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ABSTRACT: PURPOSE: Inflammation may play a role in the development and progression of many cancers, including prostate cancer. We sought to test whether histological inflammation within prostate cancer was associated with more aggressive disease. METHODS: The slides of prostatectomy specimens were reviewed by a board-certified pathologist on 287 men from a Veterans Affairs Medical Center treated with radical prostatectomy from 1992 to 2004. The area with the greatest tumor burden was scored in a blinded manner for the degree of inflammation: absent, mild, or marked. We used logistic and Cox proportional hazards regression analysis to examine whether categorically coded inflammation score was associated with adverse pathology and biochemical progression, respectively. RESULTS: No inflammation was found in 49 men (17 %), while 153 (53 %) and 85 (30 %) had mild and marked inflammation. During a median follow-up of 77 months, biochemical recurrence occurred among 126 (44 %) men. On multivariate analysis, more inflammation was associated with greater risk of positive margins, capsular penetration, and seminal vesicle invasion (all p < 0.05). Marked inflammation was associated with increased PSA recurrence risk when adjusting for preoperative features only (HR 2.08, 95 % CI 1.02-4.24), but not after adjusting for pathologic features. CONCLUSIONS: Inflammation within prostate cancer was associated with more advanced disease, although it is unclear whether aggressive disease caused increased inflammation or inflammation caused aggressive disease.
World Journal of Urology 04/2013; · 2.41 Impact Factor
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Jean-Alfred Thomas,
Jodi A Antonelli,
Lionel L Banez,
Catherine Hoyo,
Delores Grant,
Wendy Demark-Wahnefried,
Elizabeth A Platz, Leah Gerber,
Kathryn Shuler,
Enwono Eyoh,
Elizabeth Calloway,
Stephen J Freedland
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ABSTRACT: PURPOSE: Epidemiological data are conflicting regarding the association between androgenetic alopecia (AA) and prostate cancer (CaP). We examined the relationship between these two conditions. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.
Cancer Causes and Control 03/2013; · 2.88 Impact Factor
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ABSTRACT: BACKGROUND: Although obesity has been associated with larger prostate volumes (PV), few studies have actually investigated whether obesity enhances PV growth, especially among men using 5α-reductase inhibitors. OBJECTIVE: To examine whether obesity is associated with enhanced PV growth measured by serial transrectal ultrasound (TRUS) measurements. DESIGN, SETTING, AND PARTICIPANTS: We conducted a secondary analysis of the REduction by DUtasteride of prostate Cancer Events (REDUCE) trial, which was originally aimed at cancer risk reduction among high-risk men with a single negative prestudy biopsy. INTERVENTION: Per-protocol randomization to placebo or dutasteride and mandatory TRUS-guided biopsies at 2 yr and 4 yr. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Percentage change in PV at 2 yr and 4 yr from baseline. We tested its association with baseline body mass index (BMI) groups of <25, 25-29.9, and ≥30kg/m(2) using multivariable linear regression. Secondarily, we tested whether BMI was associated with the likelihood of having no PV reduction among men randomized to dutasteride using multivariable logistic regression. RESULTS AND LIMITATIONS: Of 8122 participants, we analyzed 71.8% and 54.5% with complete 2-yr and 4-yr PV data, respectively. In multivariable analysis, men on placebo with BMI ≥30 versus <25kg/m(2) had enhanced PV growth from baseline (at 2 yr: 17.0% vs 10.7%, p<0.001; at 4 yr: 29.4% vs 20.1%; p=0.001). Men on dutasteride with BMI ≥30 versus <25kg/m(2) had attenuated PV reduction from baseline (at 2 yr: -14.3% vs -18.5%; p=0.002; at 4 yr: -13.2% vs -19.3%; p=0.001) and higher likelihood of having no PV reduction (at 2 yr: odds ratio [OR]: 1.44; 95% confidence interval [CI], 1.08-1.93; p=0.014; at 4 yr: OR: 1.62; 95% CI, 1.18-2.22; p=0.003). We found no significant interactions between BMI and dutasteride on PV change at 2 yr and 4 yr (p interaction ≥0.36). No clinical outcomes or effects of weight change were assessed. CONCLUSIONS: Obesity enhanced PV growth and attenuated PV reduction by dutasteride. The null interaction between obesity and dutasteride for PV change implies that the effect of obesity on dutasteride-treated men is likely a combination of dutasteride-driven PV reduction with obesity-driven PV growth rather than decreased dutasteride efficacy. CLINICALTRIALS.GOV IDENTIFIER: NCT00056407.
European urology 03/2013; · 7.67 Impact Factor
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ABSTRACT: BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. Cancer 2013. © 2013 American Cancer Society.
Cancer 02/2013; · 4.77 Impact Factor
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Delores J Grant,
Cathrine Hoyo,
Shannon D Oliver, Leah Gerber,
Katie Shuler,
Elizabeth Calloway,
Alexis R Gaines,
Megan McPhail,
Jonathan N Livingston,
Ricardo M Richardson,
Joellen M Schildkraut,
Stephen J Freedland
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ABSTRACT: Aims: Uridine diphosphate-glucuronosyltransferase 2B (UGT2B) enzymes conjugate testosterone metabolites to enable their excretion in humans. The functional significance of the UGT2B genetic variants has never been described in humans. We evaluated UGT2B variants in relation to plasma androstane-3α,17β-diol-glucuronide (AAG) levels and the prostate cancer risk. Results: AAG levels were measured in sera from 150 controls and compared to the polymorphisms of UGT2B17, UGT2B15, and UGT2B7. Genomic DNA from controls (301) and cases (148) was genotyped for the polymorphisms, and odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using unconditional logistic regression analyses. Having two copies of UGT2B17 was associated with higher AAG levels in controls among Whites (p=0.02), but not Blacks (p=0.82). Logistic regression models adjusting for age and race revealed that homozygosity for the G allele of the UGT2B15(D85Y) polymorphism was directly associated with the prostate cancer risk (OR=2.70, 95% CI=1.28, 5.55). Conclusions: While the small sample size limits inference, our findings suggest that an association between the UGT2B17 copy number variant (CNV) and serum AAG levels in Whites, but unexpectedly not in Blacks. This novel observation suggests that genetic determinants of AAG levels in Blacks are unrelated to the UGT2B17 CNV. This study replicates the results that show an association of UGT215(D85Y) with an increased prostate cancer risk.
Genetic Testing and Molecular Biomarkers 10/2012; · 1.11 Impact Factor
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ABSTRACT: Obesity is associated with an increased risk of biochemical recurrence (BCR) after radical prostatectomy (RP). It is unclear whether this is due to technical challenges related to operating on obese men or other biologic factors.
To examine whether obesity predicts higher prostate-specific antigen (PSA) nadir (as a measure of residual PSA-producing tissue) after RP and if this accounts for the greater BCR risk in obese men.
A retrospective analysis of 1038 RP patients from 2001 to 2010 in the multicenter US Veterans Administration-based Shared Equal Access Regional Cancer Hospital database with median follow-up of 41 mo.
All patients underwent RP. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We evaluated the relationship between body mass index (BMI) and ultrasensitive PSA nadir within 6 mo after RP. Adjusted proportional hazards models were used to examine the association between BMI and BCR with and without PSA nadir.
Mean BMI was 28.5kg/m(2). Higher BMI was associated with higher PSA nadir on both univariable (p=0.001) and multivariable analyses (p<0.001). Increased BMI was associated with increased BCR risk (hazard ratio [HR]: 1.06; p=0.007). Adjusting for PSA nadir slightly attenuated, but did not eliminate, this association (HR: 1.04, p=0.043). When stratified by PSA nadir, obesity only significantly predicted BCR in men with an undetectable nadir (p=0.006). Unfortunately, other clinically relevant end points such as metastasis or mortality were not available.
Obese men are more likely to have a higher PSA nadir, suggesting that either more advanced disease or technical issues confound an ideal operation. However, even after adjusting for the increased PSA nadir, obesity remained predictive of BCR, suggesting that tumors in obese men are growing faster. This provides further support for the idea that obesity is biologically associated with prostate cancer progression.
European urology 08/2012; 62(5):910-6. · 7.67 Impact Factor
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ABSTRACT: Findings of studies on the association between androgens and prostate cancer (PCa) are mixed. Androgens may affect prostate-specific antigen (PSA) levels, thereby influencing biopsy recommendations. Also, androgens may stimulate prostate growth at very low levels with no additional effects at higher levels (saturation model).
To test whether androgens were associated with PCa risk in the placebo arm of a prospective study in which biopsies were performed regardless of PSA level.
Of 8122 men in the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial, 4073 men (50.1%) received placebo. Key entry criteria were PSA 2.5-10 ng/ml and one prior negative biopsy.
Per-protocol biopsies at 2 and 4 yr; for-cause biopsies at physician discretion. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multivariable logistic regression was used to test the association between baseline log-transformed testosterone and dihydrotestosterone (DHT) levels and the risk of detecting either PCa or low-grade PCa (Gleason score <6) compared with high-grade PCa (Gleason score >7). In secondary analysis, we stratified the analysis by low baseline androgen levels (testosterone <10 nmol/l; DHT <0.76 nmol/l) compared with normal baseline androgen levels.
Of 4073 men, 3255 (79.9%) had at least one biopsy after randomization and were analyzed. Androgen levels tested continuously or by quintiles were generally unrelated to PCa detection or grade. PCa detection was similar among men with low compared with normal baseline testosterone levels (25.5% and 25.1%; p=0.831). In secondary analysis, higher testosterone levels at baseline were associated with higher PCa detection (odds ratio: 1.23; 95% confidence interval, 1.06-1.43; p=0.006) only if men had low baseline testosterone (<10nmol/l). For men with normal baseline testosterone (≥10 nmol/l), higher testosterone levels at baseline were unrelated to PCa risk (p=0.33). No association was found for DHT and PCa (all p>0.85).
Baseline serum testosterone and DHT levels were unrelated to PCa detection or grade. Our findings of the lowest testosterone levels being associated with the lowest PCa risk with no further changes with higher testosterone support a saturation model but must be confirmed in future studies using an a priori defined hypothesis. CLINICALTRIALS.GOV IDENTIFIER: NCT00056407.
European urology 05/2012; 62(5):757-64. · 7.67 Impact Factor
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ABSTRACT: Study Type - Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? The role of the vacuum erection device (VED) has increased with its use in combined therapy with a phosphodiesterase type 5 inhibitor (PDE5i) for penile rehabilitation after radical prostatectomy (RP) and radiotherapy. The advantages of the VED are non-invasive, cost-effective, and a possibility of preventing shrinkage of penis length. Albeit current widespread use of penile rehabilitation programmes for post-RP erectile dysfunction, independent predictors for the rehabilitation participants, as well as for its treatment success have not been fully investigated. In the present study, we have added several new predictors for rehabilitation participation, e.g. African-Americans and higher preoperative sexual function. Conversely, higher preoperative PSA concentrations and the presence of positive surgical margins were predictors for avoidance of rehabilitation. Notably, there was a primary surgeon difference, which had a trend for predicting outcome of the rehabilitation among the participants, implying their surgical technique and follow-up might influence success of the rehabilitation. OBJECTIVES: • To investigate baseline demographic and clinicopathological characteristics of men who participate in our penile rehabilitation programme after radical prostatectomy (RP). • To determine predictors for participation in rehabilitation, as well as successful rehabilitation outcome using multivariable logistic regression analyses. PATIENTS AND METHODS: • We analysed data on 2345 consecutive patients who underwent RP between 2001 and 2009 in our institution. • The decision to participate in penile rehabilitation using phosphodiesterase type 5 inhibitor (PDE5i) with a vacuum erection device (VED) was based on the patient's choice after post-RP discussions. • Rehabilitation success was defined using the following criteria: (i) patients who continued the penile rehabilitation programme and did not switch treatment from PDE5i to other erectile aids, (ii) success was noted in men who had an Expanded Prostate Cancer Index Composite (EPIC) sexual function (SF) score of >75% of the patient's baseline EPIC score, and (iii) patients who answered that they achieved adequate erections with a PDE5i. • Logistic regression analysis was used to identify factors associated with treatment participation and its success. RESULTS: • Of 676 patients, 354 (53.2%) men participated in a penile rehabilitation programme. Among 329 rehabilitation participants with available data, 96 (29.2%) had treatment success. • In multivariable regression analysis, African-Americans (odds ratio [OR] 3.47, P < 0.001), and higher preoperative SF (OR 1.02, P < 0.001) were associated with participation in rehabilitation. • Higher preoperative PSA concentration (OR 0.50, P= 0.004) and presence of positive surgical margins (OR 0.68, P= 0.042) were found to be independent predictors for non-participation in the rehabilitation. • For rehabilitation outcomes, being older at surgery (OR 0.93, P= 0.001) and adjuvant therapy (OR 0.34, P= 0.047) had a negative association with successful outcome. • There was a trend in the relationship between primary surgeon and rehabilitation success (OR 1.05, P= 0.053) CONCLUSIONS: • Those patients who have risk factors, e.g. adverse prostate cancer features, need to be carefully counselled and encouraged to participate in the penile rehabilitation programme. • Clinicians could lead patients toward successful outcomes if appropriate surgical techniques and rehabilitation are provided.
BJU International 04/2012; · 2.84 Impact Factor
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ABSTRACT: To analyze the association between prostate-specific antigen doubling time with prostate cancer risk and grade among men with prostate-specific antigen levels ≥4.0 ng/mL undergoing repeat prostate biopsy.
A total of 286 patients with prostate-specific antigen ≥4 ng/mL and available prostate-specific antigen doubling time data, who underwent repeat prostate biopsy from 1996-2009, were included in this analysis. Prostate-specific antigen doubling time was divided into three groups: >9 years, 3-9 years and <3 years. Multivariate analyses of prostate-specific antigen doubling time with cancer risk and grade (≤3 + 4 vs ≥4 + 3) were carried out using logistic regression adjusting for prebiopsy prostate-specific antigen, race, age, digital rectal examination, year of biopsy and number of prior negative biopsies.
The median prostate-specific antigen doubling time before biopsy was 4.5 years (interquartile range = 2.5-10). Shorter prostate-specific antigen doubling time was associated with higher prostate-specific antigen (P < 0.001), but it was unrelated to age, digital rectal examination or race. Shorter prostate-specific antigen doubling time as a continuous variable was associated with greater prostate cancer risk in both uni- (hazard ratio = 0.99, 95% confidence interval = 0.98-0.99, P = 0.001) and multivariate analysis (hazard ratio = 0.99, 95% confidence interval = 0.98-0.99, P = 0.004). The prevalence of cancer among prostate-specific antigen doubling time groups (>9, 3-9, <3 years) was 17%, 37% and 40%, respectively. Shorter prostate-specific antigen doubling time groups were associated with higher cancer risk (P = 0.001). Stratified by grade, short prostate-specific antigen doubling time as a continuous variable significantly predicted both low- (P = 0.010) and high-grade disease (P = 0.049). The inclusion of prostate-specific antigen doubling time groups in a multivariate model to predict biopsy positivity increased its accuracy from 0.69 to 0.74.
Prostate-specific antigen doubling time seems to provide further cancer risk assessment in men undergoing repeat biopsy for prostate-specific antigen ≥4.0 ng/mL. If validated in future studies, the present findings support the use of prostate-specific antigen doubling time in the risk stratification of this patient population.
International Journal of Urology 04/2012; 19(8):741-7. · 1.75 Impact Factor
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ABSTRACT: The impact of race and socioeconomic status (SES) in prostate cancer (CaP) outcomes has been well-studied, but controversy remains. The associations of race/SES with intermediate CaP outcomes, including positive surgical margin (PSM) and biochemical recurrence (BCR), were explored in an equal-access setting.
Data were retrospectively collected from 2502 men in the Shared Equal Access Regional Cancer Hospitals (SEARCH) database who underwent radical prostatectomy from 1989 to 2010. SES (income, education, employment, and poverty) was estimated from linkage of home ZIP code to census data. Logistic regression with adjustment for pre- and postoperative covariates estimated risk for associations between race/SES and pathologic outcomes. Cox proportional hazards models estimated risk for associations between race/SES and time to BCR.
Black men were more likely to have lower SES than white men (P < .001). On multivariate analysis, race was not associated with PSM, but higher SES was associated with less PSM and fewer Gleason sum ≥ 7 pathologic tumors when SES was assessed by education, employment, or poverty (P trend ≤ .051) and income, employment, or poverty (P trend ≤ 0.059), respectively. Crude Cox models showed black men had higher BCR risk (hazards ratio = 1.20, 95% confidence interval = 1.05-1.38, P = .009) that persisted after adjustment for covariates including SES (hazards ratio ≥ 1.18, P ≤ .040). Higher SES measured by income and poverty were associated with less BCR, but only for black men (P trend ≤ .048).
Even in an equal-access setting, higher SES predicted lower PSM risk, and race persisted in predicting BCR despite adjustment for SES. Low SES black patients may be at greatest risk for postprostatectomy BCR. Cancer 2012. © 2012 American Cancer Society.
Cancer 03/2012; 118(20):4999-5007. · 4.77 Impact Factor
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ABSTRACT: We previously found that patients undergoing robotic assisted laparoscopic radical prostatectomy vs radical retropubic prostatectomy had a higher likelihood of not being satisfied, independent of side effect profile. We hypothesized that differential preoperative expectations might contribute to this finding. In the current study we compared expectations of patients undergoing robotic assisted laparoscopic radical prostatectomy vs radical retropubic prostatectomy.
A questionnaire on expectations regarding recovery was administered to 171 patients electing to undergo robotic assisted laparoscopic radical prostatectomy or radical retropubic prostatectomy from 2008 to 2010. We prospectively collected data on patient expectations before surgery. Differences between patients undergoing robotic assisted laparoscopic radical prostatectomy vs radical retropubic prostatectomy were assessed with adjusted proportional odds models.
Patients who underwent robotic assisted laparoscopic radical prostatectomy (97) did not differ significantly from those treated with radical retropubic prostatectomy (74) in age, race, income, time between survey and surgery, and prostate specific antigen (p ≥0.4). Patients who underwent radical retropubic prostatectomy had significantly higher clinical stage and Gleason grade disease (p ≤0.007). After adjusting for socioeconomic factors, clinical stage and grade on multivariate analysis, patients who underwent robotic assisted laparoscopic radical prostatectomy expected a significantly shorter length of stay (OR 0.07, p <0.001) and earlier return to physical activity (OR 0.36, p = 0.005). The choice of robotic assisted laparoscopic radical prostatectomy (OR 0.41, p = 0.012), younger age (OR 0.49, p = 0.001) and higher preoperative International Index of Erectile Function-5-item version score (OR 0.60, p = 0.017) were independently associated with the expectation of earlier return of erections but not of continence on multivariate analysis.
The body of evidence surrounding robotic assisted laparoscopic radical prostatectomy supports shorter hospitalization but there is no conclusive evidence that the robotic approach results in earlier return to physical activity or improved disease specific outcomes. Nonetheless we found that patients who underwent robotic assisted laparoscopic radical prostatectomy had higher expectations regarding these outcomes, particularly that of erectile function recovery, than did their radical retropubic prostatectomy counterparts.
The Journal of urology 03/2012; 187(3):894-8. · 4.02 Impact Factor
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ABSTRACT: Coronary artery disease (CAD) and prostate cancer (PCa) are not only common diseases, but share many risk factors. To date, only a few studies have explored the relationship between CAD and PCa risk, with conflicting results.
The four-year REDUCE study tested dutasteride 0.5 mg daily for PCa risk reduction in men with prostate specific antigen (PSA) of 2.5 to 10.0 ng/mL and a negative biopsy. Among men who underwent at least one on-study biopsy (n = 6,729; 82.8%), the association between CAD and overall PCa risk and disease grade was examined with logistic and multinomial logistic regression adjusting for clinicopathologic features, respectively.
Overall, 547 men (8.6%) had a history of CAD. Men with CAD were significantly older and had higher body mass index, PSA, and larger prostate volumes and were more likely to have diabetes, hypertension, and hypercholesterolemia and take aspirin and statins. On multivariate analysis, CAD was associated with a 35% increased risk of PCa diagnosis (OR = 1.35, 95% CI: 1.08-1.67, P = 0.007), while elevating risk of both low- (OR = 1.34, 95% CI: 1.05-1.73, P = 0.02) and high-grade disease (OR = 1.34, 95% CI: 0.95-1.88, P = 0.09).
In a post hoc hypothesis developing secondary analysis of the REDUCE study, CAD was significantly associated with increased PCa diagnosis.
If confirmed in other studies, this suggests CAD may be a novel PCa risk factor and suggests common shared etiologies. Whether lifestyle changes shown to reduce CAD risk (i.e., weight loss, exercise, cholesterol reduction, etc.) can reduce PCa risk, warrants further study.
Cancer Epidemiology Biomarkers & Prevention 02/2012; 21(4):576-81. · 4.12 Impact Factor
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Adriana C Vidal,
Delores J Grant,
Christina D Williams,
Elizabeth Masko,
Emma H Allott,
Kathryn Shuler,
Megan McPhail,
Alexis Gaines,
Elizabeth Calloway, Leah Gerber,
Jen-Tsan Chi,
Stephen J Freedland,
Cathrine Hoyo
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ABSTRACT: Prostate cancer (PC) is the second leading cause of cancer death in men. Recent reports suggest that excess of nutrients involved in the one-carbon metabolism pathway increases PC risk; however, empirical data are lacking. Veteran American men (272 controls and 144 PC cases) who attended the Durham Veteran American Medical Center between 2004-2009 were enrolled into a case-control study. Intake of folate, vitamin B12, B6, and methionine were measured using a food frequency questionnaire. Regression models were used to evaluate the association among one-carbon cycle nutrients, MTHFR genetic variants, and prostate cancer. Higher dietary methionine intake was associated with PC risk (OR = 2.1; 95%CI 1.1-3.9) The risk was most pronounced in men with Gleason sum <7 (OR = 2.75; 95%CI 1.32- 5.73). The association of higher methionine intake and PC risk was only apparent in men who carried at least one MTHFR A1298C allele (OR = 6.7; 95%CI = 1.6-27.8), compared to MTHFR A1298A noncarrier men (OR = 0.9; 95%CI = 0.24-3.92) (p-interaction = 0.045). There was no evidence for associations between B vitamins (folate, B12, and B6) and PC risk. Our results suggest that carrying the MTHFR A1298C variants modifies the association between high methionine intake and PC risk. Larger studies are required to validate these findings.
Journal of Cancer Epidemiology 01/2012; 2012:957467.
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Christina D Williams,
Brian M Whitley,
Cathrine Hoyo,
Delores J Grant,
Gary G Schwartz,
Joseph C Presti,
Jared D Iraggi,
Kathryn A Newman, Leah Gerber,
Loretta A Taylor,
Madeline G McKeever,
Stephen J Freedland
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ABSTRACT: The objective of this study was to examine the association between calcium intake and prostate cancer risk. We hypothesized that calcium intake would be positively associated with lower risk for prostate cancer.
We used data from a case-control study conducted among veterans between 2007 and 2010 at the Durham Veterans Affairs Medical Center. The study consisted of 108 biopsy-positive prostate cancer cases, 161 biopsy-negative controls, and 237 healthy controls. We also determined whether these associations differed for blacks and whites or for low-grade (Gleason score <7) and high-grade prostate cancer (Gleason score ≥7). We administered the Harvard food frequency questionnaire to assess diet and estimate calcium intake. We used logistic regression models to obtain odds ratios (ORs) and 95% confidence intervals (CIs).
Intake of calcium from food was inversely related to risk for prostate cancer among all races in a comparison of cases and biopsy-negative controls (P = .05) and cases and healthy controls (P = .02). Total calcium was associated with lower prostate cancer risk among black men but not among white men in analyses of healthy controls. The highest tertile of calcium from food was associated with lower risk for high-grade prostate cancer in a comparison of high-grade cases and biopsy-negative controls (OR, 0.37; 95% CI, 0.15-0.90) and high-grade cases and healthy controls (OR, 0.38; 95% CI, 0.17-0.86).
Calcium from food is associated with lower risk for prostate cancer, particularly among black men, and lower risk for high-grade prostate cancer among all men.
Preventing chronic disease 01/2012; 9:E39. · 1.82 Impact Factor
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ABSTRACT: To what degree the associations between PCa risk and family history of prostate cancer (PCa) and/or breast cancer (BCa) are attributable to screening biases is unclear. We examined these questions within the REDUCE study, where biopsies were largely independent of prostate specific antigen (PSA) minimizing screening biases.
Data were from REDUCE, which tested dutasteride 0.5 mg daily for PCa risk reduction in men with PSA 2.5-10.0 ng mL(-1) and a negative prestudy biopsy. Among men undergoing at least one on-study biopsy with complete data (n = 6415; 78.1%), the association between family history and PCa risk was tested using multivariate logistic regression adjusting for clinicodemographic characteristics.
A family history of PCa alone was associated with increased PCa diagnosis (OR: 1.47, 95%CI: 1.22-1.77). In North America, PCa family history was not related to PCa diagnosis (OR: 1.02, 95%CI: 0.73-1.44), whereas outside North America, PCa family history was significantly related to diagnosis (OR: 1.72, 95%CI: 1.38-2.15) (P-interaction = 0.01). A family history of both PCa and BCa (OR: 2.54, 95%CI: 1.72-3.75) but not BCa alone (OR: 1.04, 95%CI: 0.84-1.29) was associated with increased PCa risk versus no family history and irrespective of geographical region.
In REDUCE, PCa family history was significantly related to PCa diagnosis, although only for men outside North America. The presence of both PCa and BCa family history significantly increased risk versus PCa family history alone, irrespective of geographical region. Ultimately, our observations may support the need for changes in how we address family history in terms of both risk of PCa diagnosis and general risk stratification.
Journal of Internal Medicine 12/2011; 272(1):85-92. · 5.48 Impact Factor
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ABSTRACT: Erectile dysfunction (ED) is related to several co-morbidities including obesity, metabolic syndrome, cigarette smoking, and low testosterone, all of which have been reported to be associated with adverse prostate cancer features.
To examine whether preoperative ED has a relationship with adverse prostate cancer features in patients who underwent radical prostatectomy (RP).
We analyzed data from our institution on 676 patients who underwent RP between 2001 and 2010. Crude and adjusted logistic regression models were used to investigate the association between preoperative ED and several pathological parameters. The log-rank test and multivariate proportional hazards model were conducted to determine the association of preoperative ED with biochemical recurrence (BCR).
The expanded prostate cancer index composite (EPIC) instrument was used to evaluate preoperative erectile function (EF). Preoperative normal EF was defined as EPIC-SF ≥ 60 points while ED was defined as preoperative EPIC-SF lower than 60 points.
Preoperatively, a total of 343 (50.7%) men had normal EF and 333 (49.3%) men had ED. After adjusting for covariates, preoperative ED was identified a risk factor for positive extracapsular extension (OR 1.57; P = 0.029) and high percentage of tumor involvement (OR 1.56; P = 0.047). In a Kaplan-Meier curve, a trend was identified that patients with ED had higher incidence of BCR than men with normal EF (P = 0.091). Moreover, using a multivariate Cox model, higher preoperative EF was negatively associated with BCR (HR 0.99; P = 0.014).
These results suggest that the likelihood for adverse pathological outcomes as well as BCR following prostatectomy is higher among men with preoperative ED, though these results require validation in larger datasets. The present study indicates that preoperative ED might be a surrogate for adverse prostate cancer outcomes following RP.
Journal of Sexual Medicine 12/2011; 9(4):1174-81. · 3.55 Impact Factor
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Masaki Kimura,
Lionel L Bañez,
Florian R Schroeck, Leah Gerber,
Jim Qi,
Takefumi Satoh,
Shiro Baba,
Cary N Robertson,
Philip J Walther,
Craig F Donatucci,
Judd W Moul,
Thomas J Polascik
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ABSTRACT: The association between early and late phase sexual health-related quality of life (HRQoL) following radical prostatectomy (RP) is unclear. Moreover, factors that predict either early or late sexual HRQoL decline have not been fully investigated.
The aim of this study was to evaluate the correlation between early and late phase sexual HRQoL decline, and identify clinical parameters that predict substantial sexual HRQoL decline after surgery in the early phase (3 months) and late phase (20 months) following RP.
We analyzed data on 2,345 consecutive patients who underwent radical retropubic prostatectomy, radical perineal prostatectomy, or robotic-assisted laparoscopic prostatectomy between 2001 and 2009 from the Duke Prostate Center database.
Sexual HRQoL was assessed using the Expanded Prostate Cancer Index Composite instrument at baseline, early and late phase after surgery. The Spearman rank test was used to calculate correlation coefficients between early and late phase sexual HRQoL decline. Logistic regression analysis was performed to identify factors associated with substantial sexual HRQoL decline during both phases.
Of 406 men who met our criteria, 217 (53.5%) men had normal erectile function, whereas 189 (46.5%) men had erectile dysfunction at baseline. Declines of sexual HRQoL during early phase had a significant association with that of a decline during late phase (r = 0.48, P < 0.001). In logistic regression, older age at surgery (odds ratio [OR], 1.06; P = 0.007 and OR, 1.08; P = 0.001), African-American race (OR, 4.32; P = 0.001 and OR, 3.13; P = 0.017), and overall comorbidity (OR, 1.43; P = 0.072 and OR, 1.72; P = 0.010) were consistently associated with substantial decline of sexual HRQoL in both early and late phases.
Sexual HRQoL at early and late phases after RP were strongly correlated. Additionally, several factors were identified to be a predictor for decline of sexual HRQoL. Our findings may be used to advise patients who possess aforementioned risk factors during both phases.
Journal of Sexual Medicine 07/2011; 8(10):2935-43. · 3.55 Impact Factor
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ABSTRACT: To analyze the association of diabetes mellitus (DM) with risk of prostate cancer and cancer grade among men undergoing prostate biopsy and to analyze how obesity and race modify these associations.
Retrospective analysis of 998 men from the Durham VA undergoing first prostate biopsy between 2001 and 2009 with complete data available. History of DM was determined by chart review. Patients' characteristics at biopsy were analyzed with chi-square and ranksum. Multivariable analyses of DM and risk of cancer and cancer grade were done using logistic regression adjusting for PSA, body mass index, race, age, year, and digital rectal exam.
At biopsy, 284 (28%) men had DM. DM was associated with African American (AAM; p = 0.010) and higher BMI (p < 0.001). DM was not associated with prostate cancer risk on either bivariate (p = 0.600) or multivariate analysis (p = 0.485). Similar results were found after stratification by race and obesity. In multivariable analysis, DM was associated with greater risk of high-grade disease (RR = 2.13, p = 0.024). The association was stronger among obese men (RR = 3.84, p = 0.020) and null in non-obese subjects (RR = 1.39, p = 0.460). After further stratification by race, DM was associated with high-grade disease only in obese Caucasian men (CM; RR = 5.81, p = 0.025) but not in obese AAM. DM was not associated with risk of low-grade disease in all men together or after stratification by obesity or race.
History of DM was associated with greater risk of high-grade disease. The association was strongest among obese CM suggesting the effect of DM on high-grade prostate cancer is modified by race and obesity.
Cancer Causes and Control 07/2011; 22(7):977-83. · 2.88 Impact Factor
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ABSTRACT: Experimental studies suggest omega-3 (n-3) polyunsaturated fatty acids (PUFA) suppress and n-6 PUFA promote prostate tumor carcinogenesis. Epidemiologic evidence remains inconclusive. The objectives of this study were to examine the association between n-3 and n-6 PUFA and prostate cancer risk and determine if these associations differ by race or disease aggressiveness. We hypothesize that high intakes of n-3 and n-6 PUFA will be associated with lower and higher prostate cancer risk, respectively. A case-control study comprising 79 prostate cancer cases and 187 controls was conducted at the Durham VA Medical Center. Diet was assessed using a food frequency questionnaire. Logistic regression analyses were used to obtain odds ratios (ORs) and 95% confidence intervals (95% CI) for the associations between n-3 and n-6 PUFA intakes, the dietary ratio of n-6/n-3 fatty acids, and prostate cancer risk. Our results showed no significant associations between specific n-3 or n-6 PUFA intakes and prostate cancer risk. The highest dietary ratio of n-6/n-3 was significantly associated with elevated risk of high-grade (OR, 3.55; 95% CI, 1.18-10.69; P(trend) = 0.03), but not low-grade prostate cancer (OR, 0.95; 95% CI, 0.43-2.17). In race-specific analyses, an increasing dietary ratio of n-6/n-3 fatty acids correlated with higher prostate cancer risk among white men (P(trend) = 0.05), but not black men. In conclusion, our findings suggest that a high dietary ratio of n-6/n-3 fatty acids may increase the risk of overall prostate cancer among white men and possibly increase the risk of high-grade prostate cancer among all men.
Nutrition research (New York, N.Y.) 01/2011; 31(1):1-8. · 1.20 Impact Factor
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European urology 03/2010; 58(1):8-9. · 7.67 Impact Factor
