Is prostate cancer stage migration continuing for black men in the PSA era?

BACKGROUND: In the United States, disease-specific mortality from prostate cancer (PC) is highest among black men. While the introduction of widespread PSA testing has been associated with a downward stage migration, whether this trend continues in the late PSA era and for black men is unknown. The objective of our study was to evaluate current PC stage migration patterns in the United States by race. METHODS: The Surveillance, Epidemiology and End Results (SEER) registry was queried to obtain all cases of PC reported between 2000 and 2013. Year of diagnosis was categorized into 2000-2003, 2004-2007, 2008-2010 and 2011-2013. Predictors of distant stage PC at diagnosis were determined using logistic regression adjusted for year of diagnosis, age at diagnosis, SEER region and race. RESULTS: A total of 791 184 PC cases were identified. The cohort comprised 78.9% (n=594 920) white and 14.1% (n=106 133) black men. The stage at diagnosis was 83.3% localized, 12.0% regional and 4.7% distant. Age-adjusted incidence demonstrated a steady decline for black men in all time groups while white men had a stable incidence of distant disease between 2000 and 2013. In univariate analysis, black men in the 2004-2007 (OR 0.86 (0.81-0.93)) and 2008-2010 cohorts (OR 0.85 (0.79-0.91)) were less likely to be diagnosed with metastatic PC as compared with the 2000-2003 baseline cohort. In multivariate analysis, the 2004-2007 black cohort was less likely to be diagnosed with distant PC (OR 0.90 (0.84-0.97)). This trend was not observed in white men who in multivariate analysis had an increased risk of distant PC in the 2004-2007 (OR 1.08 (1.04-1.11)), 2008-2010 (OR 1.22 (1.18-1.27)) and 2011-2013 (OR 1.65 (1.59-1.71)) groups. CONCLUSIONS: PC downward stage migration continues in black men but not in white men. Discontinuation of PSA-based screening for PC could disproportionately affect black men.

Assessing the effect of fatty acids on prostate carcinogenesis in humans: does self-reported dietary intake rank prostatic exposure correctly?

BACKGROUND: Dietary fatty acids may influence prostate carcinogenesis. Although the standard for assessing dietary effects in humans is the semiquantitative food-frequency questionnaire, the extent to which self-reported intake correctly ranks prostatic exposure is unknown. OBJECTIVE: The objective was to examine the correlation between reported intakes of different fatty acids and their concentrations in prostate tissue. DESIGN: This was a cross-sectional study of 52 men undergoing surgical resection of the prostate gland. Usual dietary intake of saturated, total unsaturated, oleic, and linoleic fatty acids over the previous year was estimated with use of a 122-item version of the Health Habits and History Questionnaire. Concentrations in prostate tissue were measured directly by use of gas chromatography in healthy tissue collected at the time of surgery and were expressed as a percentage of total fatty acids. Correlations with 4 measures of dietary intake [g/d, g/d adjusted for total daily energy intake, % of total fat (as g/d), and % of total energy] were evaluated by Spearman's rank-order correlation coefficients. RESULTS: Linoleic acid concentrations in prostate tissue were significantly correlated with dietary intake expressed as g/d adjusted for total energy [r = 0.29 (95% CI: 0.03, 0.49), P = 0.04], % of total fat [r = 0.36 (0.14, 0.550), P = 0.008], and % of total energy [r = 0.28 (0.04, 0.49), P = 0.042], but not as g/d. Although mean concentrations of saturated, total unsaturated, and oleic fatty acids in prostate tissue resembled mean intakes for the group, prostatic concentrations did not correlate with individual intakes. CONCLUSION: Self-reported intake of fatty acids is a satisfactory marker of prostatic exposure at the group level, but, with the exception of linoleic acid, does not correctly rank individuals with respect to intensity of exposure.

Height and risk of fatal prostate cancer: findings from the National Health Interview Survey (1986 to 1994).

PURPOSE: Height is determined by genetic and nutritional factors mediated through the endocrine system early in life and, thus, may be related to subsequent risk of fatal prostate cancer. This hypothesis was examined in a large representative U.S. national sample. METHODS: Data from the National Health Interview Survey (NHIS) were analyzed to determine whether height was prospectively related to the risk of fatal prostate cancer in 110,042 men age > or = 50 years old interviewed between 1986 and 1994. Height was self-reported and vital status and causes of death ascertained using the National Death Index. Endpoints were deaths that listed prostate cancer as the underlying cause and deaths with any mention of prostate cancer. Relative risks (RR) and their 95% confidence intervals (CI) were calculated using Cox proportional hazards models adjusted for age, race, weight, and education. RESULTS: Six hundred and thirty-three deaths listing of prostate cancer as the underlying cause and 910 deaths with any mention of prostate cancer were identified. Height was associated neither with risk of death with prostate cancer listed as the underlying cause nor with risk of death with any mention of prostate cancer (multivariate p for trend = 0.1318 and 0.0698, respectively). Risks were marginally greater among the tallest men compared to the shortest (< or = 171.4 vs. > or = 182.9 cm), but not significantly (RR = 1.21, 95% CI = 0.92 to 1.57, and RR = 1.24, 95% CI = 0.98 to 1.58 for 'underlying cause' and 'any mention', respectively). CONCLUSIONS: Height alone was not related to risk of fatal prostate cancer in this population.

Prostatic levels of fatty acids and the histopathology of localized prostate cancer.

PURPOSE: The consumption of various fatty acids has been associated with advanced stage and fatal prostate cancer. While numerous mechanisms have been postulated, to our knowledge there physiological data linking exposure and prognosis in humans are lacking. We examined prostatic levels of individual fatty acids in relation to the prevalence of histopathological characteristics associated with invasiveness and the risk of progression in 49 men undergoing radical prostatectomy for localized prostate cancer. MATERIALS AND METHODS: Fatty acids were measured using capillary gas chromatography in fresh nonmalignant prostate tissue collected at surgery. Markers of invasiveness and increased risk of progression (Gleason sum 7 or greater, perineural invasion, anatomical or surgical margin involvement, extracapsular extension, seminal vesical involvement and stage T3 tumor) were evaluated separately. Each marker was dichotomized into a yes (case) and no (control) level with patients grouped accordingly. Mean concentrations were compared using the Wilcoxon rank sum test. RESULTS: The percent of total prostatic polyunsaturated fat and polyunsaturated-to-saturated fat ratios were significantly lower in the presence of perineural invasion, seminal vesical involvement and stage T3 tumor (p = 0.02 to 0.049). alpha-Linolenic acid was significantly lower when tumor extended to an anatomical or surgical margin (p = 0.008). The omega-3 and omega-3-to-omega-6 fatty acid ratios were 1.5 to 3.3-fold lower in cases than in controls, reaching borderline significance in nearly all comparisons (p = 0.052 to 0.097). Saturated and monounsaturated fatty acids were not associated with the traits examined. CONCLUSIONS: These data suggest that polyunsaturated fatty acids and perhaps essential fatty acids in particular help to regulate prostate carcinogenesis in humans.

Prostatic levels of tocopherols, carotenoids, and retinol in relation to plasma levels and self-reported usual dietary intake.

This study evaluated how prostatic levels of antioxidants relate to plasma levels and self-reported usual dietary intake. Definition of these relations may aid in interpreting studies of antioxidant exposure and prostate cancer risk. Between July 1996 and April 1997, plasma and prostatic tissue levels of tocopherols, carotenoids, and retinol were measured in 47 men undergoing radical prostatectomy or transurethral prostatectomy at Loyola University Medical Center, Maywood, Illinois, and an affiliate hospital. Dietary intake was measured by using a 122-item version of the Block Health Habits and History Questionnaire, and correlations were assessed with Pearson's coefficients. Prostatic levels of tocopherols and carotenoids (but not retinol) were significantly correlated with plasma levels (r= 0.31-0.56, p < 0.05-0.0001); the strongest correlations were associated with lycopene, beta-carotene, and gamma-tocopherol (0.56, 0.54, and 0.52, respectively; p < 0.0001). Relative concentrations of tocopherols and carotenoids in prostate tissue were proportionate to those in plasma. No correlation between prostatic levels and reported dietary intake was observed (r = -0.09 to 0.16, p < not significant). Adjustment for energy intake, body mass index, and serum lipids did not impact these relations. These results suggest that plasma levels of tocopherols and carotenoids better reflect prostatic exposure than self-reported usual dietary intake.

Limitations in the use of race in the study of disease causation.

Tremendous variation exists in the rates of many chronic diseases across racial groups. However, serious technical and conceptual limitations hamper the ability of racial comparisons to illuminate the causative pathways. First, race is confounded by social class, which is complex, and like other confounders of race, may not be measured with equal validity across racial groups. Second, statistical "adjustments" for race effects can be misleading since residual confounding may be misconstrued as a genetic effect. Third, the biologic concept of race tempts us to ignore the context dependency of genetic expression. When trying to detect genetic effects, both the environmental and genetic contributions must be measured and potential gene-environment interactions accounted for. Unfortunately, this process is beyond our current technical capabilities. To move forward on the problem of prostate cancer and other diseases distinguished by marked ethnic differentials, investigators need a more comprehensive understanding of the factors that mediate the apparent effect of race combined with valid measures of those factors, as well as novel strategies that can help overcome the technical and interpretive limitations of statistical adjustment. Finally, the "grand" theories of race-based genetic susceptibility must be replaced with rigorous criteria to determine when a trait can be ascribed to some genetic origin.

Race and the histologic grade of prostate cancer.

We collected data on the histologic grade, stage, and age at diagnosis of 4,114 cases of prostate cancer (1,380 blacks, and 2,734 whites) in the Chicago area. The relationship between histologic grade (high = poorly or undifferentiated vs. low = well or moderately differentiated) and race (black vs. white) was examined using logistic regression. After adjusting for stage (localized, regional, and distant), the odds of high histologic grade prostate cancer in blacks compared to whites equaled 1.7 (95% CI [1.4, 2.0], P < 0.0001). These data suggest that blacks have a significantly higher burden of high histologic grade prostate cancer than whites, even after adjustment for stage at presentation. This higher burden may explain, in part, their higher mortality rate from prostate cancer given the U.S. black vs. white difference in prostate cancer mortality of a similar magnitude.