The effects of selenium and the GPx-1 selenoprotein on the phosphorylation of H2AX.

BACKGROUND: Significant data supports the health benefits of selenium although supplementation trials have yielded mixed results. GPx-1, whose levels are responsive to selenium availability, is implicated in cancer etiology by human genetic data. Selenium's ability to alter the phosphorylation of the H2AX, a histone protein that functions in the reduction of DNA damage by recruiting repair proteins to the damage site, following exposure to ionizing radiation and bleomycin was investigated. METHODS: Human cell lines that were either exposed to selenium or were transfected with a GPx-1 expression construct were exposed to ionizing radiation or bleomycin. Phosphorylation of histone H2AX was quantified by flow cytometry and survival by the MTT assay. Phosphorylation of the Chk1 and Chk2 checkpoint proteins was quantified by western blotting. RESULTS: In colon-derived cells, selenium increases GPx-1 and attenuated H2AX phosphorylation following genotoxic exposures while the viability of these cells was unaffected. MCF-7 cells and transfectants that express high GPx-1 levels were exposed to ionizing radiation and bleomycin, and H2AX phosphorylation and cell viability were assessed. GPx-1 increased H2AX phosphorylation and viability following the induction of DNA damage while enhancing the levels of activated Chk1 and Chk2. CONCLUSIONS: Exposure of mammalian cells to selenium can alter the DNA damage response and do so by mechanisms that are dependent and independent of its effect on GPx-1. GENERAL SIGNIFICANCE: Selenium and GPx-1 may stimulate the repair of genotoxic DNA damage and this may account for some of the benefits attributed to selenium intake and elevated GPx-1 activity.

Changes in BMI modulate age-associated changes in sex hormone binding globulin and total testosterone, but not bioavailable testosterone in young adult men: the CARDIA Male Hormone Study.

OBJECTIVES: To compare age-associated 8-year changes in total testosterone, calculated bioavailable testosterone and sex hormone binding globulin (SHBG) across five groups of men stratified according to change in body mass index (BMI) (i.e., BMI stable (+/-0.69 kg/m(2)), decreased (-0.7 kg/m(2)), increased minimally (0.7-1.74 kg/m(2)), increased moderately (1.75-3.19 kg/m(2)) and increased most (> or =3.20 kg/m(2))). DESIGN: Eight-year longitudinal cohort study. SUBJECTS: Four hundred and seventy-four black and 695 white men, aged 24-31 years at the time of the first hormone measurement. MEASUREMENTS: Aging-related changes in serum SHBG, total testosterone and bioavailable testosterone. RESULTS: SHBG significantly increased with age for men whose BMI decreased, and there were progressively smaller increases for men whose BMI was stable, or whose BMI increased minimally or moderately (range 1.1-0.3 nM per year, P< or =0.03, respectively). There was no age relationship with SHBG among men whose BMI increased most. Total testosterone did not change with age for men whose BMI decreased, was stable or increased minimally, but for men whose BMI increased moderately and most there was a graded decrease in total testosterone with age (beta=-0.2 and -0.4 nM per year, respectively, P< or =0.005). However, bioavailable testosterone decreased with age to a similar extent across all groups. CONCLUSIONS: These results suggest that changes in BMI during young adulthood modulate age-related changes in SHBG and total testosterone, but not bioavailable testosterone.

Immunohistochemical assays in prostatic biopsies processed in Bouin's fixative.

AIMS: To investigate the problems involved in undertaking immunohistochemistry (IHC) and nuclear morphometry using Bouin's fixed prostate biopsies. METHODS: Archival Bouin's fixed and formalin fixed, paraffin wax embedded prostatic biopsies were immunostained for three nuclear biomarkers (minichromosome maintenance protein 2 (MCM-2), p27, and Ki-67), one membrane localised biomarker (C-erb-B2), CD34, and alpha methylacyl-CoA racemase (AMACR). The quality of IHC staining was compared between tissues prepared separately in both fixatives. Feulgen staining was also performed on Bouin's fixed tissues to check its suitability for nuclear morphometry. RESULTS: MCM-2 staining was completely negative in Bouin's fixed tissues, whereas p27 showed more background and excess cytoplasmic staining in Bouin's fixed versus formalin fixed tissues. C-erb-B2 showed non-specific, strong luminal cell staining in the Bouin's fixed tissue. Feulgen staining was also very weak in Bouin's fixed tissue. However, Ki-67, AMACR, and CD34 worked equally well in Bouin's and formalin fixed tissues. CONCLUSIONS: Bouin's fixed tissues may be unsuitable when subsequent IHC and morphometry are contemplated. An awareness of which antibodies are suitable for use in Bouin's fixed biopsies is essential.

Postload plasma glucose concentration and 27-year prostate cancer mortality (United States).

OBJECTIVE: Findings from epidemiologic studies on the association between diabetes and prostate cancer risk are inconsistent. However, data from at least three studies suggest that the direction and strength of this association differs according to duration of diabetes. To determine the potential effects of early-stage abnormal glucose metabolism on risk, we assessed the relationship of postload glycemia in the absence of self-reported diabetes with risk of prostate cancer mortality. METHODS: Data from the Chicago Heart Association Detection Project in Industry were used to examine this relationship. Between 1967 and 1973 some employees of 84 Chicago area organizations underwent a health screening examination. Blood was drawn for measurement of plasma glucose concentration approximately 1 h after a 50-g oral glucose load among 20,433 men. After a mean length of follow-up of 27 years, 176 men died of prostate cancer. Cox regression was used to compute adjusted relative risks (RRs) and 95% confidence intervals (CIs). RESULTS: After controlling for age, body mass index, heart rate, education, and race, the RRs of prostate cancer mortality for postload plasma glucose levels of 6.7-8.8, 8.9-11, and > or = 11.1 mmol/L compared to < or = 6.6 mmol/L were 1.64, 1.37, and 1.64. respectively (p for trend=0.19). The RR (95% CI) associated with a 2.2 mmol/L (1 standard deviation) higher glucose concentration was 1.1 (0.95-1.2). CONCLUSIONS: These results provide weak evidence of an association between hyperglycemia and prostate cancer mortality.

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 1012 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.

Saliva as a medium for investigating intra- and interindividual differences in sex hormone levels in premenopausal women.

Repeated measurement of ovarian steroids in saliva could provide an advantage in studies estimating long-term sex steroid exposure in premenopausal women, by reducing the measurement error associated with collection of serum or urine samples. We previously reported on characteristics of ultrasensitive RIAs adapted for extraction-free measurement of estradiol (E2) and progesterone (PG) in saliva. The purpose of the present study was to evaluate the consistency of E2 and PG levels in saliva in the same women across menstrual cycles, and to compare this with the variation observed between women. We also evaluated the effect of altering the number of consecutive daily samples considered and the method for locating a particular cycle day in relation to ovulation (day 0). Study participants included 12 healthy women who provided daily saliva samples for two consecutive, ovulatory menstrual cycles. A single midluteal serum sample was collected 7-8 days after detection of a luteinizing hormone (LH) peak in urine. We plotted individual cycle profiles and computed intraclass correlation coefficients (ICC) for various definitions of peak and cumulative daily hormone level. For peak PG, determined as the maximal running 3-day mean, ICC was 0.68. For cumulative PG, based on 8 consecutive cycle days (+2 to +9), ICCs were 0.72-0.76 when reverse dating LH peak or rise in salivary PG determined day 0. For E2, ICCs ranged from 0.74 to 0.79 by various dating methods for the 5 preovulatory days (-4-0), and from 0.85 to 0.92 for the 15 days about the center of the cycle (-6 to +8). With exclusion of just the first 5 days of the cycle, the ICC for E2 was 0.91. For both E2 and PG, selection of 5 or 7 days for the estimation of the midluteal mean level provided separation of within and between subject variance that was comparable with a LH-timed serum sample. These results indicate that daily saliva samples can be combined to clarify the interindividual differences in E2 and PG levels in premenopausal women, and that these interindividual differences may be greater than previously imagined.

Abnormal glucose metabolism and pancreatic cancer mortality.

CONTEXT: Previous studies reported an increased risk of pancreatic cancer among persons with diabetes. Few data exist, however, on the association of postload plasma glucose concentration with pancreatic cancer, which could provide insight into the role of abnormal glucose metabolism in the etiology of pancreatic cancer. OBJECTIVE: To determine the independent association between postload plasma glucose concentration and risk of pancreatic cancer mortality among persons without self-reported diabetes. DESIGN: Prospective cohort study. SETTING AND PARTICIPANTS: Employees of 84 Chicago-area organizations, with an average age of 40 years at baseline, were screened from 1963 to 1973 and followed up for an average of 25 years. A total of 96 men and 43 women died of pancreatic cancer among 20,475 men and 15,183 women, respectively. MAIN OUTCOME MEASURES: Relationship of pancreatic cancer mortality with postload plasma glucose levels. RESULTS: Compared with a postload plasma glucose level of 6.6 mmol/L (119 mg/dL) or less and after adjusting for age, race, cigarette smoking, and body mass index, the relative risks (95% confidence intervals) of pancreatic cancer mortality were 1.65 (1.05-2.60) for postload plasma glucose levels between 6.7 (120) and 8.8 (159) mmol/L (mg/dL); 1.60 (0.95-2.70) for levels between 8.9 (160) and 11.0 (199); and 2.15 (1.22-3.80) for levels of 11.1 (200) or more; P for trend=.01. An association appeared to be stronger for men than women. Estimates were only slightly lower after excluding 11 men and 2 women who died of pancreatic cancer during the first 5 years of follow-up. In men only, higher body mass index and serum uric acid concentration also were independently associated with an elevated risk of pancreatic cancer mortality. CONCLUSION: These results suggest that factors associated with abnormal glucose metabolism may play an important role in the etiology of pancreatic cancer. JAMA. 2000;283:2552-2558

Factors associated with axillary lymph node metastasis from breast carcinoma: descriptive and predictive analyses.

BACKGROUND: Although axillary lymph node metastasis is one of the most important prognostic determinants of breast carcinoma prognoses, the reasons why tumors vary in their capability to produce for axillary metastases remain unclear. METHODS: The authors used data from the nationwide Patient Care Evaluation (PCE) survey of the American College of Surgeons to evaluate the correlations between patient/tumor characteristics and lymph node status, and to explore the use of these factors, which are all known prior to axillary dissection, in predicting lymph node status. The PCE data set contained 18,025 breast carcinoma cases diagnosed in 1990 after exclusion of women older than 79 years or with fewer than 6 lymph nodes examined. RESULTS: In a multivariate logistic regression model, larger tumor size, young age, African American or Hispanic race, outer half tumor location, poor or moderate differentiation, aneuploidy, and infiltrating ductal histology were independently associated with a higher likelihood of one or more positive lymph nodes. Contrary to expectation, cases negative for estrogen receptor (ER) and progesterone receptor (PR) had a lower risk of positive lymph nodes when adjusted for other factors (odds ratio = 0.82; 95% confidence interval: 0.74-0.91) compared with cases positive for both receptors. This model accurately predicted lymph node status in 2 validation data sets (a 50% random sample of 1990 PCE data and 1992 data from the National Cancer Data Base), but was less accurate in a third, older data set (1983 PCE data). However, the percentage of cases (1990 validation set) with predicted probabilities less than 0.05 or greater than 0.95 were only 4.6% and <0.1%, respectively. CONCLUSIONS: The authors concluded that 1) most variation in axillary lymph node metastatic status can be explained by routinely available data, 2) ER and PR status may be involved in the mechanism of this behavior, and 3) the difficulty of using prediction models to avert axillary dissection should not be underestimated.

Growth factors in expressed prostatic fluid from men with prostate cancer, BPH, and clinically normal prostates.

BACKGROUND: Although growth factors such as epidermal growth factor (EGF), transforming growth factor (TGF)-alpha, and TGF-beta are important regulators of prostate cell growth in vitro and in animal models, evidence to support their role in human prostate cancer development remains sparse. We previously showed that men without prostate cancer have concentrations of EGF and TGF-alpha in expressed prostatic fluid (EPF) that are individually distinct and stable over time. This study addressed whether growth factor levels in EPF are associated with the presence or progression of prostate cancer. METHODS: We measured levels of immunoreactive EGF, TGF-alpha, and TGF-beta1 in stored EPF samples from three age-matched groups: 19 men with untreated, histologically diagnosed prostate cancer (CaP), 38 with benign prostate hyperplasia (BPH), and 19 with normal prostate glands (NPD). RESULTS: Median TGF-alpha was lower in the BPH group (0.45 ng/ml) than in either CaP (0.63 ng/ml) or NPD (0.58 ng/ml) groups (P = 0.03 and 0.12, respectively). For EGF, the median was lowest in the CaP group and highest in the NPD group (92.5 ng/ml vs. 175.5 ng/ml, P = 0.006). For TGF-beta1, the median level in CaP was 2.7 times higher than the median level among all controls (6.65 ng/ml vs. 2.46 ng/ml, P = 0.002). Growth factor levels were not associated with tumor stage or Gleason score. However, the single case with distant metastases had TGF-beta1 levels 23-fold higher than the CaP median. CONCLUSIONS: The results suggest that at the time of CaP diagnosis, EGF levels in EPF are significantly lower, and TGF-beta1 levels significantly higher, than normal. Marked overexpression of TGF-beta1 in advanced CaP might be reflected in extremely high EPF levels.

Salivary estradiol and progesterone levels in conception and nonconception cycles in women: evaluation of a new assay for salivary estradiol.

OBJECTIVE: To determine the usefulness of salivary E2 and progesterone for noninvasive assessment of ovarian function. DESIGN: Prospective study of salivary hormone levels in women planning a pregnancy. SETTING: Department of Obstetrics and Gynecology at Northwestern University Medical School in Chicago, Illinois. PATIENT(S): Fourteen women aged 23-39 years with regular menstrual cycles who were planning a pregnancy. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Salivary estradiol and progesterone concentrations. RESULT(S): The sensitivity of the E2 assay is 2.0 pmol/L; the interassay coefficient of variation was 5.2% (mean value 17 pmol/L). Recovery of E2 added to saliva was 106%. The correlation with simultaneous serum samples was 0.71. Menstrual cycle patterns contained a preovulatory depression and a midcycle surge. By comparison with nonconception cycles, the luteal phases of conception cycles had significantly elevated salivary E2 within the first 5 days after ovulation. Salivary progesterone was significantly elevated but not until 10 days after ovulation. CONCLUSION(S): Salivary measurements of E2 and progesterone can be used as noninvasive methods for assessment of ovarian function. Salivary specimens can be collected at home and brought to the laboratory for analysis, obviating the need for frequent phlebotomy. The sensitivity and precision of the salivary E2 assay make it comparable with assays of serum E2 for assessing changes in hormone levels.

CAG repeat within the androgen receptor gene and incidence of surgery for benign prostatic hyperplasia in U.S. physicians.

BACKGROUND: CAG repeat length in exon 1 of the androgen receptor (AR) gene correlates inversely with transcriptional transactivation activity of the AR. Men with shorter AR CAG repeat lengths are at higher risk of prostate cancer. Because benign prostatic hyperplasia (BPH) is an androgen-dependent condition, we examined the hypothesis that a shorter AR gene CAG repeat length increases the risk of developing of BPH. METHODS: Among 14,916 men of the Physicians' Health Study who had provided a blood sample in 1982, we measured AR gene CAG repeat lengths for 310 men who had surgery for BPH up to 7.5 years of follow-up and 1,041 controls. RESULTS: Risk of surgery for BPH increased linearly with decreasing AR CAG repeat length (P (trend) = 0.03). Relative to men with a CAG repeat length > or = 25, men with a repeat length < or = 19 had an odds ratio of BPH surgery of 1.76 (95% confidence interval, 1.16-2.65). CONCLUSIONS: Variability in the AR gene CAG repeat influences the development of symptomatic BPH.

Lower prostate cancer risk in men with elevated plasma lycopene levels: results of a prospective analysis.

Dietary consumption of the carotenoid lycopene (mostly from tomato products) has been associated with a lower risk of prostate cancer. Evidence relating other carotenoids, tocopherols, and retinol to prostate cancer risk has been equivocal. This prospective study was designed to examine the relationship between plasma concentrations of several major antioxidants and risk of prostate cancer. We conducted a nested case-control study using plasma samples obtained in 1982 from healthy men enrolled in the Physicians' Health Study, a randomized, placebo-controlled trial of aspirin and beta-carotene. Subjects included 578 men who developed prostate cancer within 13 years of follow-up and 1294 age- and smoking status-matched controls. We quantified the five major plasma carotenoid peaks (alpha- and beta-carotene, beta-cryptoxanthin, lutein, and lycopene) plus alpha- and gamma-tocopherol and retinol using high-performance liquid chromatography. Results for plasma beta-carotene are reported separately. Odds ratios (ORs), 95% confidence intervals (Cls), and Ps for trend were calculated for each quintile of plasma antioxidant using logistic regression models that allowed for adjustment of potential confounders and estimation of effect modification by assignment to either active beta-carotene or placebo in the trial. Lycopene was the only antioxidant found at significantly lower mean levels in cases than in matched controls (P = 0.04 for all cases). The ORs for all prostate cancers declined slightly with increasing quintile of plasma lycopene (5th quintile OR = 0.75, 95% CI = 0.54-1.06; P, trend = 0.12); there was a stronger inverse association for aggressive prostate cancers (5th quintile OR = 0.56, 95% CI = 0.34-0.91; P, trend = 0.05). In the placebo group, plasma lycopene was very strongly related to lower prostate cancer risk (5th quintile OR = 0.40; P, trend = 0.006 for aggressive cancer), whereas there was no evidence for a trend among those assigned to beta-carotene supplements. However, in the beta-carotene group, prostate cancer risk was reduced in each lycopene quintile relative to men with low lycopene and placebo. The only other notable association was a reduced risk of aggressive cancer with higher alpha-tocopherol levels that was not statistically significant. None of the associations for lycopene were confounded by age, smoking, body mass index, exercise, alcohol, multivitamin use, or plasma total cholesterol level. These results concur with a recent prospective dietary analysis, which identified lycopene as the carotenoid with the clearest inverse relation to the development of prostate cancer. The inverse association was particularly apparent for aggressive cancer and for men not consuming beta-carotene supplements. For men with low lycopene, beta-carotene supplements were associated with risk reductions comparable to those observed with high lycopene. These data provide further evidence that increased consumption of tomato products and other lycopene-containing foods might reduce the occurrence or progression of prostate cancer.

Cancer occurrence in the elderly: agreement between three major data sources.

PURPOSE: To explore agreement on cancer occurrence and site among Medicare Part A, Massachusetts Cancer Registry, and death certificates. METHODS: We linked these data sources with the cohort of the population-based East Boston Senior Health Project, a component of the National Institute on Aging's Established Populations for Epidemiologic Studies of the Elderly. The cohort consists of 905 subjects dying between January 1986 and December 1990. RESULTS: We detected the following agreements on cancer occurrence: hospitalization data and death certificates (kappa = 0.70), hospitalization and cancer registry data (kappa = 0.59), and cancer registry and death certificate data (kappa = 0.50). Measures of agreement changed little when the analyses were stratified by age, sex, calendar year and place of death, autopsy performance, cigarette smoking or alcohol consumption. Site-specific agreements were higher for colorectal and respiratory tract cancer compared to breast and prostate across all three comparisons. CONCLUSIONS: The results should assist epidemiologists to better understand the strengths and limitations of these data sources.

Vitamin D receptor polymorphisms, circulating vitamin D metabolites, and risk of prostate cancer in United States physicians.

Prostatic cells express vitamin D receptor (VDR), which mediates the functions of 1,25-dihydroxyvitamin D. Two recent case-control studies suggested strong inverse associations between two VDR polymorphisms, TaqI and poly(A), and risk of prostate cancer. These two and a third polymorphism, BsmI, are closely linked. In a case-control study nested in the Physicians' Health Study, a randomized double-blind trial of aspirin and beta-carotene among 22,071 United States male physicians, we examined the associations between BsmI and TaqI and prostate cancer risk and whether the associations varied according to age and vitamin D metabolite levels among 372 incident cases and 591 controls. Among controls, the BB genotype was significantly associated with higher 1,25-dihydroxyvitamin D (median = 36.2 pg/ml for the BB versus 33.9 pg/ml for the bb genotype; P = 0.02), suggesting an association of the VDR polymorphisms with VDR function. Overall, we observed no significant associations of these VDR polymorphisms with prostate cancer risk: relative risk (RR) = 0.86 [95% confidence interval (CI) = 0.57-1.29] for the BB genotype and RR = 0.92 (95% CI = 0.69-1.22) for the Bb genotype, compared with the bb genotype (results were similar for the TaqI polymorphism). Stratification by age (< or = 61 and > 61 years) and tumor aggressiveness showed no significant associations. However, in an analysis restricted to men with plasma 25-hydroxyvitamin D below the median, we observed a 57% reduction (RR = 0.43, 95% CI = 0.19-0.98) in risk for those with the BB versus the bb genotype; the risk reduction was particularly marked among older men (RR = 0.18, 95% CI = 0.05-0.68). We did not observe this inverse association among men with 25-hydroxyvitamin D levels above the median, nor did we observe it among younger men.

Plasma insulin-like growth factor-I and prostate cancer risk: a prospective study.

Insulin-like growth factor-I (IGF-I) is a mitogen for prostate epithelial cells. To investigate associations between plasma IGF levels and prostate cancer risk, a nested case-control study within the Physicians' Health Study was conducted on prospectively collected plasma from 152 cases and 152 controls. A strong positive association was observed between IGF-I levels and prostate cancer risk. Men in the highest quartile of IGF-I levels had a relative risk of 4.3 (95 percent confidence interval 1.8 to 10.6) compared with men in the lowest quartile. This association was independent of baseline prostate-specific antigen levels. Identification of plasma IGF-I as a predictor of prostate cancer risk may have implications for risk reduction and treatment.

Epidermal growth factor-related peptides in human prostatic fluid: sources of variability in assay results.

BACKGROUND: Prostatic fluid (PF) provides a unique medium for noninvasive evaluation of critical growth and differentiation signals in the prostatic microenvironment. The purpose of this study was to establish the feasibility of measuring two prostatic mitogens, epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) in PF, and specifically to quantify extraneous variability attributable to the assay itself, sample handling, or biological variation within an individual over time. METHODS: PF was collected by transrectal massage from consecutive patients attending a urology clinic. Pooled PF and individual samples from 25 men with stable benign prostatic hyperplasia (BPH) were analyzed for EGF and TGF-alpha by radioimmunoassay and for total protein. RESULTS: Reproducibility was adequate at dilutions as low as 1:50 (2-microliter pooled sample) and 1:5 (20 microliters) for EGF and TGF-alpha, respectively. Results were not affected by freeze-thaw cycles, time in storage, or protease inhibition in fresh PF. EGF and TGF-alpha were detectable in 100% and 92% of individual men, with respective means of 152 and 0.2 ng/ml. Correlations between two samples obtained from the same man within 12 months were highly significant (EGF r = 0.89, TGF-alpha r = 0.71). Protein concentrations were consistent over time; expression of either peptide per weight of protein rather than per volume did not improve within-man correlation. Between-man variability far exceeded within-man variability for both peptides, and was estimated to account for 84% and 61% of the total variability in EGF and TGF-alpha, respectively. There was no correlation between EGF and TGF-alpha in the same samples. CONCLUSIONS: We conclude that men with BPH secrete consistent and distinct levels of EGF-related peptides in PF, and that these levels can be detected with acceptable sensitivity and precision by radioimmunoassay (RIA). Measurement of TGF-alpha, which has not been reported previously, requires a relatively larger sample.