Coffee consumption and risk of localized, advanced and fatal prostate cancer: a population-based prospective study.

BACKGROUND: The epidemiological evidence on possible relationships between coffee consumption and prostate cancer (PCa) risk by subtype of the disease (localized, advanced) and fatal PCa risk is limited. MATERIALS AND METHODS: A population-based cohort of 44 613 Swedish men aged 45-79 years was followed up from January 1998 through December 2010 for incidence of localized (n = 2368), advanced (n = 918) and fatal (n = 515) PCa. We assessed the associations between coffee consumption and localized, advanced and fatal PCa risk using competing-risk regressions. We examined possible effect modification by body mass index (BMI). RESULTS: For localized PCa, each one cup increase in daily coffee consumption was associated with a 3% reduced risk [sub-hazard ratio (SHR) = 0.97, 95% confidence interval (CI) = 0.95-0.99]. For advanced and fatal PCa, we found a non-significant inverse association; each one cup increase was associated with a 2% reduced risk of advanced [SHR (95% CI) = 0.98 (0.95-1.02)] and fatal PCa [SHR (95% CI) = 0.98 (0.93-1.03)]. We observed evidence of effect modification by BMI for localized PCa (Pinteraction = 0.03); the inverse association was stronger among overweight and obese men (BMI ≥ 25 kg/m(2)) compared with normal-weight men (BMI < 25 kg/m(2)). CONCLUSIONS: We observed a clear inverse association between coffee consumption and risk of localized PCa, especially among overweight and obese men.

Thoracic epidural analgesia inhibits the neuro-hormonal but not the acute inflammatory stress response after radical retropubic prostatectomy.

BACKGROUND: Epidural anaesthesia and analgesia has been shown to suppress the neuro-hormonal stress response, but its role in the inflammatory response is unclear. The primary aim was to assess whether the choice of analgesic technique influences these processes in patients undergoing radical retropubic prostatectomy. METHODS: Twenty-six patients were randomized to Group P (systemic opioid-based analgesia) or Group E (thoracic epidural-based analgesia) perioperatively. Induction and maintenance of anaesthesia followed a standardized protocol. The following measurements were made perioperatively: plasma cortisol, glucose, insulin, C-reactive proteins, leucocyte count, plasma cytokines [interleukin (IL)-6, tumour necrosis factor (TNF)-α], and pokeweed mitogen-stimulated cytokines [interferon (IFN)-γ, IL-2, IL-12p70, IL-10, IL-4, and IL-17]. Other parameters recorded were pain, morphine consumption, and perioperative complications. RESULTS: Plasma concentration of cortisol and glucose were significantly higher in Group P compared with Group E at the end of surgery, the mean difference was 232 nmol litre(-1) [95% confidence interval (CI) 84-381] (P=0.004) and 1.6 mmol litre(-1) (95% CI 0.6-2.5) (P=0.003), respectively. No significant differences were seen in IL-6 and TNF-α at 24 h (P=0.953 and 0.368, respectively) and at 72 h (P=0.931 and 0.691, respectively). IL-17 was higher in Group P compared with Group E, both at 24 h (P=0.001) and 72 h (P=0.018) after operation. Pain intensity was significantly greater in Group P compared with Group E (P<0.05) up to 24 h. CONCLUSIONS: In this small prospective randomized study, thoracic epidural analgesia reduced the early postoperative stress response but not the acute inflammatory response after radical retrobupic prostatectomy, suggesting that other pathways are involved during the acute phase reaction.

Dietary cadmium exposure and prostate cancer incidence: a population-based prospective cohort study.

BACKGROUND: Experimental data convincingly propose the toxic metal cadmium as a prostate carcinogen. Cadmium is widely dispersed into the environment and, consequently, food is contaminated. METHODS: A population-based cohort of 41 089 Swedish men aged 45-79 years was followed prospectively from 1998 through 2009 to assess the association between food frequency questionnaire-based estimates of dietary cadmium exposure (at baseline, 1998) and incidence of prostate cancer (3085 cases, of which 894 were localised and 794 advanced) and through 2008 for prostate cancer mortality (326 fatal cases). RESULTS: Mean dietary cadmium exposure was 19 µg per day±s.d. 3.7. Multivariable-adjusted dietary cadmium exposure was positively associated with overall prostate cancer, comparing extreme tertiles; rate ratio (RR) 1.13 (95% confidence interval (CI): 1.03-1.24). For subtypes of prostate cancer, the RR was 1.29 (95% CI: 1.08-1.53) for localised, 1.05 (95% CI: 0.87-1.25) for advanced, and 1.14 (95% CI: 0.86-1.51) for fatal cases. No statistically significant difference was observed in the multivariable-adjusted risk estimates between tumour subtypes (P(heterogeneity)=0.27). For localised prostate cancer, RR was 1.55 (1.16-2.08) among men with a small waist circumference and RR 1.45 (1.15, 1.83) among ever smokers. CONCLUSION: Our findings provide support that dietary cadmium exposure may have a role in prostate cancer development.

Body mass index in early and middle-late adulthood and risk of localised, advanced and fatal prostate cancer: a population-based prospective study.

BACKGROUND: The relationships between body mass index (BMI) during early and middle-late adulthood and incidence of prostate cancer (PCa) by subtype of the disease (localised, advanced) and fatal PCa is unclear. METHODS: A population-based cohort of 36,959 Swedish men aged 45-79 years was followed up from January 1998 through December 2008 for incidence of PCa (1530 localised and 554 advanced cases were diagnosed) and through December 2007 for PCa mortality (225 fatal cases). RESULTS: From a competing-risks analysis, incidence of localised PCa was observed to be inversely associated with BMI at baseline (middle-late adulthood; rate ratio (RR) for 35 kg m(-2) when compared with 22 kg m(-2) was 0.69 (95% CI 0.52-0.92)), but not at age 30. For fatal PCa, BMI at baseline was associated with a nonstatistically significant increased risk (RR for every five-unit increase: 1.12 (0.88-1.43)) and BMI at age 30 with a decreased risk (RR for every five-unit increase: 0.72 (0.51-1.01)). CONCLUSION: Our results indicate an inverse association between obesity during middle-late, but not early adulthood, and localised PCa. They also suggest a dual association between BMI and fatal PCa--a decreased risk among men who were obese during early adulthood and an increased risk among those who were obese during middle-late adulthood.

Thoracic epidural analgesia or patient-controlled local analgesia for radical retropubic prostatectomy: a randomized, double-blind study.

BACKGROUND: Postoperative pain after radical retropubic prostatectomy is moderate to severe. The primary aim of this study was to assess whether intra-abdominal local anaesthetics provide similar analgesia compared with thoracic epidural analgesia (TEA). METHODS: Fifty patients, ASA I-II, participated in this prospective, double-blinded study. All patients had TEA. After operation, they were randomized into two groups of 25 patients: Group PCLA (patient-controlled local analgesia): self-administration of 10 ml of ropivacaine 2 mg ml⁻¹ via the intra-abdominal catheter for 48 h. Group TEA: infusion of 10 ml h⁻¹ of ropivacaine 1 mg ml⁻¹, fentanyl 2 µg ml⁻¹, and epinephrine 2 µg ml⁻¹ epidurally for 48 h. The primary endpoint was pain on coughing at 4 h after operation. Rescue medication was morphine i.v. as required. RESULTS: Pain on coughing at 4, 24, and 48 h was significantly lower in Group TEA [0 (0-10)] compared with Group PCLA [4 (0-10)] (P<0.05). Significantly lower pain intensity was also found in Group TEA compared with Group PCLA at the incision site, deep pain, and pain on coughing at 4 and 24 h (P<0.05). Morphine consumption was significantly greater in Group PCLA [12 (0-46)] compared with Group TEA [0 (0-20)] at 0-48 h after operation [median (range)] (P=0.015). Maximum expiratory pressure was higher in Group TEA compared with Group PCLA at 24 h (P<0.01). CONCLUSIONS: TEA provides superior postoperative pain relief with better preservation of expiratory muscle strength compared with PCLA.

Incidence and mortality of incidental prostate cancer: a Swedish register-based study.

In a national register-based study of incidence trends and mortality of incidental prostate cancer in Sweden, we found that a significant proportion (26.6%) of affected men diagnosed died of their disease, which challenges earlier descriptions of incidental prostate cancer as a non-lethal disease.

A prospective study of lifetime physical activity and prostate cancer incidence and mortality.

BACKGROUND: The possible benefit of lifetime physical activity (PA) in reducing prostate cancer incidence and mortality is unclear. METHODS: A prospective cohort of 45,887 men aged 45-79 years was followed up from January 1998 to December 2007 for prostate cancer incidence (n=2735) and to December 2006 for its subtypes and for fatal (n=190) prostate cancer. RESULTS: We observed an inverse association between lifetime (average of age 30 and 50 years, and baseline age) total PA levels and prostate cancer risk. Multivariate-adjusted incidence in the top quartile of lifetime total PA decreased by 16% (95% confidence interval (CI)=2-27%) compared with that in the bottom quartile. We also observed an inverse association between average lifetime work or occupational activity and walking or bicycling duration and prostate cancer risk. Compared with men who mostly sit during their main work or occupation, men who sit half of the time experienced a 20% lower risk (95% CI=7-31%). The rate ratio linearly decreased by 7% (95% CI=1-12%) for total, 8% (95% CI=0-16%) for localised and 12% (95% CI=2-20%) for advanced prostate cancer for every 30 min per day increment of lifetime walking or bicycling in the range of 30 to 120 min per day. CONCLUSIONS: Our results suggest that not sitting for most of the time during work or occupational activity and walking or bicycling more than 30 min per day during adult life is associated with reduced incidence of prostate cancer.

TMPRSS2:ERG gene fusion associated with lethal prostate cancer in a watchful waiting cohort.

The identification of the TMPRSS2:ERG fusion in prostate cancer suggests that distinct molecular subtypes may define risk for disease progression. In surgical series, TMPRSS2:ERG fusion was identified in 50% of the tumors. Here, we report on a population-based cohort of men with localized prostate cancers followed by expectant (watchful waiting) therapy with 15% (17/111) TMPRSS2:ERG fusion. We identified a statistically significant association between TMPRSS2:ERG fusion and prostate cancer specific death (cumulative incidence ratio=2.7, P<0.01, 95% confidence interval=1.3-5.8). Quantitative reverse-transcription-polymerase chain reaction demonstrated high ets-related [corrected] gene (ERG) expression to be associated with TMPRSS2:ERG fusion (P<0.005). These data suggest that TMPRSS2:ERG fusion prostate cancers may have a more aggressive phenotype, possibly mediated through increased ERG expression.

Deletion polymorphism of the UGT2B17 gene is associated with increased risk for prostate cancer and correlated to gene expression in the prostate.

Metabolism of androgens includes glucuronidation, the major pathway of steroid elimination in several steroid target tissues. Glucuronidation is catalysed by UDP-glucuronosyltransferases (UGTs). UGT2B17 has been shown to be particularly active against androgens and is highly abundant in the prostate. Recently, we discovered that deletion of the UGT2B17 gene is associated with low or undetectable urinary testosterone levels. Here, we determined the phenotypic outcome of the deletion by quantifying the UGT2B17 mRNA expression in normal prostate tissues in individuals with different genotypes. Additionally, the frequency of UGT2B17 deletion polymorphism was studied in a Swedish population-based case-control study including 176 patients diagnosed with prostate cancer and 161 controls. We found that the individuals homozygous for the insertion allele expressed 30 times more UGT2B17 mRNA in prostate tissue than the heterozygotes. Carriers of the deletion allele had a significantly increased risk of prostate cancer (OR=2.07; 95% CI=1.32-3.25). In conclusion, these results show the UGT2B17 deletion polymorphism is associated with prostate cancer risk.

Body size and prostate cancer: a 20-year follow-up study among 135006 Swedish construction workers.

BACKGROUND: Obesity is associated with endocrine changes (e.g., increased estrogen and decreased testosterone in the blood) that have been implicated in the cause of prostate cancer and, therefore, an association between body weight and the risk of developing prostate cancer would be expected. However, because of bias or low statistical power in previous epidemiologic studies, associations between anthropometric measurements (height and weight), body mass index (BMI), and the risk of prostate cancer may have been inadvertently overlooked. PURPOSE: We performed a large, retrospective cohort study among Swedish construction workers to evaluate possible associations of adult weight, height, BMI, and lean body mass (LBM) by age at entry in the study with the incidence and mortality rate of prostate cancer. METHODS: We analyzed data that had been compiled in a computerized central register on a cohort of approximately 135000 male construction workers. Information on height and weight had been collected with the use of a comprehensive questionnaire filled out by nurses at the time of enrollment in the cohort, from 1971 through 1975. Complete follow-up was achieved through 1991 by means of record linkage to the Swedish National Cancer Register, the Death Register, and the Migration Register. A total of 2368 incident cases and 708 deaths from prostate cancer occurred in the cohort during a follow-up period averaging 18 years. We used only information obtained at the index visit from 1971 through 1975 to determine age-adjusted rate ratios (RRs) in a Poisson-based multiplicative multivariate model with age and the relevant exposure variable (e.g., weight, height, BMI, and LBM) as independent variables. RESULTS: All anthropometric measurements were positively associated with the risk of prostate cancer and were more strongly related to mortality than to incidence. The excess risk of death from prostate cancer was statistically significant in all BMI categories above the reference category: RR = 1.40 (95% confidence interval [CI] = 1.09-1.81) in the highest category compared with the lowest (P for trend = .04). For height and LBM, the excess risk in the highest compared with the lowest categories was somewhat less pronounced: RR = 1.28 (95% CI = 1.02-1.60) and RR = 1.26 (95% CI = 1.02-1.57), respectively. Statistically significant linear dose-response relationships were also found with the incidence of prostate cancer, with the exception of BMI (P for trend = .10). CONCLUSION: Our large cohort study indicates that various aspects of body size are related to the risk of prostate cancer and that future studies are needed to study the role of body size and prostate cancer.

Insulin-like growth factor 1 and prostate cancer risk: a population-based, case-control study.

BACKGROUND: Recent epidemiologic investigations have suggested an association between increased blood levels of insulin-like growth factor 1 (IGF-1) and increased risk of prostate cancer. Our goal was to determine whether an association exists between serum levels of IGF-1 and one of its binding proteins, insulin-like growth factor-binding protein 3 (IGFBP-3), and prostate cancer risk. METHODS: An immunoradiometric assay was used to quantify IGF-1 levels and IGFBP-3 levels in serum samples as part of a population-based, case-control study in Sweden. The study population comprised 210 patients with newly diagnosed, untreated prostate cancer and 224 frequency-matched control subjects. Data were analyzed by use of unconditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Reported P values are two-sided. RESULTS: The mean serum IGF-1 level for case patients (158.4 ng/mL) was significantly higher than that for control subjects (147.4 ng/mL) (P = .02); corresponding mean serum IGFBP-3 levels were not significantly different between case patients (2668 ng/mL) and control subjects (2518 ng/mL) (P =.09). We found a moderately strong and statistically significant (P = .04) positive association between serum levels of IGF-1 levels and risk of prostate cancer (OR = 1.51; 95% CI = 1.0-2.26 per 100 ng/mL increment); the association was particularly strong for men younger than 70 years of age (OR = 2.93; 95% CI = 1.43-5.97). No association was found between serum IGF-1 levels and disease stage. Serum IGFBP-3 levels were not significantly associated with increased risk of disease, and adjustment for IGFBP-3 had little effect on the association between IGF-1 levels and risk of prostate cancer. CONCLUSION: Elevated serum IGF-1 levels may be an important predictor of risk for prostate cancer. However, our results do not support an important role for serum IGFBP-3 as a predictor of risk for this disease.

Polymorphisms in NAT2, CYP2D6, CYP2C19 and GSTP1 and their association with prostate cancer.

The development of prostate cancer is dependent on heredity, androgenic influences, and exposure to environmental agents. A high intake of dietary fat is associated with an increased risk of prostate cancer, either through influence on steroid hormone profiles or through production of carcinogenic compounds that require biotransformation by enzymes. The polymorphic glutathione S-transferase (GST), N-acetyltransferase (NAT), and cytochrome P450 (CYP) enzymes are of particular interest in prostate cancer susceptibility because of their ability to metabolize both endogenous and exogenous compounds, including dietary constituents. Association between different NAT2, CYP2D6, CYP2C19 and GSTP1 genotypes and prostate cancer was studied in a Swedish and Danish case-control study comprising 850 individuals. The combined Swedish and Danish study population was analysed by polymerase chain reaction for the NAT2 alleles *4, *5A, *5B, *5C, *6 and *7, and for the CYP2D6 alleles *l, *3 and *4. The Swedish subjects were also analysed for the CYP2C19 alleles *1 and *2, and the GSTP1 alleles *A, *B and *C. No association was found between prostate cancer and polymorphisms in NAT2, CYP2D6, CYP2C19 or GSTP1. An association between CYP2D6 poor metabolism and prostate cancer was seen among smoking Danes; odds ratio 3.10 (95% confidence interval 1.07; 8.93), P = 0.03, but not among smoking Swedes; odds ratio 1.19 (95% confidence interval 0.41; 3.42), P = 0.75. Smoking is not a known risk factor for prostate cancer, and the association between CYP2D6 poor metabolism and prostate cancer in Danish smokers may have arisen by chance.

Early life risk factors for prostate cancer: a population-based case-control study in Sweden.

We undertook a population-based case-control study to investigate early life risk factors for prostate cancer. Information on dietary habits during childhood and adolescence, childhood environment, pubertal development, and physical activity was collected by face-to-face interviews with 256 (74.6%) of all eligible cases and 252 (76.6%) of all selected controls, frequency matched by age. All potential controls were screened for prostate cancer with negative findings. Odds ratios with 95% confidence intervals were estimated by logistic regression. Analyses of localized (T0-2' M0) and more advanced cancers were made separately. In general, there was no clear association between diet and prostate cancer risk. An increased risk associated with childhood living in more densely populated, compared with rural, areas was found (odds ratio = 2.1; 95% confidence interval = 1.3-3.5); this effect was most apparent for localized cancers (odds ratio = 3.2' 95% confidence interval = 1.7-6.2). There was no substantial association between adult height or body mass index and prostate cancer, but exercise appeared negatively associated with risk (P value for trend, 0.13). We conclude that our study provides some indications that exposures early in life are important in the etiology of prostate cancer.

Lifestyle factors and prostate cancer risk: a case-control study in Sweden.

We examined associations between lifestyle factors and subsequent risk of prostate cancer in a population-based case-control study. Information on smoking and alcohol habits, socioeconomic factors, marital status, family history, and sexual habits were obtained from a questionnaire and a face-to-face interview with 256 (74.6%) eligible patients and 252 (76.6%) selected controls, frequency matched by age and screened for prostate cancer with negative findings. Unconditional logistic regression was used to estimate the odds ratios (ORs). Risk was elevated among current smokers of cigarettes (OR, 1.8) and current users of hard liquor (OR, 1.4); however, the lack of dose-response trend for both of these exposures argues against a causal association. We found tentative evidence that early first intercourse, a larger number of sexual partners, and other indices of high sexual activity are associated with increased risk. Similarly, adult height, an indicator of nutrition during childhood and adolescence, was weakly positively associated with risk, although larger studies are needed to establish this link. Unmarried men had a lower risk than married men (OR, 0.3), and socioeconomic status did not appear to be strongly associated with prostate cancer. Men with a father who had prostate cancer had a more than 2-fold increased risk of prostate cancer, whereas those with a brother affected had about a 5-folk risk.

Clinical evaluation of flutamide and estramustine as initial treatment of metastatic carcinoma of prostate.

The efficacy and side effects of flutamide were compared with estramustine in patients with advanced prostatic carcinoma. Thirty patients with metastatic cancers but with no serious cardiovascular (CV) conditions were randomly assigned to receive treatment either with flutamide (250 mg X 3) or with estramustine (280 mg X 2). Clinical examination, bone scan, laboratory measurements, including coagulation studies were performed prior to randomization, every three months during year one, and at six-month intervals thereafter. The two groups were comparable with respect to age and tumor characteristics. However, more patients presented with skeletal pain among those later treated with flutamide. During an observation period of between one and two and one-half years, flutamide was discontinued in 1 case (7%) because of icterus, and estramustine in 3 cases (20%) because of CV complications. Of the remaining 14 flutamide-treated patients, 13 responded initially. Eleven of them relapsed, and 5 died of cancer. In the corresponding group of 12 estramustine-treated patients, there were 11 primary responders. Of these, only 2 relapsed and died as did the only nonresponder. The difference between the two groups with regard to relapse is significant (P less than 0.01), but not with regard to mortality. All estramustine-treated patients lost their libido, whereas only 20 per cent of the patients treated with flutamide did so. In the present limited material there was an initial favorable response to flutamide without signs of CV complications and with maintained libido in most cases. However, due to significantly increased risk for relapse compared with estramustine, flutamide cannot be recommended as single therapy except in cases where estrogens are contraindicated or when interference with libido and potency is unacceptable.

Clinical evaluation with long-term follow-up of flutamide and estramustine as initial treatment of metastatic carcinoma of the prostate.

Thirty patients with metastatic cancers but with no serious cardiovascular (CV) conditions were randomly assigned to receive treatment either with flutamide (250 mg x 3) (F) or with estramustine (280 mg x 2) (E). Clinical examination, bone scan, laboratory measurements were performed before randomization and at regular intervals thereafter. During an observation period of between 1 and 2.5 years, F was discontinued in one case (7%) because of icterus, and E in three cases (20%) because of CV complications. Of the remaining 14 F-treated patients, 13 responded initially. Eleven of them relapsed, and five died of cancer. In the corresponding group of 12 E-treated patients, there were 11 primary responders. Of these, only two relapsed and died, as did the only nonresponder. The difference between the two groups with regard to relapse is significant (p less than 0.01), but not with regard to mortality. In the present material, there was an initial favorable response to F without signs of CV complications and with maintained libido in most cases. However, due to the significantly increased risk for relapse compared with E, F cannot be recommended as single therapy except in cases where estrogens are contraindicated or when interference with libido and potency is unacceptable.

Optimized urinary microscopy for assessment of bacteriuria in primary care.

Microscopy of wet-stained urinary sediment as an indicator of bacteriuria was evaluated in 418 consecutive primary care visits in a small community. Delivery of morning urine was encouraged and contributed to bladder incubation times of 4 or more hours in 79% of the visits; the overall culture positivity was about 80%. Bacteria or leukocytes alone or together as minimal requirements were suboptimal microscopy criteria for bacteriuria, whereas a minimum of moderate amounts of bacteria or 5 leukocytes per high-power field (x400) as a cutoff point yielded the best diagnostic accuracy. Optimization of urinary sediment microscopy in this way resulted in a desirable high sensitivity (97%) and efficacy (86%) in acutely symptomatic patients, as well as reasonably high efficacy (79%) in other patients, independent of sex or bladder incubation time. The method's simplicity and speed recommend it for use in primary care, particularly in patients with acute symptoms of urinary tract infection.