test for prostate cancer. Of these men, 247 were verified through national vital statistics offices as having died of prostate cancer, or having developed the disease, and 953 men who did not develop prostate cancer (controls) were selected, matched to cases for age, study centre and sample storage duration. Fixing the false-positive rate at 1%, the prostate cancer detection rate (sensitivity) over the 3 years following serum collection (based on 14 cancers) increased from an estimated 95% using total PSA to 97% using free and bound PSA (that is, bound to alpha-antichymotrypsin which together with the free form is total PSA). Over a 6-year period (based on 41 cancers) a similar difference occurred (52% and 56% detection rates respectively). We conclude that there is no material advantage in adding free to total PSA in prostate cancer screening trials.

Objective: To evaluate measurement of serum prostate specific antigen as a potential screening test for future clinical prostate cancer among healthy men., Design: Nested case-control study with stored serum samples collected from 49,261 men with follow up using national death and cancer registration systems., Subjects: 265 asymptomatic men who subsequently developed clinical prostate cancer and 1055 controls matched for age, study centre, and duration of storage of samples., Main Outcome Measures: Distribution of concentrations of the antigen in men who developed prostate cancer and in controls., Results: Prostate specific antigen concentrations were significantly higher in men who subsequently developed prostate cancer than in controls. In the first three years after blood collection the median concentration was 23 times greater in cases than in controls of the same age at the same centre (that is, 23 multiples of the median). A smaller difference persisted thereafter; 4.0 multiples of the median 3-6 years after blood collection, 3.6 6-10 years, and 1.8 after 10 years. In the first three years the proportion of men who developed prostate cancer and had raised levels of the antigen (> or = 12 multiples of the median) (detection rate or sensitivity) was 81% (95% confidence interval 54% to 96%). The proportion of men who did not develop prostate cancer but had levels this high (false positive rate) was only 0.5%., Conclusion: Prostate specific antigen measurement is a highly discriminatory screening test for prostate cancer among healthy men. In the general population, 60-74 year old men who had > or = 12 times the normal median level would have about a 50% chance of developing clinical prostate cancer in the next three years. Measurement of this antigen is a good enough screening test to justify a randomised controlled trial to determine any reduction in mortality from prostate cancer.

An hypothesis has been forwarded linking prostate cancer to low serum levels of vitamin D metabolites. We sought to test this hypothesis using sera obtained in a large, prospective cohort study. A serum bank in Washington County, Maryland (United States) has stored sera obtained from 20,305 county residents during a blood collection campaign undertaken in August through November 1974. We studied sera obtained from 61 residents who were diagnosed with prostate cancer during the period 1980 through 1992. Each prostate cancer case was matched to two controls on age (+/- 1 yr) and race. Controls had donated blood in the same blood-collection campaign and had not been diagnosed with prostate cancer through 1992. Serum levels of vitamin D metabolites did not differ significantly between cases and controls. Mean 25-hydroxyvitamin D (25-D) levels were 34.3 ng/ml and 33.2 ng/ml, and mean 1,25-dihydroxyvitamin D (1,25-D) levels were 41.0 pg/ml and 40.1 pg/ml, in cases and controls, respectively. No statistically significant trends or differences between cases and controls were found in an analysis by quintile of serum level. We also did not observe the association of vitamin D metabolites with prostate cancer to be strongest among older men with more severe disease, as previously has been reported. In summary, although our study's power was limited, our findings provide little support for the hypothesis that vitamin D metabolite levels are associated strongly with subsequent risk for prostate cancer.

Prostate-specific antigen levels are increased in men with prostatic disease, including prostate cancer, and have been used clinically to monitor the response of prostate cancer to therapy. More recently, prostate-specific antigen levels, usually in combination with digital rectal examination or transrectal prostatic ultrasonography, have been suggested to be useful for the detection of prostate cancer. To evaluate the association between a single serum prostate-specific antigen level and the subsequent development of prostate cancer, we measured serum levels in 35 men who donated blood to a community-based serum bank in 1974 and who subsequently developed prostate cancer and in 35 matched controls from the same group of volunteers. Levels of prostate-specific antigen were significantly higher in men who went on to develop prostate cancer, up to 6 years prior to the time of diagnosis in the cases. The level of prostate-specific antigen decreased with increasing time to diagnosis. The mean level for prostate cancer cases diagnosed within the first 3 years of follow-up was 16.2 micrograms/liter compared to 2.4 micrograms/liter for controls (P = 0.002). The mean level for cancer cases diagnosed in years 4 through 6 following blood sampling was 9.6 micrograms/liter compared to 1.3 micrograms/liter for controls (P = 0.0002). The sensitivity and specificity of a prostate-specific antigen level > or = 4 micrograms/liter up to 3 years prior to the time of clinical diagnosis were both 75% and up to 6 years were 67% and 85%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)