CaP Risk Research Articles

Professions and Working Conditions Associated With Community-Acquired Pneumonia

IntroductionCommunity-acquired pneumonia (CAP) is not considered a professional disease, and the effect of different occupations and working conditions on susceptibility to CAP is unknown. The aim of this study is to determine whether different jobs and certain working conditions are risk factors for CAP. MethodologyOver a 1-year period, all radiologically confirmed cases of CAP (n=1336) and age- and sex-matched controls (n=1326) were enrolled in a population-based case–control study. A questionnaire on CAP risk factors, including work-related questions, was administered to all participants during an in-person interview. ResultsThe bivariate analysis showed that office work is a protective factor against CAP, while building work, contact with dust and sudden changes of temperature in the workplace were risk factors for CAP. The occupational factor disappeared when the multivariate analysis was adjusted for working conditions. Contact with dust (previous month) and sudden changes of temperature (previous 3 months) were risk factors for CAP, irrespective of the number of years spent working in these conditions, suggesting reversibility. ConclusionSome recent working conditions such as exposure to dust and sudden changes of temperature in the workplace are risk factors for CAP. Both factors are reversible and preventable.

Prostate-specific antigen screening and prostate cancer treatment in renal transplantation candidates: A survey of U.S. transplantation centers

IntroductionRenal transplantation candidates are a highly screened population. There are currently no guidelines or consensus on prostate cancer (CaP) screening in these patients. In light of the recent United States Preventive Services Task Force recommendations against prostate-specific antigen (PSA) screening, we conducted a survey of transplantation surgeons to gain a better understanding of practice patterns among U.S. centers. Materials and methodsA 14-question multiple-choice online survey was e-mailed to 195 U.S. renal transplantation centers. The questionnaire assessed CaP screening and treatment practices. The survey also evaluated characteristics of the respondent’s institution. Descriptive statistics were used for each of the responses, and associations were made with program characterization using logistic or linear regression models. ResultsA total of 90 surgeons responded, representing 65 of 195 programs (33% response rate). Overall, 89% of respondents reported routinely screening for CaP in renal transplantation candidates and 71% had set guidelines for PSA screening. The most common age to start PSA screening was 50 years (51%) and 79% of respondents reported no age limit to stop PSA screening. Definitive treatment of CaP was required before proceeding to transplantation in 45% of respondents. Active surveillance was a viable option in 67% of responders. Most respondents (73%) replied that the waiting time for eligibility after treatment depended on the CaP stage and risk. ConclusionsAlthough most programs have guidelines on PSA screening in renal transplantation candidates, there is still variation nationwide in screening and treatment practices. AS is a viable treatment option in most of the programs. Our results suggest a benefit of a consensus panel to recommend guidelines in this population.

MP73-19 PRIMARY ANDROGEN DEPRIVATION THERAPY INCREASES ALL CAUSE MORTALITY IN POPULATIONS MATCHED BY COMORBIDITY ADJUSTED LIFE EXPECTANCY AND DISEASE RISK

You have accessJournal of UrologyProstate Cancer: Advanced I1 Apr 2015MP73-19 PRIMARY ANDROGEN DEPRIVATION THERAPY INCREASES ALL CAUSE MORTALITY IN POPULATIONS MATCHED BY COMORBIDITY ADJUSTED LIFE EXPECTANCY AND DISEASE RISK Jesse Sammon, Firas Abdollah, Gally Reznor, Daniel Pucheril, Akshay Sood, Dane Klett, Julian Hanske, Christian Meyer, Mani Menon, and Quoc-Dien Trinh Jesse SammonJesse Sammon More articles by this author , Firas AbdollahFiras Abdollah More articles by this author , Gally ReznorGally Reznor More articles by this author , Daniel PucherilDaniel Pucheril More articles by this author , Akshay SoodAkshay Sood More articles by this author , Dane KlettDane Klett More articles by this author , Julian HanskeJulian Hanske More articles by this author , Christian MeyerChristian Meyer More articles by this author , Mani MenonMani Menon More articles by this author , and Quoc-Dien TrinhQuoc-Dien Trinh More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.2695AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Primary androgen deprivation therapy (pADT) is commonly used to treat elderly men diagnosed with localized prostate cancer (CaP), despite being highly controversial and unsupported by any meaningful evidence or expert consensus guidelines. We examine the effect of pADT on mortality in elderly men with prostate cancer. To account for the effect of patient illness on life expectancy (LE) we incorporate calculations of comorbidity-adjusted LE (CaLE). METHODS We examine men residing in SEER registry areas, diagnosed with localized or locally advanced CaP between 1992-2009 and forgoing definitive therapy. Propensity score (PS) weighted Cox proportional hazards models were used to estimate the effect of pADT use on overall survival. Analysis was performed on the entire cohort and across comorbidity adjusted life expectancy (<5, 5-10 & >10 yr) and CaP risk sub-groups. We calculated the comorbidity-adjusted LE (CaLE) estimated with Cox proportional hazards modeling. Secondary analysis was performed on a contemporary population (2004-2009) to allow for incorporation of D'Amico risk stratification. RESULTS The study cohort included 46,376 men of which 17,873 received pADT (39%). Relative to observation, pADT was associated with a survival disadvantage, hazard ratio for all cause mortality 1.37 (95%CI: 1.20-1.56). In the 2004-2009 population the adverse affect of pADT was also demonstrated, HR 1.48 (95%CI: 1.12-1.95). The adverse effect of pADT was most pronounced in men with CaLE > 10 years (figure1). Results for the sub-population analysis are presented in table 1. CONCLUSIONS For men forgoing primary definitive therapy, the use of pADT is not associated with a survival benefit compared to observation, and denies men an opportunity for curative treatment. The deleterious effect of pADT is most pronounced in men with prolonged LE. Table 1. Adjusted risk of all cause mortality for men undergoing primary androgen deprivation therapy, relative to observation for localized and locally advanced prostate cancer, stratified by life expectancy and disease severity. SEER–Medicare 1992-2009 Standard Cox model Co-Morbidity Adjusted life expectancy Under 5 years 5-10 years Over 10 years HR (95%CI) p-value HR (95%CI) p-value HR (95%CI) p-value T1/T2 Low Risk* 0.95 (0.83-1.09) 0.5 1.11 (1.06-1.17) <0.001 1.39 (1.32-1.46) <0.001 T1/T2 High Risk* 0.91 (0.79-1.04) 0.16 1.17 (1.10-1.25) <0.001 1.51 (1.41-1.63) <0.001 T3 0.54 (0.3-0.98) 0.04 1.26 (1.06-1.51) 0.01 1.98 (1.74-2.27) <0.001 Propensity weighted Cox proportional hazards model+ Co-Morbidity Adjusted life expectancy Under 5 years 5-10 years Over 10 years HR (95%CI) p-value HR (95%CI) p-value HR (95%CI) p-value T1/T2 Low Risk* 0.96 (0.84-1.1) 0.6 1.1 (1.05-1.16) <0.001 1.36 (1.28-1.44) <0.001 T1/T2 High Risk* 0.85 (0.75-0.98) 0.02 1.11 (1.04-1.18) 0.001 1.46 (1.35-1.57) <0.001 T3 0.79 (0.49-1.29) 0.3 1.27 (0.94-1.35) 0.2 1.78 (1.56-2.04) <0.001 Abbreviations: HR, hazard ration; CI, confidence interval; pADT, primary androgen deprivation therapy +-Covariates included age at diagnosis, year at diagnosis, race, marital status, population density, census tract income and educational attainment, Charleson Comorbidity Index & pADT percent in patient’s HSA. *- Prior to 2003 Gleason grade of 2-4, 5-7, and 8-10 corresponded to well-differentiated (AJCC grade 1), moderately (AJCC grade 2) differentiated, and poorly differentiated disease (AJCC grade 3), respectively. Thereafter a Gleason grade of 2-4, 5-6, and 7-10 corresponded to well-differentiated, moderately differentiated, and poorly differentiated CaP. Well and moderately differentiated cancers constitute the low risk group. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e937-e938 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jesse Sammon More articles by this author Firas Abdollah More articles by this author Gally Reznor More articles by this author Daniel Pucheril More articles by this author Akshay Sood More articles by this author Dane Klett More articles by this author Julian Hanske More articles by this author Christian Meyer More articles by this author Mani Menon More articles by this author Quoc-Dien Trinh More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Testing the Dividend Pricing Hypothesis in Housing Markets: The Role of Risk

Tests of the dividend pricing hypothesis (DPH) applied to housing have stud- ied the trade-obetween the capitalization rate (CAP rate) and subsequent house price appreciation. Even allowing for the fact that actual appreciation does not equal expected appreciation, evidence for the DPH is not strong. This research has included an implicit assumption that risks associated with housing investment are common across housing markets. In addition, many previous tests have used the Bureau of Labor Statistics (BLS) Rental Index to construct the CAP rate although recent research by Ambrose, Coulson and Yoshida (2013) has questioned this data. We use the American Housing Survey to construct estimates of the CAP rate which is then combined with standard appreciation measures to estimate total return and its variance over time for larger U.S. MSAs. Adding risk measures to a test of the DPH produces results consistent with the DPH. However, when the BLS Rent Index is used to measure CAP rates and risk, the results are not consistent with DPH. Overall, it appears that using statistically constructed estimates of the CAP rate and adding variance in total return to tests of the DPH produces far stronger results than those obtained in previous studies.

Relación de las profesiones y las condiciones laborales con la neumonía adquirida en la comunidad

IntroductionCommunity-acquired pneumonia (CAP) is not considered a professional disease, and the effect of different occupations and working conditions on susceptibility to CAP is unknown. The aim of this study is to determine whether different jobs and certain working conditions are risk factors for CAP. MethodologyOver a 1-year period, all radiologically confirmed cases of CAP (n=1,336) and age- and sex-matched controls (n=1,326) were enrolled in a population-based case-control study. A questionnaire on CAP risk factors, including work-related questions, was administered to all participants during an in-person interview. ResultsThe bivariate analysis showed that office work is a protective factor against CAP, while building work, contact with dust and sudden changes of temperature in the workplace were risk factors for CAP. The occupational factor disappeared when the multivariate analysis was adjusted for working conditions. Contact with dust (previous month) and sudden changes of temperature (previous 3 months) were risk factors for CAP, irrespective of the number of years spent working in these conditions, suggesting reversibility. ConclusionSome recent working conditions such as exposure to dust and sudden changes of temperature in the workplace are risk factors for CAP. Both factors are reversible and preventable.

Reflex PCA3 messenger ribonucleic acid testing: validation of postbiopsy urine samples and correlation with prostate biopsy findings in ∼2000 patients.

To validate post-transrectal ultrasonography (TRUS) prostate biopsy (bx) urine samples for PCA3 messenger ribonucleic acid testing, including correlation of PCA3 score with concurrent bx findings. From July 2008 to July 2010, 2015 patients had urine collected immediately after a TRUS-guided prostate bx. Excluded were men with history of prostate carcinoma (CaP), <6 or ≥24 bx cores, and/or prostate-specific antigen (PSA) level ≥50 ng/mL, resulting in 1909 included men. PCA3 and PSA messenger ribonucleic acid were quantitated using transcription-mediated amplification. A PCA3 score of ≥35 was considered positive. Mean and median ages were 66 years. Mean and median PSA levels were 6.7 and 5.1 ng/mL, respectively. Bxs were benign in 970 (50.8%), CaP in 726 (38%), high-grade prostatic intraepithelial neoplasia (HGPIN) in 124 (6.5%), and atypical in 89 (4.7%). PCA3 test was informative in 1887 (98.8%) patients. Means ± standard deviations (median) of PCA3 scores for benign, HGPIN, atypical, and CaP were 22.3 ± 27.9 (12.8), 37.6 ± 43.2 (24.1), 35.7 ± 36.2 (25.7), and 46.9 ± 48.1 (31.6; P <.05 benign vs CaP, benign vs HGPIN and atypical, HGPIN and atypical vs CaP). Sensitivity and specificity of PCA3 for CaP were 46.3% and 78.7%, respectively. CaP risk increased with progressively higher PCA3 score ranges from 14.8% for PCA3 <5 to 66.7% for PCA3 >100. Area under the curve (AUC) for the PCA3 receiver operating characteristics was not significantly different in men without prior bx (AUC = 0.716) compared with men with at least 1 prior nonpositive bx (AUC = 0.702). Post-TRUS bx urine is a valid sample for PCA3 testing. Patients with a negative bx and a positive PCA3 test may have a higher likelihood of unsampled CaP.

Coupling of prostate and thyroid cancer diagnoses in the United States.

Prostate and thyroid cancers represent two of the most overdiagnosed tumors in the US. Hypothesizing that patients diagnosed with one of these malignancies were more likely to be diagnosed with the other, we examined the coupling of diagnoses of prostate and thyroid cancer in a large US administrative dataset. The surveillance, epidemiology, and end results (SEER) database was used to identify men diagnosed with clinically localized prostate cancer (CaP) or thyroid cancer between 1995 and 2010. SEER*stat software was used to estimate multivariable-adjusted standardized incidence ratios (SIRs) and investigate the rates of subsequent malignancy diagnosis. Additional non-urologic cancer sites were added as control groups. Patients with thyroid cancer were much more likely to be diagnosed with CaP than patients in the SEER control group (SIR 1.28 [95% CI 1.1-1.5]; p < 0.05). Similarly, the observed incidence of thyroid cancer was significantly higher in patients with CaP when compared with SEER controls (SIR 1.30 [95% CI 1.2-1.4]; p < 0.05). When stratified by follow-up interval, the observed thyroid cancer diagnosis rate among men with CaP was significantly higher than expected at 2-11 (SIR 1.83 [95% CI 1.4-2.4]), 12-59 (SIR 1.24 [95% CI 1.0-1.5]), and 60-119 (SIR 1.25 [95% CI 1.0-1.5]) months of follow-up. There was no increased risk of CaP or thyroid cancer diagnosis among patients with non-urologic malignancies. There is a significant association of diagnoses with prostate and thyroid cancer in the US. In the absence of a known biological link between these tumors, these data suggest that diagnosis patterns for prostate and thyroid malignancies are linked.

Using MRI/ultrasound fusion biopsy to detect clinically significant prostate cancer in the African American population.

57 Background: African-American (AA) men are at greater risk for prostate cancer (CaP) and experience increased prostate cancer-specific mortality. We aimed to determine racial disparities in CaP incidence, pathology, and anatomy identified on MRI/US fusion biopsy. Methods: Patients who underwent MP-MRI with targeted MRI/US fusion biopsy at our institution between May 2007 and June 2013 were reviewed. AA patients undergoing fusion biopsy were matched by age and PSA with a Caucasian cohort at a 1:2 ratio. MRI and pathologic parameters including lesion location, number of lesions, and Gleason score. Bivariate comparisons were made with the Student’s t-test and Χ2 analysis. Results: 822 patients had MRI/US fusion biopsy. 127 AA men were paired with a matched cohort of 254 Caucasians. Mean age was 60.2 and 61.4 years and mean PSA was 11.6 and 10.7ng/ml in AAs and Caucasians, respectively. We identified significantly more AA with CaP (49.6% vs 37.4%, p=0.03; Table). AAs also had higher grade disease (Gleason 7-10) versus white men (20.5% vs. 11.8%, p=0.04). Additionally, the diagnostic yield for the AA cohort was significantly higher per sampled lesion (37.5% vs 24.5%, p&lt;0.01), despite no significant differences in % core involvement of the highest risk lesion between the groups. While there was no significant difference in presence of anterior lesions between the groups (15.7% vs 12.9%, p=NS), anterior lesions equally represented the highest risk lesions in both cohorts. Conclusions: MRI/US Fusion-guided biopsy demonstrates increased diagonostic yield/incidence of CaP and higher risk disease in the AA population in an age and PSA matched cohort of Caucasian patients. [Table: see text]

Admixture mapping of prostate cancer in African Americans participating in the North Carolina-Louisiana Prostate Cancer Project (PCaP).

Few genetic risk factors have been uncovered that contribute specifically to the racial disparity in prostate cancer (CaP) observed in African Americans (AA). With the advent of ancestry informative marker (AIM) single nucleotide polymorphism (SNP) panels and powerful genetic strategies such as mapping by admixture linkage disequilibrium (MALD) it is possible to discover genes that underlie ethnic variation in disease risk. One thousand one hundred thirty AA CaP cases enrolled in the North Carolina-Louisiana Prostate Cancer Project (PCaP) were genotyped using a 1,509 AIM SNP panel. MALD was performed using ADMIXMAP to test for linkage between CaP risk and ancestry estimates at each AIM SNP. The largest increase of African ancestry was observed at marker rs12543473 (P = 0.0011), located on chromosome 8q24.21, and the greatest excess of European ancestry was observed at marker rs10768140 (P = 0.0004) at chromosome 11p13. The study confirmed the 8q24 risk loci and identified a novel genomic region on 11p13 that is associated with CaP risk. These findings should be replicated in larger AA populations and combined with fine mapping data to further refine the novel 11p13 CaP risk loci.

Community-Acquired Pneumonia and Proton Pump Inhibitors

The Authors' Reply: In our study, “Confounding in the Association of Proton Pump Inhibitor Use With Risk of Community-Acquired Pneumonia,” we found that use of PPIs was associated not only with higher rates of community-acquired pneumonia, but also higher rates of other infectious and non-infectious conditions such as urinary tract infection and deep venous thrombosis. We interpreted these multiple associations as demonstrating selection bias among those using PPIs rather than a causal effect of PPI use on pneumonia, as has been argued extensively. Rysavy and colleagues raise the important objection that we did not report whether PPI use preceded a diagnosis of pneumonia, which is important since a temporal association is a pre-requisite for any causal interpretation of an empirical association. While their point is valid, several points are worth noting. First, our estimated odds ratios of the association between PPI use and pneumonia were similar to those reported in previous studies, suggesting this timing issue may be more important in theory than in practice. Second, in unreported analysis, we restricted cases of pneumonia and other conditions among PPI users to only include those that occurred after a prescription for a PPI had been filled, which is similar to what Rysavy and colleagues suggest. Doing so did not affect our basic finding that PPI use is associated with multiple disease diagnoses even within the same individual compared over time during periods of PPI use and non-use. Third, the demonstration in other studies that PPI use is associated with higher temporally subsequent rates of pneumonia is not convincing alone. Individuals change over time and trends in disease states or social factors that lead an individual to be prescribed a PPI may also be correlated with future risk of pneumonia. This association may not reflect a causal impact of PPI use on pneumonia, but rather trends in health or provider behavior that are unobserved by the analyst and that are correlated with both PPI use and subsequent pneumonia risk. Norris eloquently summarizes the intuition behind our falsification approach, and, with some caveats, we agree with the general principle he articulates. The main thrust behind Norris’s argument is that falsification endpoints such as urinary tract infection, skin infection, osteoarthritis, chest pain, and so on, cannot be chosen arbitrarily. Indeed, demonstrating that PPI use is not associated with a completely arbitrary, randomly chosen variable (e.g., hair color) would not be an appropriate falsification endpoint since there is no known causal mechanism by which hair color might affect both the risk of CAP to a patient and his probability of being prescribed a PPI. A falsification hypothesis is only useful if it assesses a specific mechanism of confounding, in our case, selection on the basis of unobserved health risks, patient socioeconomic characteristics, or physician attributes, all of which may be associated with both PPI use and risk of CAP. Falsification tests that do not test a specific mechanism of confounding offer little, since they cannot suggest whether selection on unobserved variables is likely to be causing the observed association between a treatment (PPI use) and an outcome of interest (CAP). It is reasonable to question whether osteoarthritis and chest pain would be appropriate falsification outcomes given this discussion. While osteoarthritis is a chronic condition, whereas CAP is acute, identifying an association between PPI use and osteoarthritis tests a specific mechanism of confounding, patients who are more likely to see a physician and be diagnosed with a condition such as an osteoarthritis flare are also more likely to be prescribed a PPI (as well as other medications) and diagnosed with CAP (as well as other conditions). Our opinion is that this access to care (or more generally, access to a diagnosis) may be an important source of confounding beyond the pure physiologic effect of health risks on the risk of CAP. We agree with Norris that chest pain may be endogenous in that a diagnosis of chest pain may prompt an empiric treatment with a PPI. It would therefore not be an ideal falsification test since the association between chest pain and PPI use may not reflect a specific method of confounding. With that said, we find positive falsification tests with a series of additional outcomes including deep venous thrombosis, urinary tract infection, and cellulitis. We agree with both sets of authors that falsification analyses (or ‘specificity criterion’) are but one tool to help determine causality in observational studies. We view falsification testing not as a substitute for rigorous observational study designs, but as a necessary complement. More broadly, observational studies in medicine should more frequently attempt to search for plausibly exogenous sources of variation in treatment (e.g., natural experiments) to help identify causal relationships. For instance, one may consider using variation in health plan coverage of particular medications as a source of treatment ‘randomization.’

Androgenetic alopecia at various ages and prostate cancer risk in an equal-access multiethnic case–control series of veterans

Epidemiological data are conflicting regarding the association between androgenetic alopecia (AA) and prostate cancer (CaP). We examined the relationship between these two conditions. We performed a case-control study at a Veterans Affairs Hospital among 708 men: 312 healthy controls, 167 men with CaP, and 229 men without CaP on prostate biopsy. Participants were asked to self-describe hair patterns at ages 30 and 40 and at study enrollment. We tested the association between hair pattern (overall, vertex, or frontal) and CaP status using logistic regression analysis adjusting for multiple clinical features. Disease grade was similarly examined as a secondary outcome. Relative to healthy controls, younger age of AA onset was significantly associated with increased CaP risk (p = 0.008). Similar patterns were noted for frontal (p = 0.005) and not vertex balding (p = 0.22). When compared with biopsy-negative men, a similar pattern was seen with younger age of AA onset having higher risk of CaP, though this was not significant (p = 0.07). A suggestion for younger age of AA onset for frontal (p = 0.07) being associated with CaP versus biopsy-negative men was also observed. Overall balding (yes/no) was associated with greater than twofold increase in high-grade disease (p = 0.02). Men reporting earlier AA onset were at increased CaP risk and suggestively had more aggressive disease. Contrary to other studies, frontal balding was the predominant pattern associated with elevated CaP risk. Further study is required to confirm these findings in a larger sample and to better understand the role of AA, androgens, and CaP biology.

Association between exercise and primary incidence of prostate cancer

Exercise is a modifiable lifestyle risk factor associated with prostate cancer risk reduction. However, whether this association is different as a function of race is unclear. In the current study, the authors attempted to characterize the link between exercise and prostate cancer (CaP) in white and black American men. Using a prospective design, 307 men (164 of whom were white and 143 of whom were black) who were undergoing prostate biopsy completed a self-reported survey that assessed exercise behavior (metabolic equivalent [MET] hours per week). Crude and adjusted logistic regression analyses were used to estimate the risk of prostate cancer controlling for age, body mass index, digital rectal examination findings, previous biopsy, Charlson comorbidity score, and family history of CaP stratified by self-reported race. There was no significant difference noted with regard to the amount of exercise between racial groups (P = .12). Higher amounts of MET hours per week were associated with a decreased risk of CaP for white men in both crude (P = .02) and adjusted (P = .04) regression models. Among whites, men who exercised ≥ 9 MET hours per week were less likely to have a positive biopsy result compared with men exercising < 9 MET hours per week (odds ratio, 0.47; 95% confidence interval, 0.22-0.99 [P = .047]). There was no association noted between MET hours per week and risk of CaP among black men in both crude (P = .79) and adjusted (P = .76) regression models. In a prospective cohort of men undergoing biopsy, increased exercise, measured as MET hours per week, was found to be associated with CaP risk reduction among white but not black men. Investigating race-specific mechanisms by which exercise modifies CaP risk and why these mechanisms disfavor black men in particular are warranted.

Serum levels of chromogranin A are not predictive of high-grade, poorly differentiated prostate cancer: Results from an Italian biopsy cohort

ObjectivesTo explore the association of chromogranin A (CgA) levels and the risk of poorly differentiated prostate cancer (CaP) in men undergoing prostate biopsy. Materials and methodsBetween 2006 and 2012, we prospectively enrolled 1,018 men with no history of CaP undergoing prostate biopsy. The risk of detecting poorly differentiated CaP as a function of CgA concentration was evaluated using crude and adjusted logistic regressions. Further analyses were performed to determine whether CgA was a significant predictor of high-grade CaP in men with low PSA (<10 ng/ml). ResultsWe found a significantly higher level of CgA in men with poorly differentiated CaP. CgA was however co-linear with age, and serum CgA levels were not significantly associated with the overall risk of CaP, and the specific risk of poorly differentiated CaP (OR 1.001 95% CI 0.99–1.01, P = 0.74). Moreover, in men with low PSA levels (<10 ng/ml), CgA was not a significant predictor of high grade-disease on univariate (OR 1.00; 95% CI 0.99–1.01; P = 0.66) and multivariate analysis (P = 0.85). ConclusionsIn our cohort of patients, the serum level of CgA is not a significant predictor of poorly differentiated CaP on initial prostate biopsy, even in men with low PSA levels (<10 ng/ml). According to our experience, CgA should not be considered a reliable marker to predict poorly differentiate cancer in the setting of initial prostate biopsy.

Association of Androgen Receptor, Prostate-Specific Antigen, andCYP19Gene Polymorphisms with Prostate Carcinoma and Benign Prostatic Hyperplasia in a North Indian Population

The genes involved in androgen pathway and metabolism have been reported to contribute considerably to prostate carcinoma (CaP) risk. The present study investigated the association of androgen receptor (AR), prostate-specific antigen (PSA or KLK3), and cytochrome P450 (CYP19) gene polymorphisms in CaP (n=105) and benign prostatic hyperplasia (BPH) (n=120) in comparison to normal healthy controls (n=106) in an Indian population. We also evaluated the functional consequences of these gene variants on AR and PSA mRNA expression. Significant association of short AR CAG repeats (≤24) with risk of CaP (odds ratios [OR]=2.98, p<0.001) and BPH (OR=1.96, p=0.01) was observed; however, CYP19 gene polymorphism was not found to be associated with disease phenotype (p>0.05). PSA G-158A SNP was found to be significantly associated with risk of CaP (AA: OR=2.68, p=0.016 and GA: OR=2.07, p=0.018) p-trend 0.031 and BPH (AA: OR=3.46, p<0.001 and GA: OR=2.47, p=0.03) p-trend 0.009, respectively. PSA G-158A genotype independently increased the risk of developing BPH (OR=16.37, p<0.001), irrespective of AR CAG repeat length. Using quantitative real-time polymerase chain reaction, we found a significant upregulation of AR and PSA mRNA expression in CaP comparison to BPH. While short AR CAG (≤24) repeats were associated with higher AR mRNA expression in CaP (p=0.002), the PSA SNP did not correlate with its mRNA expression. Interestingly, significantly higher risk estimates for CaP were observed for the combined analysis of short AR CAG and CYP19 genotypes (A2A2) (OR=7.18, p<0.001) or A2A3 (OR=7.60, p=0.004). Our results suggest significant association of androgen signaling gene polymorphisms with risk of CaP and BPH and provide evidence for a putative functional role of AR CAG repeat in regulating its mRNA expression and warrant the need of larger studies in the Indian population to confirm our results.

Coffee Consumption and Prostate Cancer Aggressiveness Among African and Caucasian Americans in a Population-Based Study

This study evaluated the relationship between caffeinated and decaffeinated coffee and prostate cancer (CaP) aggressiveness using data from a population-based incident CaP study within the North Carolina-Louisiana Prostate Cancer Project (PCaP). Classification of CaP aggressiveness at diagnosis was based on clinical criteria for 1,049 African-American (AA) and 1,083 Caucasian-American (CA) research subjects. Coffee consumption was measured using a modified NCI Dietary History Questionnaire. No significant associations were found between CaP aggressiveness and consumption of either caffeinated or decaffeinated coffee. The OR for high aggressive CaP among consumers of more than 4 cups per day was 0.92 (95%CI = 0.61, 1.39), compared to non-coffee-drinkers. Results stratified by race found no significant associations and no noticeable trends in either AAs (P for trend = 0. 62) or CAs (P for trend = 0.42). In contrast to a recent report on a select population that has less complete information on CaP aggressiveness suggesting that coffee prevents aggressive CaP, this rapid case ascertainment population-based study, in a biracial population with differing risks of CaP did not demonstrate a protective relationship between high coffee consumption and risk of high aggressive CaP.

8q24 and 17q Prostate cancer susceptibility loci in a multiethnic Asian cohort

ObjectivesRecently, several genome-wide association studies have demonstrated a cumulative association of 5 polymorphic variants in chromosomes 8q24 and 17q with prostate cancer (CaP) risk in Caucasians, particularly those harboring aggressive clinicopathologic characteristics. The purpose of this study was to evaluate the influence of these variants on CaP susceptibility in Singaporean Asian men. Materials and methodsWe performed a case-control study in 289 Chinese CaP patients and 412 healthy subjects (144 Chinese, 134 Malays, and 134 Indians), and examined the association of the 5 single nucleotide polymorphisms (SNPs) with CaP. ResultsIn the healthy subjects, rs16901979 A-allele frequency was highest amongst Chinese (0.32) compared with Malays (0.13; P < 0.0001) or Indians (0.09; P < 0.0001); rs6983267 G-allele was highest in Indians (0.51) compared with Chinese (0.42; P = 0.041) or Malays (0.43; P = 0.077); whereas rs1859962 G-allele frequency was highest amongst Indians (0.56) compared with Chinese (0.40; P = 0.0002) or Malays (0.38; P < 0.0001). Individuals with the rs4430796 TT genotype were at increased CaP risk in the Chinese via a recessive model (odds ratios (OR) = 1.56, 95% CI = 1.04–2.33). Significant associations were observed for rs4430796 TT with Gleason scores of ≥7 (OR = 1.76, 95% CI = 1.14–2.73) and prostate-specific antigen (PSA) levels of ≥10 ng/ml at diagnosis (OR = 1.63, 95% CI = 1.01–2.63), as well as for rs6983267 GG with stage 3–4 CaPs (OR = 1.91, 95% CI = 1.01–3.61). A cumulative gene interaction influence on disease risk, which approximately doubled for individuals with at least 2 susceptibility genotypes, was also identified (OR = 2.18, 95% CI = 1.10–4.32). ConclusionsThis exploratory analysis suggests that the 5 genetic variants previously described may contribute to prostate cancer risk in Singaporean men.

The risk of biopsy-detectable prostate cancer using the prostate cancer prevention Trial Risk Calculator in a community setting

Materials and methodsRisks of prostate cancer (CaP) and high-grade CaP were evaluated using the Prostate Cancer Prevention Trial Risk Calculator (PCPTRC) in an age-stratified random sample of 1,021 Caucasian and African-American men with no previous diagnosis of CaP, aged 55–74 years, residing in King County, WA, USA. ResultsMedian PCPTRC risks of CaP (high-grade CaP) were 15.6% (1.2%), 18.7% (2.0%), 18.5% (2.2%), and 26.4% (5.1%) for 55–59, 60–64, 65–69, and 70–74-year-old men, respectively; 25.2% of men aged 55–59 had a 25% or greater PCPTRC risk of CaP; this increased to 53.1% in men aged 70–74; 9.4% of men aged 55–59 had a 6% or greater PCPTRC risk of high-grade CaP, increasing to 44.1% in men aged 70–74. ConclusionsPCPTRC risk of CaP in a community of US males is high and confounded with overdetected cancers. In contrast, average community PCPTRC risk of high-grade disease is low and increases gradually by age and may better serve for counseling purposes.

Heavy ethanol intake and elevated prostate cancer risk among men with previous negative biopsies in the REDUCE trial.

187 Background: Whether ethanol intake contributes to prostate cancer (CaP) risk is debated. Although ethanol was found to contribute to increased CaP risk in the Prostate Cancer Prevention Trial, whether ethanol intake impacts CaP risk among men with previous negative biopsies has not been previously assessed. We therefore examined the relationship between ethanol consumption and CaP risk in the REDUCE trial and further sought to determine whether ethanol intake modifies the effect of dutasteride in reducing CaP risk. Methods: This is secondary analyses using data from 6,729 men who had at least one on-study biopsy while participating in the REDUCE trial. Ethanol intake, which was expressed as units (½ pint of beer or 1 glass of wine, etc.) per week, was analyzed as a continuous and three-tiered categorical variable [non-drinker, moderate (≤7 units/week), heavy-drinker (&gt;7 units/week)]. Risks for overall and high-grade (Gleason ≥7 vs. Gleason&lt;7 CaP or biopsy negative) CaP were evaluated using logistic regression adjusting for clinical parameters including dutasteride intake. Test for interaction was used to determine whether the association between dutasteride and CaP risk is influenced by ethanol. Results: Forty-nine percent were moderate-drinkers and 26% were heavy-drinkers. On a continuum, increased ethanol intake was significantly associated with elevated risk for overall (p=0.035) and high-grade CaP (p=0.048). Compared to non-drinkers, heavy drinkers were at increased risk for overall (OR 1.21; 95% CI 1.02-1.43; p=0.03) and high-grade CaP (OR 1.34; 95% CI 1.01-1.78; p=0.04). Risks for overall (p=0.55) and high-grade CaP (p=0.21) were comparable between moderate- and non-drinkers. Dutasteride reduced overall CaP risk (OR 0.73; p&lt;0.001) and ethanol intake did not modify the effect of dutasteride on CaP incidence (p-interaction=0.64). Conclusions: Among low-risk men with at least one prior negative prostate biopsy, heavy ethanol intake is associated with increased risk for overall and high-grade CaP. In contrast to CaP prevention with finasteride, which appears to be inhibited by heavy ethanol intake, consumption of ethanol does not negatively impact CaP prevention with dutasteride.

Physical activity and prostate cancer risk reduction: Does race matter?

235 Background: We previously reported that physical activity may reduce prostate cancer (CaP) risk among men undergoing prostate biopsy. However, whether the potential benefit of exercise against cancer differs by race is unclear. We therefore sought to further characterize the link between physical activity and CaP risk as a function of race. Methods: Men undergoing prostate biopsy at the Durham VA Hospital were asked to complete a survey assessment of current exercise habits including frequency of differing intensities (mild, moderate and strenuous) as well as the average duration. Total current exercise was calculated by multiplying the frequency of sessions within each intensity by their average duration, weighted by the estimated metabolic equivalent (MET) and then summed across all intensities expressed as average total MET hrs/wk. Specifically, exercise intensities were as follows: mild (3 METs, e.g. easy walking), moderate (5 METs, e.g. tennis), and strenuous (9 METs, e.g. running). Quantified exercise was compared between race groups using rank sum test. Associations between exercise and CaP risk was determined using crude and adjusted logistic regression stratified by race. Results: A total of 308 men had complete data for analysis. Of these men, 53% were white and 47% were black. There was no significant difference in the amount of physical activity between race groups (p= 0.11). Increased amount of exercise was associated with decreased CaP risk for white men in both crude (OR= 0.89; 95% CI=0.81–0.98; p=0.02) and adjusted (OR=0.90; 95% CI=0.82−0.99; p=0.04) regression models that controlled for age, BMI, DRE, previous biopsy, and family history of CaP. We found no association between exercise and CaP risk among black men in both crude (p=0.79) and adjusted regression models (p=0.87). Conclusions: Increased physical activity was associated with CaP risk reduction among white men but not among black men. Further investigations to validate this potential source of CaP race disparity and to identify exercise-specific parameters that influence CaP risk reduction (ex. age-specific or cumulative exercise) are required. Investigating the race-specific mechanisms through which exercise modifies CaP risk is also warranted.

Genetic variants in antioxidant genes, Gleason grade, and prostate cancer recurrence after radical prostatectomy.

33 Background: Laboratory and genomic data suggest that the antioxidant defense system is important in prostate carcinogenesis, and that this relation may vary by plasma antioxidant status. Methods: Among 567 radical prostatectomy (RP) patients with non-metastatic prostate cancer (CaP), we examined genetic variants in SOD1(5 SNPs), SOD2(6), SOD3(6), TXRND1(5), TXRND2(21), GPX1(3), GPX3(8), GPX4(5), CAT(9), XRCC1(2), SELENBP1(5), SEP15(4), SEPP1(4), SEC14L2(8), and TTPA(4) and risk of high pathologic Gleason sum (8+ or 7 with primary 4+) using logistic regression, and CaP recurrence (PSA rise, second treatment, metastasis) using Cox proportional hazards regression. We also examined whether the genetic variants interacted with plasma selenium, alpha-tocopherol, or gamma-tocopherol in relation to risk of high grade CaP. Results: 21% (n = 117) of men had high grade CaP, and 47 recurrences occurred (median follow-up of all participants = 3 y). Men with 1+ of the less common allele (CT or TT) in rs4880 (SOD2) had a 49% reduced rate of recurrence (hazard ratio (HR): 0.51; 95% confidence interval (CI): 0.28, 0.92), independent of grade, stage, and PSA. In contrast, men with 1+ of the less common allele in 3 of the TXRND1, 4 of the TXRND2, and 1 of the SEP15 SNPs had 2-fold increased rate of recurrence (HRs: 1.93-2.95; p-values: 0.002-0.04), and men with 2 of the less common allele in 2 of the GPX3 SNPs had 3-fold increased rate of recurrence (p-values from additive models: &lt;0.01). For high grade CaP, men with 1+ of the less common allele in 1 of the SOD3 SNPs or 2 of the less common alleles in 2 of the TXRND2 SNPs had 2-fold increased risk (p-values = 0.007-0.02), while men with 1+ of the less common allele in 1 of the GPX1 SNPs had 37% reduced risk (p-value = 0.04). Among men with certain genotypes in 3 TXRND2, 1 GPX3, or 2 CAT SNPs, high plasma selenium reduced risk of high grade CaP by 50-76%. Among men with certain genotypes in 1 SOD1 or 1 SOD2 SNP, high plasma alpha-tocopherol reduced risk of high grade CaP by 65-68%. Conclusions: Genetic variants in antioxidant genes may be associated with CaP recurrence after RP, and may interact with plasma selenium and alpha-tocopherol in relation to risk of high grade CaP.