Reduced Risk Of Prostate Cancer Research Articles

Economic Analysis: Randomized, Placebo-Controlled Clinical Trial of Dutasteride in Men at High Risk for Prostate Cancer

Objective: Given the economic burden of prostate cancer (PCa), a PCa risk-reduction medication would be desirable. A within-trial economic analysis of the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) study was performed. Methods: REDUCE, a 4-year, randomized, double-blind, placebo-controlled, parallel-group clinical trial, compared efficacy and safety of dutasteride 0.5 mg daily and placebo to reduce the risk of PCa in men at increased risk. Resource use was prospectively collected; costs from standard costing sources were applied. Utilities were obtained from published literature. Relative risks and Wilcoxon rank sums were used to examine differences between treatments. Results: Placebo patients were at significantly higher risk (P < 0.05) for concomitant medication use; and health care visits related to surgical procedures, unscheduled biopsies, acute urinary retention, urinary tract infections, or macroscopic hematuria. Total costs were significantly lower (P < 0.001) in dutasteride patients ($1 300; 95% confidence interval: $806, $1 795). Incremental cost per quality-adjusted life-year (QALY) was $26 516; cost per PCa case avoided was $19. Conclusions: During the 4-year trial period, men at increased risk for PCa receiving dutasteride incurred fewer health care costs than men receiving placebo, which helped offset dutasteride costs. Dutasteride was good value for money.

Prostate cancer and inflammation: the evidence

Chronic inflammation is now known to contribute to several forms of human cancer, with an estimated 20% of adult cancers attributable to chronic inflammatory conditions caused by infectious agents, chronic non-infectious inflammatory diseases and/or other environmental factors. Indeed, chronic inflammation is now regarded as an 'enabling characteristic' of human cancer. The aim of this review is to summarize the current literature on the evidence for a role for chronic inflammation in prostate cancer aetiology, with a specific focus on recent advances regarding the following: (i) potential stimuli for prostatic inflammation; (ii) prostate cancer immunobiology; (iii) inflammatory pathways and cytokines in prostate cancer risk and development; (iv) proliferative inflammatory atrophy (PIA) as a risk factor lesion to prostate cancer development; and (v) the role of nutritional or other anti-inflammatory compounds in reducing prostate cancer risk.

An interaction between carotene‐15,15′‐monooxygenase expression and consumption of a tomato or lycopene‐containing diet impacts serum and testicular testosterone

Lycopene, the red pigment of tomatoes, is hypothesized to reduce prostate cancer risk, a disease strongly dependent upon testosterone. In this study, mice lacking the expression of carotene-15,15'-monooxygenase (CMO-I(-/-) ) or wild-type mice were fed either a 10% tomato powder (TP), lycopene-containing (248 nmol/g diet) or their respective control diets for 4 days, after which serum testosterone was measured. A significant diet × genotype interaction (p = 0.02) suggests that the TP reduces serum testosterone concentrations in CMO-I(-/-) mice but not in wild-type mice. Similarly, testicular testosterone was lowered in TP-fed CMO-I(-/-) mice (p = 0.01), suggesting that testosterone synthesis may be inhibited in this group. A similar pattern was also observed for lycopene fed mice. Interestingly, the CMO-I(-/-) mice showed a greater expression of the gene encoding the CMO-II enzyme responsible for eccentric oxidative carotenoid cleavage in the testes. Therefore, we hypothesize that serum testosterone is reduced by lycopene metabolic products of oxidative cleavage by CMO-II in the testes. Overall, these findings suggest that genetic polymorphisms impacting CMO-I expression and its interaction with CMO-II, coupled with variations in dietary lycopene, may modulate testosterone synthesis and serum concentrations. Furthermore, carefully controlled studies with tomato products and lycopene in genetically defined murine models may elucidate important diet × genetic interactions that may impact prostate cancer risk.

Consumption of high ω-3 fatty acid diet suppressed prostate tumorigenesis in C3(1) Tag mice

Prostate cancer incidence and mortality are high in the Western world and high ω-6/ω-3 PUFA in the Western diet may be a contributing factor. We investigated whether changing from a diet that approximates ω-6 fat content of the Western diet to a high ω-3 fat diet at adulthood might reduce prostate cancer risk. Female SV 129 mice that had consumed a high ω-6 diet containing corn oil for 2 weeks were bred with homozygous C3(1)Tag transgenic male mice. All male offspring were weaned to the corn oil diet (CO) until postpuberty when half of the male offspring were transferred to a high ω-3 diet containing canola oil and fish oil concentrate (FS). High ω-3 diet increased ω-3 and decreased ω-6 fat content of mice tissues. Average weights of prostate and genitourinary bloc were significantly lower in mice consuming high ω-3 diet at adulthood (CO-FS) than mice fed a lifetime high ω-6 diet (CO–CO). There was slower progression of tumorigenesis in dorsalateral prostate of CO-FS than in CO–CO mice. CO-FS mice had slightly lower plasma testosterone level at 24 and 40 weeks, significantly lower estradiol level at 40 weeks and significantly less expressed androgen receptor (AR) in the dorsalateral prostate at 40 weeks than CO–CO mice. Consumption of high ω-3 diet lowered the expression of genes expected to increase proliferation and decrease apoptosis in dorsalateral prostate. Our results suggest that consumption of high ω-3 diet slows down prostate tumorigenesis by lowering estradiol, testosterone and AR levels, promoting apoptosis and suppressing cell proliferation in C3(1)Tag mice.

Mouse Prostate Proteome Changes Induced by Oral Pentagalloylglucose Treatment Suggest Targets for Cancer Chemoprevention

Recent in vitro and in vivo preclinical studies have suggested that the Oriental herbal compound penta-1, 2, 3, 4, 6-O-galloyl-beta-D-glucose (PGG) is a promising chemopreventive agent for prostate cancer. Little is known of its safety for chronic chemoprevention use and virtually nothing is known of its in vivo responsive proteins in the target organ. Here we treated male C57BL/6 mice with daily oral administration of PGG at two dosages (1 and 2 mg per mouse) from 7 to 14 weeks of age and profiled proteomic patterns in the prostate with iTRAQ labeling and 2D LC-MS/MS analyses. While neither dose affected feed intake and body weight gain, the 2 mg dose (∼80-100 mg per kg) led to a minor but statistically significant decrease of the weight of prostate and thymus. For proteomic profiling, five prostates were pooled from each group for protein extraction. Proteins were denatured, reduced, alkylated and digested to peptides. The peptides were labeled with iTRAQ reagents, mixed and subjected to 2D LC-MS/MS analyses. PGG consumption suppressed the abundance of oncoproteins (e.g., fatty acid synthase, clusterin) and up-regulated that of tumor suppressor proteins (e.g., glutathione S-transferase M), signifying changes that may contribute to prostate cancer risk reduction.

Dutasteride Reduces Prostatitis Symptoms Compared With Placebo in Men Enrolled in the REDUCE Study

Men at risk for prostate cancer may concurrently experience chronic prostatitis or pelvic pain. We evaluated the effect of dutasteride on prostatitis-like symptoms in the REDUCE study population. REDUCE was a 4-year, randomized, double-blind, placebo controlled study of prostate cancer risk reduction with 0.5 mg dutasteride vs placebo in men 50 to 75 years old with prostate specific antigen 2.5 to 10 ng/ml and a negative prostate biopsy in the previous 6 months. In this analysis we investigated change from baseline in Chronic Prostatitis Symptom Index in men with prostatitis-like pain (Chronic Prostatitis Symptom Index pain subscore 5 or greater) and prostatitis-like syndrome (perineal or ejaculatory pain plus Chronic Prostatitis Symptom Index pain subscore 4 or greater), the proportion of subjects with at least a moderate Chronic Prostatitis Symptom Index response (6-unit or greater improvement) and reports of new onset clinical prostatitis. Of 5,379 men with a total baseline Chronic Prostatitis Symptom Index score 678 (12.6%) had prostatitis-like pain and 427 (7.9%) had prostatitis-like syndrome. Chronic Prostatitis Symptom Index total score decreased significantly at 48 months in the dutasteride group vs placebo in men with prostatitis-like pain (p <0.0001) and with prostatitis-like syndrome (t test p = 0.03). There were significantly more Chronic Prostatitis Symptom Index responders with dutasteride vs placebo in the prostatitis-like pain (49% vs 37%, respectively, p = 0.0033) and prostatitis-like syndrome (46% vs 35%, Fisher's exact test p = 0.0265) subgroups. Prostatitis was reported as an adverse event by significantly more men randomized to placebo (3.6%) than to dutasteride (2.5%, p = 0.003). Long-term dutasteride therapy resulted in improvement in prostatitis related symptoms in older men with an increased prostate specific antigen.

Prevalence and Correlates of Vitamin and Supplement Usage Among Men With a Family History of Prostate Cancer

Men who have a brother with prostate cancer have a 2-fold increased risk of being diagnosed with prostate cancer. Strategies employed by these men to reduce prostate cancer risk are not well understood. Preliminary studies have shown that men with a family history of prostate cancer have a high rate of vitamin and supplement usage aimed at the prevention of prostate cancer. The authors analyzed data from a cross-sectional study of men with familial and hereditary prostate cancer and their unaffected brothers. A total of 542 unaffected men who had at least one brother who had been diagnosed with prostate cancer regarding their use of vitamins and supplements, as well as the motivation for use, were interviewed. The associations between subject characteristics and vitamin and supplement use were evaluated using an unconditional logistic regression modeling approach. Overall, 59.2% and 36.5% of men reported ever using and currently using, respectively, one or more vitamins or supplements (including multivitamins). One third of men took a vitamin or supplement that has been targeted for prostate health or cancer prevention, including green tea, magnesium, male hormones, saw palmetto, selenium, soy, vitamins A, C, E, and zinc. Increasing age at time of survey was associated with vitamin/supplement use (odds ratio [OR] = 1.03; 95% confidence interval [CI] = 1.01-1.05). After adjusting for age at time of survey, being younger than an affected brother was associated with vitamin and supplement use (OR = 1.51; 95% CI = 1.01-2.25). A total of 25% of men reported obtaining information from books or articles as the most common source of information. The findings indicate that men at an increased risk for prostate cancer report a high rate of vitamin and supplement use, including supplements targeted for prostate cancer prevention. Men with a family history of prostate cancer represent a target population for future chemopreventative agents.

Dutasteride Improves Outcomes of Benign Prostatic Hyperplasia When Evaluated for Prostate Cancer Risk Reduction: Secondary Analysis of the REduction by Dutasteride of Prostate Cancer Events (REDUCE) Trial

To investigate the effect of dutasteride versus placebo on the symptoms and associated complications of male lower urinary tract symptoms and benign prostatic hyperplasia (BPH) across a range of prostate volumes and BPH symptoms in men evaluated for prostate cancer risk reduction in the 4-year REduction by DUtasteride of prostate Cancer Events (REDUCE) trial. REDUCE was a multicenter, randomized, double-blind, placebo-controlled study of prostate cancer risk reduction with daily dutasteride 0.5 mg or placebo. Eligible men were aged 50-75 years, with a prostate-specific antigen level of 2.5-10 ng/mL and a prostate volume of ≤80 cm3. The prespecified and post hoc analyses were performed on the incidence of acute urinary retention, BPH-related surgery, and urinary tract infections, as well as on changes in prostate volume, International Prostate Symptom Score, BPH Impact Index, and maximal urinary flow rate (Qmax). A total of 8122 men were included in the efficacy population. During the 4-year study, the International Prostate Symptom Score increased in placebo-treated patients, while dutasteride-treated patients had a stabilized or decreased International Prostate Symptom Score and improved BPH Impact Index and quality of life due to urinary symptom scores across all prostate volume quintiles (including prostate glands smaller than those studied in previous dutasteride trials). 48 months, the incidence of acute urinary retention or BPH-related surgery was significantly less in the dutasteride group (2.5%) than in the placebo group (9%) overall (P<.001) and in each baseline prostate volume quintile (P<.01). During the 4-year study, dutasteride was associated with a decreased risk of BPH progression in men with mild-to-moderate symptoms and normal or enlarged prostates.

Serum estrogen levels and prostate cancer risk in the prostate cancer prevention trial: a nested case–control study

ObjectiveFinasteride reduces prostate cancer risk by blocking the conversion of testosterone to dihydrotestosterone. However, whether finasteride affects estrogens levels or change in estrogens affects prostate cancer risk is unknown.MethodsThese questions were investigated in a case–control study nested within the prostate cancer prevention trial (PCPT) with 1,798 biopsy-proven prostate cancer cases and 1,798 matched controls.ResultsAmong men on placebo, no relationship of serum estrogens with risk of prostate cancer was found. Among those on finasteride, those in the highest quartile of baseline estrogen levels had a moderately increased risk of Gleason score < 7 prostate cancer (for estrone, odds ratio [OR] = 1.51, 95% confidence interval [CI] = 1.06–2.15; for estradiol, OR = 1.50, 95% CI = 1.03–2.18). Finasteride treatment increased serum estrogen concentrations; however, these changes were not associated with prostate cancer risk.ConclusionOur findings confirm those from previous studies that there are no associations of serum estrogen with prostate cancer risk in untreated men. In addition, finasteride results in a modest increase in serum estrogen levels, which are not related to prostate cancer risk. Whether finasteride is less effective in men with high serum estrogens, or finasteride interacts with estrogen to increase cancer risk, is uncertain and warrants further investigation.

Mouse Prostate Proteomes Are Differentially Altered by Supranutritional Intake of Four Selenium Compounds

We have shown that, in contrast to selenomethionine (SeMet) or selenite, methylseleninic acid (MSeA) and Se-methylselenocysteine (MSeC) exert prostate cancer (PCa) inhibitory effect in preclinical models. Here we investigated the prostate proteome signatures of mice treated with each selenium (Se) form for hypothesis generation concerning their potential in vivo molecular targets and cancer risk modification. Nude mice bearing subcutaneous PC-3 xenografts were treated daily with each Se form (3 mg Se/kg) orally for 45 days. Five prostates were pooled from each group. Their proteomes were profiled by LC-MS/MS with iTRAQ labeling. Of the 1,088 proteins identified, 72 were significantly modulated by one or more Se forms. MSeA and MSeC each induced separate sets of tumor suppressor proteins and suppressed different onco-proteins. Proteins induced by selenite and shared with MSeC were related to energy metabolism (e.g., fatty-acid synthase), and those induced by SeMet included vimentin and heat-shock protein-70, favoring cancer growth. While proteome changes induced by MSeA were associated with PCa risk reduction, desirable risk-reducing signatures induced by MSeC were counterbalanced by risk-promoting patterns shared with selenite and SeMet. We propose that the balance of oncogenic vs. suppressor protein patterns in the prostate may impact the direction of PCa risk modification by a given selenium.

Within-Group Differences Between Native-Born and Foreign-Born Black Men on Prostate Cancer Risk Reduction and Early Detection Practices

To better address prostate cancer disparities, we investigated the differences among US-born, African-born, and Caribbean-born Black men on prostate cancer risk reduction and early detection behaviors. Data were collected from over 3,400 Black men in five cities in Florida. One-way analysis of variance was used to explore the ethnic variations among the three study groups. We found that there were significant differences among the three groups. The US-born Black men had the highest knowledge, were most likely to have health insurance, and consume the most meat compared to African-born, and Caribbean-born Black men. African-born Black men were most likely to use chemoprevention products and discuss prostate cancer risk-reduction and early detection with a physician. Given the significant number of foreign-born Blacks in the US, it is important to disaggregate the data of US-born and foreign-born Blacks to develop effective programs and policies to address the needs of each group.

Abstract 1816: Effects of high ω-3 fatty acid diet on prostate tumorigenesis in C3(1) Tag mice

Abstract Epidemiological studies have shown that intake of diet high in omega 6 polyunsaturated fatty acid (ω-6 PUFA) increases the risk of prostate cancer while the diet high in omega-3 polyunsaturated fatty acid (ω-3 PUFA) decreases the risk. Omega-6 PUFA are abundant in corn oil and sunflower oil while omega-3 PUFA are abundant in fish oil, canola oil and walnut. Both ω-6 and ω-3 play an important role in prostate cancer risk. Prostate cancer incidence and mortality are high in the Western world and high ω-6/ ω-3 PUFA in the Western diet may be a contributing factor. The aim of this study was to investigate whether a change from a diet that approximates the ω-6 fatty acid content of the Western diet to a high ω-3 fatty acid diet at adulthood might reduce prostate cancer risk. Female SV 129 mice that had consumed a high ω-6 diet containing 10% w/w corn oil (containing 50% ω-6 and 1% ω-3) for two weeks were bred with homozygous C3(1) Tag transgenic male mice. All male offspring (hemizygous) were weaned to the corn oil diet and consumed this diet until post puberty (7 weeks). Since the aim of the study was to simulate a diet change at adulthood, half of the male offspring were transferred to a high ω-3 diet containing 5%w/w canola oil and 5% w/w fish oil concentrate (containing 1%w/w ω-6 and 35%w/w ω-3). The male hemizygous mice were euthanized at age 24wks and 40wks (end of reproduction). Gas chromatography was used to assess the fatty acid composition in the prostate, liver and fat tissues. Enzyme-linked immunoassay was used to assess the levels of testosterone and estradiol in blood plasma. RT2 PCR and WB analyses were used to assess mRNA gene and protein expression respectively in the dorsalateral (DL) prostate. The results demonstrated that high ω-3 diet increased the ALA, EPA and DHA and decreased the LA and AA content of the prostate, liver and fat tissues. The average weights of prostate and genitourinary bloc (GU block) at 24 wks and 40 wks were significantly lower in mice that consumed the high ω-3 diet at adulthood (CO-FS) than in mice that consumed the high ω-6 diet (CO-CO) throughout life. Compared to mice in CO-CO group, CO-FS mice had lower plasma testosterone level at 24wks and 40wks, and significantly lower estradiol level at 40wks. Gene expression analyses showed that consumption of high ω-3 diet altered expression of genes that would be expected to slow proliferation and increase apoptosis in the DL prostate. Our findings suggest that if adult consume high ω-3 (but low in ω-6) diet, it may be useful in the suppression and prevention of prostate cancer. Further ongoing investigation include pathological evaluation of DL prostate from the two diet groups and immunohistochemical analyses to assess the expression of AR, ER and proliferation in the mice DL prostate. TUNEL assay will be used to assess apoptosis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1816. doi:10.1158/1538-7445.AM2011-1816

Plasma Coenzyme Q10 Levels and Prostate Cancer Risk: The Multiethnic Cohort Study

Coenzyme Q10 (CoQ10) is considered to be a potential anticancer agent, but epidemiologic evidence regarding CoQ10 and prostate cancer risk is lacking. We examined the association of circulating CoQ10 levels with prostate cancer risk, using prediagnostic blood samples. Each of the 307 cases was individually matched to approximately 2 controls, for a total of 596 controls, on age, ethnicity, geographic location, date/time of specimen collection, and hours of fasting. Logistic regression was used to compute ORs and 95% CIs. There was no overall statistically significant association of plasma CoQ10 levels with prostate cancer risk (P(trend) = 0.50). However, after matched sets in which controls who had possible undiagnosed prostate cancer (prostate specific antigen value >4.0) were excluded, the ORs for quintiles 2 to 5 were all less than 1.0. The results suggest the possibility that moderate levels of circulating CoQ10 may be optimal for the reduction of prostate cancer risk; however, the findings were weak and not statistically significant. Because this is the first epidemiologic study of the association between CoQ10 and prostate cancer, further research on this topic is needed. If a nutritional factor such as CoQ10 were determined to reduce prostate cancer risk, it would have considerable public health significance because of the very high incidence of this cancer.

Serum lycopene concentration and prostate cancer risk: results from the Prostate Cancer Prevention Trial.

Lycopene has been promoted for prostate cancer prevention, despite the inconsistency of scientific evidence. This nested case-control study examined whether serum lycopene was associated with prostate cancer risk among participants in the Prostate Cancer Prevention Trial, a placebo-controlled trial of finasteride for prostate cancer prevention. Presence or absence of cancer was determined by prostate biopsy, recommended during the trial due to elevated prostate specific antigen (PSA) level or abnormal digital rectal examination (DRE) and offered to all men at the trial end. There were 1,683 cases (461 Gleason score ≥ 7, 125 Gleason score ≥ 8) and 1,751 controls. There were no associations of lycopene with prostate cancer risk. The odds ratios for a linear increase in lycopene (per 10 μg/dL) were 0.99 (95% CI: 0.94-1.04), 1.01 (0.94-1.08), and 1.02 (0.90-1.15) for Gleason 2 to 6, 7 to 10, and 8 to 10, respectively. In the placebo arm, a 10 μg/dL increase in lycopene was associated with a 7% (95% CI: 14-0) reduced risk of cancer diagnosed following an elevated PSA or abnormal DRE, which are cancers that best match those detected in screened populations. However, a 10 μg/dL increase in lycopene was also associated with an 8% (95% CI: 1-16) increased risk of cancer diagnosed without a biopsy prompt, which are cancers generally not detected. These findings were similar for low- and high-grade cancer. This study does not support a role for lycopene in prostate cancer prevention. Scientists and the public should understand that early studies supporting an association of dietary lycopene with reduced prostate cancer risk have not been replicated in studies using serum biomarkers of lycopene intake. Recommendations of professional societies to the public should be modified to reflect the likelihood that increasing lycopene intake will not affect prostate cancer risk.

Biopsy Misidentification Identified by DNA Profiling in a Large Multicenter Trial

The Reduction by Dutasteride of Prostate Cancer Events (REDUCE) prostate cancer risk reduction study randomly assigned 8,231 men to dutasteride or placebo for 4 years. Protocol-mandated biopsies were obtained after 2 and 4 years. After the discovery of three cases of biopsy sample misidentification in the first 2 years, all protocol-mandated biopsy samples were DNA tested to verify biopsy identity. Biopsy and blood DNA profiling was performed retrospectively for the year 2 scheduled biopsies and prospectively for the year 4 scheduled biopsies. Toward the end of year 2, multiple changes were made to improve sample handling and chain of custody. Of the 6,458 year 2 and 4,777 year 4 biopsies, 26 biopsies reflecting 13 sample handling errors at year 2 (0.4%) and one biopsy reflecting one sample handling error at year 4 (0.02%) were confirmed to be mismatched to the patient for whom they were originally submitted. Of 6,733 reference blood samples profiled, 31 (0.5%) were found to be mismatched to the patient's verified identity profile. Sample identification errors occurred at local research sites and central laboratories. Biopsy misidentification is a potential problem in clinical laboratories and clinical trials. Until now, biopsy misidentification has not been studied in the setting of a large, multinational clinical trial. In the REDUCE study, process improvement initiatives halfway through the trial dramatically reduced biopsy mismatches. The potential for biopsy mismatches in clinical trials and clinical practice is an under-recognized problem that requires rigorous attention to details of chain of custody and consideration of more widespread DNA identity testing.

334 STATIN USE OF THE RISK OF PROSTATE CANCER AND HIGH-GRADE PROSTATE CANCER: RESULTS FROM THE REDUCE STUDY

INTRODUCTION AND OBJECTIVES: Prior studies suggest statins are associated with lower PSA levels. As PSA is the primary method for prostate cancer screening, this may confound any associations between statins and prostate cancer risk. We examined the association between statins and cancer and high-grade cancer risk in the REDUCE study, where biopsies were largely independent of PSA. METHODS: The 4-year REDUCE study tested dutasteride 0.5 mg daily for prostate cancer risk reduction in men with PSA of 2.5–10.0 ng/mL and a negative biopsy. Among men who underwent at least one on-study biopsy (n 6,729; 82.8%), the association between baseline statin use and risk of high-grade (Gleason 7) or low-grade prostate cancer (Gleason 7) vs. no cancer was examined using multinomial logistic regression adjusting for age, race, baseline PSA, prostate volume, rectal examination findings and body mass index. RESULTS: Overall, 1,174 men (17.5%) were on a statin at baseline. Men taking statins were older, had lower PSA levels, higher BMI values, and lower serum testosterone and dihydrotestosterone levels. Statin use was not associated with lowor high-grade cancer risk on crude analysis. On multivariate analyses, statin use remained not significantly related to low-grade (RRR 1.05, 95%CI 0.87–1.27, p 0.62) or high-grade cancer (RRR 1.14, 95%CI 0.87–1.49, p 0.34). CONCLUSIONS: Among men with a negative baseline biopsy and follow-up biopsies that were independent of PSA, statins were not related to cancer or high-grade cancer. These findings do not support a role for statins in primary prostate cancer prevention.

CASP8 promoter polymorphism, mRNA expression and risk of prostate cancer among Chinese men

Caspase-8 (CASP8) plays a key role in apoptosis. We examined by genotyping whether the −652 six-nucleotide insertion-deletion (6N ins/del) polymorphism in the CASP8 promoter region was associated with prostate cancer risk in a hospital-based case-control study of 406 Chinese prostate cancer patients and 408 age-matched cancerfree controls. Additionally, 23 prostate cancer tissues were analyzed for CASP8 mRNA expression. We found a significantly decreased prostate cancer risk for the 6N ins/del genotype [adjusted odds ratio ( OR)=0.68; 95% confidence interval ( CI)=0.51-0.92] and del/del genotype ( OR=0.34; 95% CI=0.19-0.63) compared with the ins/ins genotype. The 6N del allele was associated dose-dependently with decreased prostate cancer risk ( P trend = 0.001). RT-PCR showed that individuals with the 6N del allele had lower CASP8 mRNA levels than those with the ins/ins genotype ( P = 0.024). These findings suggested that the CASP8-652 6N ins/del polymorphism may affect the susceptibility to prostate cancer and reduce prostate cancer risk among Chinese men.

Diabetes and cancer risk in the REDUCE trial.

194 Background: Men with diabetes mellitus (DM) are less likely to be diagnosed with prostate cancer (PC). As diabetic men have lower PSA values, it is unclear if this is due to reduced PC incidence or lower biopsy rates from the lower PSA. To account for differential biopsy rates, we explored the link between DM and risk of PC and high-grade PC in the REDUCE trial. We also explored if these associations differed by body mass index (BMI) as a prior study suggested BMI may modify the effect of DM on PC aggressiveness. Methods: The 4-year REDUCE study tested the effect of dutasteride 0.5 mg daily on PC risk reduction in men with PSA of 2.5-10.0 ng/mL and a negative prostate biopsy. Men underwent study-mandated biopsies at 2 and 4 years regardless of PSA. DM was determined by self report at baseline. BMI (kg/m2) was calculated from height and weight measured at baseline. The risk of PC and high-grade PC (Gleason 7-10) was determined using multivariate logistic regression adjusting for age, race, BMI, PSA, and treatment arm. Effect modification by BMI (&lt;25, 25-29.9, and &gt;30 kg/m2) was tested via interactions. Results: Of 8,122 men in the REDUCE trial, 499 (6.1%) had DM. Diabetic men were older (63.8 vs. 62.7 yrs, p=0.001) with a higher BMI (median BMI 27.8 vs. 26.8, p&lt;0.0001). After adjusting for age and BMI, diabetic men had lower PSA values (p=0.04). On multivariate analysis, DM was not associated with PC risk (OR 0.96, 95% CI 0.75-1.22, p=0.74). When stratified by BMI, DM was not associated with PC risk in any group (all p&gt;0.23) and the results did not vary by BMI category (p-interaction=0.13). DM was not associated with high-grade PC on multivariate analysis (OR 0.88, 95% CI 0.58-1.33, p=0.55). When stratified by BMI, though DM was not associated with high-grade PC risk in any single group (all p&gt;0.14), there was a suggestion of effect modification by BMI (p-interaction=0.056) with a positive association between DM and high-grade PC in obese men (OR 1.32) and an inverse association in normal weight men (OR 0.35). Conclusions: In the REDUCE trial, when all men undergo biopsy regardless of PSA, DM is not associated with lower PC risk, but rather equal PC risk and equal risk of high-grade PC. These results suggest the lower rate of PC among diabetic men in prior studies may be driven by lower biopsy rates from lower PSA. [Table: see text]

Use of Non-Steroidal Anti-Inflammatory Drugs and Prostate Cancer Risk: A Population-Based Nested Case-Control Study

BackgroundDespite strong laboratory evidence that non-steroidal anti-inflammatory drugs (NSAIDs) could prevent prostate cancer, epidemiological studies have so far reported conflicting results. Most studies were limited by lack of information on dosage and duration of use of the different classes of NSAIDs.MethodsWe conducted a nested case-control study using data from Saskatchewan Prescription Drug Plan (SPDP) and Cancer Registry to examine the effects of dose and duration of use of five classes of NSAIDs on prostate cancer risk. Cases (N = 9,007) were men aged ≥40 years diagnosed with prostatic carcinoma between 1985 and 2000, and were matched to four controls on age and duration of SPDP membership. Detailed histories of exposure to prescription NSAIDs and other drugs were obtained from the SPDP.ResultsAny use of propionates (e.g., ibuprofen, naproxen) was associated with a modest reduction in prostate cancer risk (Odds ratio = 0.90; 95%CI 0.84-0.95), whereas use of other NSAIDs was not. In particular, we did not observe the hypothesized inverse association with aspirin use (1.01; 0.95–1.07). There was no clear evidence of dose-response or duration-response relationships for any of the examined NSAID classes.ConclusionsOur findings suggest modest benefits of at least some NSAIDs in reducing prostate cancer risk.

Corrigendum

BJU InternationalVolume 107, Issue 2 p. 344-344 Free Access Corrigendum This article corrects the following: 5-α-Reductase inhibitors for prostate cancer chemoprevention: an updated Cochrane systematic review Timothy J. Wilt, Roderick MacDonald, Karen Hagerty, Paul Schellhammer, James Tacklind, Mark R. Somerfield, Barnett S. Kramer, Volume 106Issue 10BJU International pages: 1444-1451 First Published online: October 27, 2010 First published: 05 January 2011 https://doi.org/10.1111/j.1464-410X.2010.10069.xAboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL In [1], the following errors appeared in the print issue BJU 106:10. In DISCUSSION, on PAGE 1450, middle column, third paragraph, the third and final paragraph of the section should have appeared as: “In conclusion, 5-α-RIs reduce prostate cancer risk in men who undergo regular prostate cancer screening using PSA level measurements and DRE with follow-up prostate biopsies. The impact of 5-α-RIs on absolute or relative rates of prostate cancer in men who are not being regularly screened is not clear. Effects are consistent across race, family history and age. Information is inadequate to assess the impact on mortality. Long-term compliance in randomized trials is high. Decisions to initiate chemoprevention with 5-α-RIs should incorporate this information.” This should have been published instead of the paragraph originally published. REFERENCE 1 Wilt TJ, MacDonald R, Hagerty K, Schellhammer P, Tacklind J, Somerfield MR, Kramer BS. 5-α-Reductase inhibitors for prostate cancer chemoprevention: an updated Cochrane systematic review. BJU Int 2010; 106: 1444– 51 Volume107, Issue2January 2011Pages 344-344 ReferencesRelatedInformation