Subsequent Risk Of Prostate Cancer Research Articles

An initial melanoma diagnosis may increase the subsequent risk of prostate cancer: Results from the New South Wales Cancer Registry

Emerging evidence suggests that a diagnosis of cutaneous melanoma (CM) may be associated with prostate cancer (PC) incidence. We examined if the incidence of CM was associated with an increased subsequent risk of PC. We used data from the New South Wales Cancer Registry for all CM and PC cases diagnosed between January 1972 and December 2008. We calculated the age standardized incidence ratio (SIR) and 95% confidence intervals (95% CI) for PC incidence following a CM diagnosis, applying age- and calendar- specific rates to the appropriate person years at risk. We determined rate ratio (RR) and 95% CI of PC incidence according to specified socio-demographic categories and disease related characteristics, using a negative binomial model. There were 143,594 men diagnosed with PC or CM in the study period and of these 101,198 and 42,396 were diagnosed with PC and CM, respectively, as first primary cancers. Risk of PC incidence increased following CM diagnosis (n = 2,114; SIR = 1.25; 95% CI:1.20.8-1.31: p < 0.0001), with the increased risk apparent in men diagnosed with localised CM (n = 1,862;SIR = 1.26; 95% CI:1.20–1.32). CM diagnosis increased the subsequent risk of PC incidence. This raises the potential for future PC risk to be discussed with newly diagnosed males with CM.

Antiarrhythmic drug usage and prostate cancer: a population-based cohort study

Even though the relationship between antiarrhythmic drug usage and subsequent prostate cancer (PCa) risk has recently been highlighted, relevant findings in the previous literature are still inconsistent. In addition, very few studies have attempted to investigate the association between sodium channel blockers or potassium channel blockers for arrhythmia and the subsequent PCa risk. Therefore, this cohort study aimed to find the relationship between antiarrhythmic drug usage and the subsequent PCa risk using a population-based dataset. The data used in this study were derived from the Longitudinal Health Insurance Database 2005, Taiwan, China. We respectively identified 9988 sodium channel blocker users, 3663 potassium channel blocker users, 65 966 beta-blocker users, 23 366 calcium channel blockers users, and 7031 digoxin users as the study cohorts. The matched comparison cohorts (one comparison subject for each antiarrhythmic drug user) were selected from the same dataset. Each patient was tracked for a 5-year period to define those who were subsequently diagnosed with PCa. After adjusting for sociodemographic characteristics, comorbidities, and age, Cox proportional hazard regressions found that the hazard ratio (HR) of subsequent PCa for sodium channel blocker users was 1.12 (95% confidence interval [CI]: 0.84–1.50), for potassium channel blocker users was 0.89 (95% CI: 0.59–1.34), for beta-blocker users was 1.08 (95% CI: 0.96–1.22), for calcium channel blocker users was 1.14 (95% CI: 0.95–1.36), and for digoxin users was 0.89 (95% CI: 0.67–1.18), compared to their matched nonusers. We concluded that there were no statistical associations between different types of antiarrhythmic drug usage and subsequent PCa risk.

Lower Urinary Tract Infection and Subsequent Risk of Prostate Cancer: A Nationwide Population-Based Cohort Study.

PurposeWe investigated whether lower urinary tract infection (LUTI), including cystitis or urethritis, is associated with an increased risk of developing prostate cancer (PCa), in a nationwide population-based cohort study.MethodsWe identified 14,273 men newly diagnosed with LUTI (9347 with cystitis, and 4926 with urethritis) between 1998 and 2011, from the Taiwan Longitudinal Health Insurance Database 2000. Each patient was randomly frequency-matched with 4 men without LUTI, based on age and index year of diagnosis. Cox’s proportional hazard regression analysis was performed to estimate the effect of LUTI on the PCa risk.ResultsThe risk of developing PCa was significantly higher in the cystitis cohort (adjusted HR = 1.46, 95% CI = 1.20–1.78) and in the urethritis cohort (adjusted HR = 1.72, 95% CI = 1.26–2.34) than in the group without LUTI. Further analyses indicated that patients with more than 5 medical visits for LUTI per year had a significantly greater risk of developing PCa.ConclusionWe found that cystitis or urethritis may play an etiological role in the development of PCa in Taiwanese men, particularly in those with repeated medical visits for cystitis or urethritis. Further studies are warranted on the association between LUTI and PCa in other countries, particularly where the prevalence of PCa is high.

Plasma 25-hydroxy vitamin D and subsequent prostate cancer risk in a nested Case-Control study in Japan: The JPHC study.

Although vitamin D has been experimentally reported to inhibit tumorigenesis, cell growth and prostate cancer invasion, epidemiologic data regarding prostate cancer risk are inconsistent, and some studies have suggested positive but nonsignificant associations. Further, the impact of vitamin D on prostate cancer between Western and Japanese populations may differ due to different plasma vitamin D levels. We performed a nested case-control study within the Japan Public Health Center-based Prospective (JPHC) Study in 14,203 men (40-69 years) who answered a self-administered questionnaire at baseline (1990-1994) and gave blood samples, and were followed until 2005. We identified 201 prostate cancers which are newly diagnosed during follow-up (mean 12.8 years). We selected two matched controls for each case from the cohort. We used a conditional logistic regression model to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for prostate cancer with respect to levels of 25-hydroxy vitamin D (25(OH)D) in plasma. We did not observe statistically significant association between 25(OH)D level and total prostate cancer (multivariate OR=1.13 (95%CI=0.66-1.94, Ptrend=0.94) for the highest versus lowest tertile) However, 25(OH) levels were slightly positively associated with advanced cancer. The results remained substantially unchanged after stratification by intake of fish or calcium intake. 25(OH)D level showed no association with overall prostate cancer among Japanese men in this large cohort.

Is birthweight associated with total and aggressive/lethal prostate cancer risks? A systematic review and meta-analysis

Background:It has been hypothesised that intrauterine exposures are important for subsequent prostate cancer risk. Prior epidemiological studies have used birthweight as a proxy of cumulative intrauterine exposures to test this hypothesis, but results have been inconsistent partly because of limited statistical power.Methods:We investigated birthweight in relation to prostate cancer in the Medical Research Council (MRC) National Survey of Health and Development (NSHD) using Cox proportional hazards models. We then conducted a meta-analysis of birthweight in relation to total and aggressive/lethal prostate cancer risks, combining results from the NSHD analysis with 13 additional studies on this relationship identified from a systematic search in four major scientific literature databases through January 2015.Results:Random-effects models found that per kg increase in birthweight was positively associated with total (OR=1.02, 95% confidence interval (95% CI)=1.00, 1.05; I2=13%) and aggressive/lethal prostate cancer (OR=1.08, 95% CI=0.99, 1.19; I2=40%). Sensitivity analyses restricted to studies with birthweight extracted from medical records demonstrated stronger positive associations with total (OR=1.11, 95% CI=1.03, 1.19; I2=0%) and aggressive/lethal (OR=1.37, 95% CI=1.09, 1.74; I2=0%) prostate cancer. These studies heavily overlapped with those based in Nordic countries.Conclusions:This study provides evidence that heavier birthweight may be associated with modest increased risks of total and aggressive/lethal prostate cancer, which supports the hypothesis that intrauterine exposures may be related to subsequent prostate cancer risks.

Racial differences in the relationship between clinical prostatitis, presence of inflammation in benign prostate and subsequent risk of prostate cancer.

Epidemiologic studies, primarily done in white men, suggest that a history of clinically-diagnosed prostatitis increases prostate cancer risk, but that histological prostate inflammation decreases risk. The relationship between a clinical history of prostatitis and histologic inflammation in terms of how these two manifestations of prostatic inflammation jointly contribute to prostate cancer risk and whether racial differences exist in this relationship is uncertain. Using a nested design within a cohort of men with benign prostate tissue specimens, we analyzed the data on both clinically-diagnosed prostatitis (NIH categories I-III) and histological inflammation in 574 prostate cancer case-control pairs (345 white, 229 African American). Clinical prostatitis was not associated with increased prostate cancer risk in the full sample, but showed a suggestive inverse association with prostate cancer in African Americans (odds ratio (OR)=0.47; 95% confidence interval (CI)=0.27-0.81). In whites, clinical prostatitis increased risk by 40%, but was only associated with a significant increased prostate cancer risk in the absence of evidence of histological inflammation (OR=3.56; 95% CI=1.15-10.99). Moreover, PSA velocity (P=0.008) and frequency of PSA testing (P=0.003) were significant modifiers of risk. Clinical prostatitis increased risk of prostate cancer almost three-fold (OR=2.97; 95% CI=1.40-6.30) in white men with low PSA velocity and about twofold in white men with more frequent PSA testing (OR=1.91; 95% CI=1.09-3.35). In our cohort of men with benign prostate specimens, race, and histological inflammation were important cofactors in the relationship between clinical prostatitis and prostate cancer. Clinical prostatitis was associated with a slightly decreased risk for prostate cancer in African American men. In white men, the relationship between clinical prostatitis and prostate cancer risk was modified by histological prostatic inflammation, PSA velocity, and frequency of PSA testing-suggesting a complex interplay between these indications of prostatic inflammation and prostate cancer detection.

Intermediate-Term Risk of Prostate Cancer is Directly Related to Baseline Prostate Specific Antigen: Implications for Reducing the Burden of Prostate Specific Antigen Screening

Prostate specific antigen screening is controversial, as a large number of men must be screened annually to achieve a benefit. We sought to determine whether baseline prostate specific antigen could reliably predict subsequent risk of prostate cancer and risk of consequential prostate cancer. A multiethnic cohort of 2,923 prostate cancer-free men was recruited between 2000 and 2012, and followed for a median of 7.5 years. Baseline prostate specific antigen was stratified into 6 strata and relative hazards of prostate cancer detection for each prostate specific antigen stratum were estimated, adjusting for ethnicity, family history and age. During followup 289 patients were diagnosed with prostate cancer. Men with baseline prostate specific antigen in the lowest stratum (0.1 to 1.0 ng/ml) were at greatly reduced risk for prostate cancer during followup. This half of the cohort with prostate specific antigen 1.0 ng/ml or less were at 3.4% (95% CI 2.1, 4.5) 10-year risk of prostate cancer and 90% of the cancers were low risk. By comparison the other half were at 15% to 39% risk of cancer detection with a 39% risk in the highest stratum (3 to 10 ng/ml). Optimal prostate specific antigen screening frequency for men with aprostate specific antigen level of 0.1 to 1.0 ng/ml may be up to every 10 years. Thisapproach has the potential to dramatically reduce the cost of screening, decreasing over detection of inconsequential tumors, while maintaining detection of tumors for which treatment has been proven to reduce prostate cancer mortality.

Fiber intake and risk of subsequent prostate cancer in Japanese men

Dietary fiber may reduce the risk of prostate cancer, possibly by increasing circulating concentrations of sex hormone-binding globulin and improving insulin sensitivity. However, results from previous epidemiologic studies of fiber intake and prostate cancer are inconsistent, and to our knowledge, no study has comprehensively evaluated the effects of soluble and insoluble fiber on prostate cancer in Asia. The objective was to examine the association between fiber intake and prostate cancer in Japanese men. We conducted a population-based prospective study in 43,435 Japanese men aged 45-74 y. Participants responded to a validated questionnaire, which included 138 food items. Follow-up was from 1995 through 2009. HRs and 95% CIs of incidence were calculated according to quartiles of fiber intake. During the 11.6-y follow-up, of the 825 men newly diagnosed with prostate cancer, 213 had advanced-stage cancer, 582 had organ-localized disease, and 30 had an undetermined stage of disease. Among them, 217 cases were detected by subjective symptoms. Total fiber was not associated with total or advanced prostate cancer, with respective multivariable HRs for the highest and lowest quartiles of 1.00 (95% CI: 0.77, 1.29; P-trend = 0.97) and 0.67 (95% CI: 0.42, 1.07; P-trend = 0.30). Total fiber and insoluble fiber intake were associated with a decreased risk of advanced cancers detected by subjective symptoms, with multivariate HRs (95% CIs) across increasing quartiles of 1.00, 0.58, 0.62, and 0.44 (0.21, 0.92; P-trend = 0.05) for total fiber and 1.00, 0.60, 0.52, and 0.46 (0.22, 0.93; P-trend = 0.04) for insoluble fiber. Soluble fiber intake showed no association with prostate cancer. Dietary fiber is inversely associated with advanced prostate cancer detected by subjective symptoms even among populations with relatively low intake, such as Japanese. These results suggest that a very low intake of dietary fiber is associated with an increased risk of prostate cancer.

Diabetes mellitus and risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition.

The current epidemiologic evidence suggests that men with type 2 diabetes mellitus may be at lower risk of developing prostate cancer, but little is known about its association with stage and grade of the disease. The association between self-reported diabetes mellitus at recruitment and risk of prostate cancer was examined in the European Prospective Investigation into Cancer and Nutrition (EPIC). Among 139,131 eligible men, 4,531 were diagnosed with prostate cancer over an average follow-up of 12 years. Multivariable hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards models stratified by EPIC-participating center and age at recruitment, and adjusted for education, smoking status, body mass index, waist circumference, and physical activity. In a subset of men without prostate cancer, the cross-sectional association between circulating concentrations of androgens and insulin-like growth factor proteins with diabetes status was also investigated using linear regression models. Compared to men with no diabetes, men with diabetes had a 26% lower risk of prostate cancer (HR, 0.74; 95% CI, 0.63-0.86). There was no evidence that the association differed by stage (p-heterogeneity, 0.19) or grade (p-heterogeneity, 0.48) of the disease, although the numbers were small in some disease subgroups. In a subset of 626 men with hormone measurements, circulating concentrations of androstenedione, total testosterone and insulin-like growth factor binding protein-three were lower in men with diabetes compared to men without diabetes. This large European study has confirmed an inverse association between self-reported diabetes mellitus and subsequent risk of prostate cancer.

Alcohol and smoking and subsequent risk of prostate cancer in Japanese men: The Japan Public Health Center‐based prospective study

Although alcohol and smoking have not been established as risk factors for prostate cancer, they are important risk factors for other human cancers and potentially major avoidable factors. Alcohol drinkers and smokers might be less likely to get screening, which might lead to attenuation of the positive association. Here, we investigated the association of alcohol drinking and smoking and prostate cancer according to stage, as well as prostate cancer detected by subjective symptoms, in a large prospective study among Japanese men. The Japan Public Health Center-based prospective study (JPHC study) was established in 1990 for Cohort I and in 1993 for Cohort II. Subjects were 48,218 men aged 40-69 years who completed a questionnaire, which included their alcohol and smoking habits at baseline, and who were followed until the end of 2010. During 16 years of follow-up, 913 men were newly diagnosed with prostate cancer; of whom 248 had advanced cases, 635 were organ-localized and 30 were of an undetermined stage. Alcohol consumption was dose-dependently associated with advanced prostate cancer [nondrinkers: reference, 0-150 g/week: hazard ratio (HR) = 1.23, 95% confidence interval (CI) = 0.83-1.82; 150-300 g/week: HR = 1.51, 95% CI = 1.04-2.19; ≥ 300 g/week: HR = 1.41, 95% CI = 0.97-2.05, p for trend = 0.02]. The positive association was not substantially changed among cancers detected by subjective symptoms. Smoking was inversely associated with prostate cancer among total subjects, but tended to increase the risk of advanced prostate cancer detected by subjective symptoms. In conclusion, abstinence from alcohol and prohibition of smoking might be important factors in the prevention of advanced prostate cancer.

Histological inflammation and risk of subsequent prostate cancer among men with initially elevated serum prostate‐specific antigen (PSA) concentration in the Finnish prostate cancer screening trial

To assess whether histological signs of inflammation are associated with an increased risk of subsequent prostate cancer (PCa) in men with elevated serum prostate-specific antigen (PSA) concentrations and benign initial biopsy. Study subjects were men aged 54-67 years with an elevated PSA (≥4 ng/mL or 3-4 ng/mL and free to total PSA ratio ≤0.16 or positive digital rectal examination), but a benign biopsy result within the Finnish population-based randomised screening trial for PCa, which started in 1996. A total of 293 prostate biopsies without PCa or suspicion of malignancy from the first screening round in the Tampere centre were re-evaluated by a uropathologist to assess histological inflammation. Results of the subsequent screening rounds were obtained from the trial database and PCa diagnoses made outside the screening were obtained from the Finnish Cancer Registry. The median length of follow-up was 10.5 years. Cox regression analysis was used to assess PCa risk after the initial benign biopsy. Histological inflammation was found in 66% of the biopsies. Subjects with inflammation at the biopsy had a slightly lower PCa risk in the second screening round (18 vs 27%, rate ratio 0.69, 95% confidence interval [CI] 0.35-1.34) relative to men without inflammation. In further follow-up, the PCa risk remained nonsignificantly lower (hazard ratio [HR] 0.71, CI 0.46-1.10; P = 0.13). The risk was not appreciably affected by adjustment for age, PSA, prostate volume and family history of PCa (HR 0.67, CI 0.42-1.07; P = 0.092). Histological inflammation in a prostate biopsy among men with an initial false-positive screening test was not associated with an increased risk of subsequent PCa, but instead with a decreased risk which was of borderline significance. Inflammation in prostate biopsy is not a useful risk indicator in PCa screening.

Baseline prostate-specific antigen measurements and subsequent prostate cancer risk in the Danish Diet, Cancer and Health cohort

AimAlthough prostate-specific antigen (PSA) screening reduces mortality from prostate cancer, substantial over-diagnosis and subsequent overtreatment are concerns. Early screening of men for PSA may serve to stratify the male population by risk of future clinical prostate cancer. Methods and materialCase–control study nested within the Danish ‘Diet, Cancer and Health’ cohort of 27,179 men aged 50–64 at enrolment. PSA measured in serum collected at cohort entry in 1993–1997 was used to evaluate prostate cancer risk diagnosed up to 14years after. We identified 911 prostate cancer cases in the Danish Cancer Registry through 31st December 2007 1:1 age-matched with cancer-free controls. Aggressive cancer was defined as ⩾T3 or Gleason score ⩾7 or N1 or M1. Statistical analyses were based on conditional logistic regression with age as underlying time axis. ResultsTotal PSA and free-to-total PSA ratio at baseline were strongly associated with prostate cancer risk up to 14years later. PSA was grouped in quintiles and free-to-total PSA ratio divided in three risk groups. The incidence rate ratio for prostate cancer was 150 (95% confidence interval, 72–310) among men with a total PSA in the highest quintile (>5.1ng/ml) compared to the lowest (<0.80ng/ml). The risk of aggressive cancer was highly elevated in men with a PSA level in the highest quintile. The results indicate that one-time measurement of PSA could be used in an individualised screening strategy, sparing a large proportion of men from further PSA-based screening.

2‐Amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP)‐DNA adducts in benign prostate and subsequent risk for prostate cancer

Despite convincing evidence that 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)--a heterocyclic amine generated by cooking meats at high temperatures--is carcinogenic in animal models, it remains unclear whether PhIP exposure leads to increased cancer risk in humans. PhIP-DNA adduct levels were measured in specimens from 534 prostate cancer case-control pairs nested within a historical cohort of men with histopathologically benign prostate specimens. We estimated the overall and race-stratified risk of subsequent prostate cancer associated with higher adduct levels. PhIP-DNA adduct levels in benign prostate were significantly higher in Whites than African Americans (0.274 optical density units (OD) ±0.059 vs. 0.256 OD ±0.054; p<0.0001). Prostate cancer risk for men in the highest quartile of PhIP-DNA adduct levels was modestly increased [odds ratio (OR) = 1.25; 95% confidence interval (CI) = 0.76-2.07]. In subset analyses, the highest risk estimates were observed in White patients diagnosed more than 4 years after cohort entry (OR = 2.74; 95% CI = 1.01-7.42) or under age 65 (OR = 2.80; 95% CI = 0.87-8.97). In Whites, cancer risk associated with high-grade prostatic intraepithelial neoplasia combined with elevated PhIP-DNA adduct levels (OR = 3.89; 95% CI = 1.56-9.73) was greater than risk associated with either factor alone. Overall, elevated levels of PhIP-DNA adducts do not significantly increase prostate cancer risk. However, our data show that White men have higher PhIP-DNA adduct levels in benign prostate tissue than African American men, and suggest that in certain subgroups of White men high PhIP-DNA adduct levels may predispose to an increased risk for prostate cancer.

Methylation of the RARB Gene Increases Prostate Cancer Risk in Black Americans

Gene promoter hypermethylation may be useful as a biomarker for cancer risk in histopathologically benign prostate specimens. We performed a nested case-control study of gene promoter methylation status for 5 genes (APC, RARB, CCND2, RASSF1 and MGMT) measured in benign biopsy specimens from 511 prostate cancer case-control pairs. We estimated the overall and race stratified risk of subsequent prostate cancer associated with methylation status. On race stratified analysis RARB methylation was associated with a higher cancer risk in black American men (OR 2.18, 95% CI 1.39-3.44). APC methylation was associated with an increased risk of high grade tumors (OR 2.43, 95% CI 1.20-4.90), which was higher in black than in white men (OR 3.21 vs 2.04). In cases RARB and APC gene methylation in benign prostate samples persisted in matched malignant specimens. In black cases the combined risk associated with RARB and APC methylation (OR 3.04, 95% CI 1.44-6.42) was greater than the individual risk of each gene and significantly different from that in white cases (OR 1.14, 95% CI 0.56-2.30). RARB gene methylation in histopathologically benign prostate samples was associated with a statistically significant increased risk of subsequent prostate cancer in black men. Methylation data on additional genes may improve risk stratification and clinical decision making algorithms for cancer screening and diagnosis.

Elevated polycyclic aromatic hydrocarbon-DNA adducts in benign prostate and risk of prostate cancer in African Americans.

Carcinogen-DNA adducts, a marker of DNA damage, are capable of inducing mutations in oncogenes and tumor suppressor genes, resulting in carcinogenesis. We have shown previously that polycyclic aromatic hydrocarbon (PAH)-DNA adduct levels in prostate cancer cases vary by cellular histology and that higher adduct levels are associated with biochemical recurrence. A nested case-control study was conducted in a historical cohort of 6692 men with histopathologically benign prostate specimens. PAH-DNA adduct levels were determined by immunohistochemistry in benign prostate specimens from 536 prostate cancer case-control pairs (59% White and 41% African American). We estimated the overall and race-stratified risk of subsequent prostate cancer associated with higher adduct levels. Prostate cancer risk for men with elevated adduct levels (defined as greater than control group median) was slightly increased [odds ratio (OR) = 1.28, 95% confidence interval (CI) = 0.98-1.67, P = 0.07]. After race stratification, elevated adduct levels were significantly associated with increased risk in African American men (OR = 1.56, CI = 1.00-2.44, *P = 0.05) but not White men (OR = 1.14, CI = 0.82-1.59, P = 0.45). Elevated PAH-DNA adduct levels were significantly associated with 60% increased risk of prostate cancer among cases diagnosed 1-4 years after cohort entry (OR = 1.60, CI = 1.07-2.41) with a greater risk observed in African Americans within the first 4 years of follow-up (OR = 4.71, CI = 1.97-11.26, ***P = 0.0005). Analyses stratified by age or tumor grade revealed no additional significant heterogeneity in risk. Increased prostate cancer risk associated with high PAH-DNA adduct levels in benign prostate was found only in African Americans; risk was greatest within 4 years of follow-up, possibly reflecting a carcinogenic process not yet histologically detectable.

Insulin-like Growth Factor-I Concentration and Risk of Prostate Cancer: Results from the European Prospective Investigation into Cancer and Nutrition

High circulating insulin-like growth factor-I (IGF-I) concentrations have been associated with increased risk for prostate cancer in several prospective epidemiological studies. In this study, we investigate the association between circulating IGF-I concentration and risk of prostate cancer over the long term in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. In a nested case-control design, 1,542 incident prostate cancer cases from eight European countries were individually matched to 1,542 controls by study center, age at recruitment, duration of follow-up, time of day, and duration of fasting at blood collection. Conditional logistic regression models were used to calculate risk for prostate cancer associated with IGF-I concentration, overall and by various subgroups. Circulating IGF-I concentration was associated with a significant increased risk for prostate cancer [OR for highest vs. lowest quartile, 1.69; 95% confidence interval (CI), 1.35-2.13; P(trend) = 0.0002]. This positive association did not differ according to duration of follow-up [ORs for highest vs. lowest quartile were 2.01 (1.35-2.99), 1.37 (0.94-2.00), and 1.80 (1.17-2.77) for cancers diagnosed <4, 4-7, and >7 years after blood collection, respectively (P(heterogeneity) = 0.77)] or by stage, grade, and age at diagnosis or age at blood collection (all subgroups P(heterogeneity) >0.05). In this European population, high circulating IGF-I concentration is positively associated with risk for prostate cancer over the short and long term. As IGF-I is the only potentially modifiable risk factor so far identified, research into the effects of reducing circulating IGF-I levels on subsequent prostate cancer risk is warranted.

Fatherhood and prostate cancer risk in a population-based case-control study

Fatherhood and prostate cancer risk in a population-based case-control study

A Population-Based Nested Case-Control Study in Taiwan: Use of 5α-Reductase Inhibitors Did Not Decrease Prostate Cancer Risk in Patients with Benign Prostate Hyperplasia

5α-Reductase inhibitors (5ARIs) are commonly used to treat benign prostate hyperplasia (BPH) by blocking the conversion of testosterone into the more potent dihydrotestosterone. This study explored a possible association between the use of the 5ARIs finasteride and dutasteride and the subsequent risk of prostate cancer or other cancers. We analyzed data from the Taiwanese National Health Insurance system. In a BPH cohort, we identified 1,489 patients with cancer and included them in our study group. For the control group, 3 patients without cancer were frequency matched with each BPH case for age, BPH diagnosis year, index year, and month. Information regarding past 5ARI use was obtained from the Taiwanese National Health Insurance Research Database (NHIRD). Multivariate logistic regression analysis was conducted, and odds ratio (OR) and 95% confidence interval (CI) were estimated. Finasteride use marginally increased the incidence of prostate and overall cancer at a level of statistical significance (prostate cancer: OR = 1.90; 95% CI: 1.00-3.59; overall cancer: OR = 1.51; 95% CI: 1.00-2.28). Dutasteride use significantly increased kidney cancer risk (OR = 9.68, 95% CI: 1.17-80.0). Dosage analysis showed that lower doses of finasteride were associated with higher overall and prostate cancer risks. The major limitation is the lack of important data in the NHIRD, such as prostate cancer histologic grades, smoking habits, alcohol consumption, body mass index, socioeconomic status, and family history of cancer. This population-based nested case-control study suggested that finasteride use may increase prostate and overall cancer risks for patients with BPH. The effects were more prominent for patients using lower doses of finasteride.

Plasma total, LDL, and HDL cholesterol and risk of aggressive prostate cancer in the Cancer Prevention Study II Nutrition Cohort

Some recent studies have suggested that higher total cholesterol levels are positively associated with risk of aggressive prostate cancer. However, evidence about this association is limited and few studies examined cholesterol subfractions. We therefore examined associations of total, LDL, and HDL cholesterol concentrations with subsequent risk of aggressive prostate cancer within the Cancer Prevention Study II Nutrition Cohort. A total of 14,241 men with no history of cancer provided a blood sample between 1998 and 2001. During follow-up through 2007, 236 of these men were diagnosed with aggressive prostate cancer (AJCC stage≥III or Gleason score≥7 (4+3)). Plasma total, LDL, and HDL cholesterol concentrations were measured in these 236 cases and 236 age and race-matched controls. Multivariable-adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression, adjusting for use of cholesterol-lowering drugs, history of heart attack, and physical activity. Neither total, LDL, nor HDL cholesterol concentrations were associated with risk of aggressive prostate cancer. OR's for a 1 standard deviation (SD) difference were 0.93 (95% CI 0.76-1.14) for total cholesterol (SD=33.7mg/dl), 0.94 (95% CI 0.77-1.15) for LDL cholesterol (SD=30.3mg/dl), and 0.97 (95% CI 0.82-1.16) for HDL cholesterol (SD=12.5mg/dl). Results were similar in analyses excluding the first 2years of follow-up or users of cholesterol-lowering drugs. These results do not support an association between total cholesterol or its subfractions and risk of aggressive prostate cancer.

False-positive screening results in the European randomized study of screening for prostate cancer

BackgroundScreening for prostate cancer (PC) with prostate-specific antigen (PSA) has been shown to decrease mortality, but has adverse effects, such as false-positive (FP) screening results. We describe the frequency of FP results and assess their relation to subsequent screening attendance, test results and prostate cancer risk in a large randomized trial. Materials and methodsWe included data from five centres of the European Randomized Study of Screening for Prostate Cancer, altogether over 61,000 screened men. Men were screened with PSA test at a 2–7year interval depending on the centre; PSA cut-off was 3.0–4.0ng/ml. A positive screen with no histologically confirmed PC in biopsy within 1year was defined as an FP result. ResultsOf the 61,604 men who were screened at least once, 17.8% had one or more FP result(s). Almost 20% of men who participated at all screening rounds had one or more FP result(s). More than half of the men with an FP result had another FP if screened again. Men with FP results had a fourfold risk of PC at subsequent screen (depending on the round, 10.0% versus 2.6–2.7% of men with negative screen, risk ratio 3.8–3.9). The PCs following an FP result were in 92.8% of cases localised and low-grade versus 90.4% following a screen-negative result. ConclusionsOur results show that FP results are common adverse effects in PC screening, as they affect at least one in six screened men. False-positive men are more prone to be diagnosed with PC but are also likely to have consistently high PSA levels.