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Background: Periodontal disease and DNA methylation markers have separately been associated with lung cancer risk. Examining methylation levels at genomic regions previously linked to periodontal disease may provide insights on the link between periodontal disease and lung cancer. Methods: In a nested case-control study drawn from the CLUE II cohort, we measured DNA methylation levels in 208 lung cancer cases and 208 controls. We examined the association between 37 DNA-methylated 5'--C--phosphate--G--3' (CpG) sites at three genomic regions, homeobox 4 (HOXA4), zinc finger protein (ZFP57), and a long noncoding RNA gene located in Chr10 (ENSG00000231601), and lung cancer risk. Results: Statistically significant associations with lung cancer risk were observed for all 14 CpG sites from HOXA4 (OR ranging 1.41-1.62 for 1 SD increase in the DNA methylation level, especially within 15 years) and 1 CpG site on gene ENSG00000231601 (OR = 1.34 for 1 SD increase in the DNA methylation level). Although CpG sites on gene ZFP57 were not associated with lung cancer risk overall, statistically significant inverse associations were noted for six CpG sites when restricting follow-up to 15 years (OR = 0.73-0.77 for 1 SD increase in the DNA methylation level). Conclusions: Key methylation levels associated with periodontal disease are also associated with lung cancer risk. For both HOXA4 and ZFP57, the associations were stronger within 15 years of follow-up, which suggest that, if causal, the impact of methylation is acting late in the natural history of lung cancer. [ABSTRACT FROM AUTHOR]

Background: The MHC class I chain-related protein A (MICA) and protein B (MICB) participate in tumor immunosurveillance and may be important in colorectal cancer, but have not been examined in colorectal cancer development. Methods: sMICA and sMICB blood levels were measured by SomaScan in Visit 2 (1990-92, baseline) and Visit 3 (1993-95) samples in cancer-free participants in the Atherosclerosis Risk in Communities Study. We selected rs1051792, rs1063635, rs2516448, rs3763288, rs1131896, rs2596542, and rs2395029 that were located in or in the vicinity of MICA or MICB and were associated with cancer or autoimmune diseases in published studies. SNPs were genotyped by the Affymetrix Genome-Wide Human SNP Array. We applied linear and Cox proportional hazards regressions to examine the associations of preselected SNPs with sMICA and sMICB levels and colorectal cancer risk (236 colorectal cancers, 8,609 participants) and of sMICA and sMICB levels with colorectal cancer risk (312 colorectal cancers, 10,834 participants). In genetic analyses, estimates adjusted for ancestry markers were meta-analyzed. Results: Rs1051792-A, rs1063635-A, rs2516448-C, rs3763288-A, rs2596542-T, and rs2395029-G were significantly associated with decreased sMICA levels. Rs2395029-G, in the vicinity of MICA and MICB, was also associated with increased sMICB levels. Rs2596542-T was significantly associated with decreased colorectal cancer risk. Lower sMICA levels were associated with lower colorectal cancer risk in males (HR = 0.68; 95% confidence interval, 0.49-0.96) but not in females (Pinteraction = 0.08). Conclusions: Rs2596542-T associated with lower sMICA levels was associated with decreased colorectal cancer risk. Lower sMICA levels were associated with lower colorectal cancer risk in males. Impact: These findings support an importance of immunosurveillance in colorectal cancer. [ABSTRACT FROM AUTHOR]

Background: Evidence suggests that periodontal disease is associated with increased lung cancer risk, but whether periodontal pathogens are explanatory is unknown. We prospectively studied associations of prediagnostic circulating antibodies with oral bacteria and of periodontal bacteria in subgingival plaque with lung cancer. Methods: We included 4,263 cancer-free participants in the Atherosclerosis Risk in Communities study with previously measured serum IgG antibodies to 18 oral bacteria. In 1,287 participants for whom subgingival plaque was collected, counts for 8 periodontal bacteria were previously measured. Incident lung cancers (N = 118) were ascertained through 2015 (median follow-up = 17.5 years). We used Cox regression to estimate multivariable-adjusted associations, including for sums of antibodies to orange (C. rectus, F. nucleatum, P. intermedia, P. micra, and P. nigrescens) and red (P. gingivalis, T. forsythensis, and T. denticola) complex bacteria. Results: Orange complex bacteria antibodies were positively associated with lung cancer [per IQR hazard ratios (HR) = 1.15; 95% confidence intervals (CI), 1.02-1.29], which was stronger in men (HR = 1.27, 95% CI 1.08-1.49), and explained by P. intermedia and P. nigrescens (HR = 1.15; 95% CI, 1.04-1.26). Suggestive positive associations with lung cancer (N = 40) were observed for F. nucleatum, A. actinomycetemcomitans, and P. gingivalis counts. Significant positive associations were found for the count to antibody ratio for P. intermedia and P. gingivalis. Conclusions: We identified positive associations with lung cancer for oral bacteria, especially orange complex that are moderately pathogenic for periodontal disease. Impact: This prospective study supports the need for more research on periodontal bacteria in lung cancer etiology. If associations are supported, this may inform novel lung cancer prevention strategies. [ABSTRACT FROM AUTHOR]

Background: Racial disparities in prostate cancer incidence and mortality rates are considerable. We previously found in the Health Professionals Follow-up Study (HPFS) that African-American men had an 80% higher prostate cancer risk than White men. With 21 additional years of follow-up and four-fold increase in cases, we undertook a contemporary analysis of racial differences in prostate cancer incidence and mortality in HPFS. Methods: For 47,679 men, we estimated HRs and 95% confidence intervals (CI) for the association between race and risk of prostate cancer through 2016 using Cox proportional hazards regression. Multivariable models (mHR) were adjusted for lifestyle, diet, family history, and PSA screening collected on biennial questionnaires. Results: 6,909 prostate cancer cases were diagnosed in White, 89 in African-American, and 90 in Asian-American men. African-Americans had higher prostate cancer incidence (mHR = 1.31; 95% CI, 1.06-1.62) and mortality (mHR = 1.67; 95% CI, 1.00-2.78), and lower PSA screening prevalence than White men. The excess risk was greater in the pre-PSA screening era (HR = 1.68; 95% CI, 1.14-2.48) than the PSA screening era (HR = 1.20; 95% CI, 0.93-1.56). Asian-Americans had lower prostate cancer risk (mHR = 0.74; 95% CI, 0.60-0.92), but similar risk of fatal disease compared with white men. Conclusions: Racial differences in prostate cancer incidence and mortality in HPFS are not fully explained by differences in lifestyle, diet, family history, or PSA screening. Impact: Additional research is necessary to address the disproportionately higher rates of prostate cancer in African-American men. [ABSTRACT FROM AUTHOR]

Background: Evidence for aspirin's chemopreventative properties on colorectal cancer (CRC) is substantial, but its mechanism of action is not well-understood. We combined a proteomic approach with Mendelian randomization (MR) to identify possible new aspirin targets that decrease CRC risk. Methods: Human colorectal adenoma cells (RG/C2) were treated with aspirin (24 hours) and a stable isotope labeling with amino acids in cell culture (SILAC) based proteomics approach identified altered protein expression. Protein quantitative trait loci (pQTLs) from INTERVAL (N = 3,301) and expression QTLs (eQTLs) from the eQTLGen Consortium (N = 31,684) were used as genetic proxies for protein and mRNA expression levels. Two-sample MR of mRNA/protein expression on CRC risk was performed using eQTL/pQTL data combined with CRC genetic summary data from the Colon Cancer Family Registry (CCFR), Colorectal Transdisciplinary (CORECT), Genetics and Epidemiology of Colorectal Cancer (GECCO) consortia and UK Biobank (55,168 cases and 65,160 controls). Results: Altered expression was detected for 125/5886 proteins. Of these, aspirin decreased MCM6, RRM2, and ARFIP2 expression, and MR analysis showed that a standard deviation increase in mRNA/protein expression was associated with increased CRC risk (OR: 1.08, 95% CI, 1.03-1.13; OR: 3.33, 95% CI, 2.46-4.50; and OR: 1.15, 95% CI, 1.02-1.29, respectively). Conclusions: MCM6 and RRM2 are involved in DNA repair whereby reduced expression may lead to increased DNA aberrations and ultimately cancer cell death, whereas ARFIP2 is involved in actin cytoskeletal regulation, indicating a possible role in aspirin's reduction of metastasis. [ABSTRACT FROM AUTHOR]

Inflammation is an emerging risk factor for prostate cancer based largely on evidence from animal models and histopathologic observations. However, findings from patho-epidemiologic studies of intraprostatic inflammation and prostate cancer have been less supportive, with inverse associations observed in many studies of intraprostatic inflammation and prostate cancer diagnosis. Here, we propose collider stratification bias as a potential methodologic explanation for these inverse findings and provide strategies for conducting future etiologic studies of intraprostatic inflammation and prostate cancer. [ABSTRACT FROM AUTHOR]

Background: Physical activity has been associated with longer chronic disease-free life expectancy, but specific cancer types have not been investigated. We examined whether leisure-time moderate-to-vigorous physical activity (LTPA) and television (TV) viewing were associated with life expectancy cancer-free. Methods: We included 14,508 participants without a cancer history from the Atherosclerosis Risk in Communities (ARIC) study. We used multistate survival models to separately examine associations of LTPA (no LTPA,

Background: Black men have worse prostate cancer outcomes following treatment than White men even when accounting for prognostic factors. However, biological explanations for this racial disparity have not been fully identified. We previously showed that more variable telomere lengths among cancer cells and shorter telomere lengths in cancer-associated stromal (CAS) cells individually and together ("telomere biomarker") are associated with prostate cancer-related death in surgically treated men independent of currently used prognostic indicators. Here, we hypothesize that Black-White differences in the telomere biomarker and/or in its components may help explain the racial disparity in prostate cancer outcomes. Methods: Black [higher grade (Gleason =4+3) = 34 and lower grade = 93] and White (higher grade = 34 and lower grade = 89) surgically treated men were frequency matched on age, pathologic stage, and grade. We measured telomere lengths in cancer and CAS cells using a robust telomere-specific FISH assay. Tissue microarray and grade-specific distributional cutoff points without regard to race were evaluated. Results: Among men with higher grade disease, the proportion of Black men (47.1%) with more variable cancer cell telomere lengths was 2.3-times higher (P = 0.02) than that in White men (20.6%). In contrast, among men with lower grade disease, cancer cell telomere length variability did not differ by race. The proportion of men with shorter CAS cell telomeres did not differ by race for either higher or lower grade disease. Conclusions: A greater proportion of Black men with higher grade disease have an adverse prostate cancer cell telomere phenotype than White men with higher grade disease. Impact: Our findings suggest a possible explanation for the racial disparity in prostate cancer outcomes. [ABSTRACT FROM AUTHOR]

Background: Inflammation and focal atrophy are common features adjacent to prostate tumors. Limited evidence exists on whether these features have prognostic significance. Methods: In the Health Professionals Follow-Up Study and Physicians' Health Study, we studied 1,035 men diagnosed with prostate cancer. A genitourinary pathologist centrally reviewed tumor and normal areas of hematoxylin and eosin slides from prostate cancer specimens for the presence of acute and chronic inflammation, and four subtypes of focal atrophy. Cox proportional hazards models adjusted for potential confounders were used to estimate HRs and 95% confidence intervals (CI) for the association of these features with lethal prostate cancer, defined as development of metastatic disease or death during follow-up. Results: During a median of 12 years of follow-up, 153 men developed lethal prostate cancer. A total of 84% of men had histologic evidence of chronic inflammation and 30% had acute inflammation. Both chronic and acute inflammation were inversely associated with lethal prostate cancer in age- and lifestyle-adjusted models. Chronic inflammation remained inversely associated with lethal prostate cancer after additionally adjusting for prognostic clinical features (HR = 0.45; 95% CI, 0.30-0.69 for mild and HR = 0.51; 95% CI, 0.33-0.80 for moderate to severe). None of the atrophic lesions were associated with lethal prostate cancer. Conclusions: Our data suggest that the presence of inflammation, particularly chronic inflammation, in prostate cancer tissue is associated with better prognosis among patients with prostate cancer. Impact: This is the largest prospective cohort study to examine the association between inflammation, focal atrophy, and lethal prostate cancer. [ABSTRACT FROM AUTHOR]

Background: To evaluate the association of liver fibrosis scores with PSA level among U.S. adult men overall and by race/ethnicity. Methods: Data from the National Health and Nutrition Examination Survey (NHANES), 2001-2010, were used. Males ages =40 years without a prostate cancer diagnosis and who had serum PSA, liver enzymes, albumin, and platelet counts measured as part of NHANES protocol were included. Liver fibrosis was measured using three scores: aspartate aminotransferase to platelet ratio index (APRI), fibrosis 4 index (FIB-4), and NAFLD fibrosis score (NFS). We assessed overall and race/ethnicity-stratified geometric mean PSA by fibrosis score using predictive margins by linear regression, and the association of abnormal fibrosis scores (APRI > 1, FIB-4 > 2.67, NFS > 0.676) and elevated PSA (>4 ng/mL) by logistic regression. Results: A total of 6,705 men were included. Abnormal liver fibrosis scores were present in 2.1% (APRI), 3.6% (FIB-4), and 5.6% (NFS). Men with higher fibrosis scores had lower geometric mean PSA (all Ptrend < 0.02). Men with abnormal APRI had a lower odds of PSA > 4 ng/mL [adjusted OR (aOR) = 0.33; 95% confidence interval (CI), 0.11-0.96]. Compared with men with 0 abnormal scores, those with 2 or 3 abnormal fibrosis scores had a lower odds of PSA > 4 ng/mL (aOR = 0.55; 95% CI, 0.33-0.91). The patterns were similar by race/ethnicity. Conclusions: Men of all race/ethnicities with higher liver fibrosis scores had lower serum PSA, and men with advanced fibrosis scores had a lower odds of an elevated PSA. Impact: These findings support further research to inform the likelihood of delay in prostate cancer detection in men with abnormal liver function. [ABSTRACT FROM AUTHOR]

Background: Laboratory and epidemiologic research suggests a protective role of magnesium in colorectal cancer development. We estimated the associations of serum and dietary magnesium with colorectal cancer incidence in the Atherosclerosis Risk in Communities (ARIC) study. Methods: Serum magnesium concentration was measured in blood collected twice (1987-1989 and 1990-1992) and averaged. Dietary magnesium was assessed by food-frequency questionnaire administered twice (1987-1989 and 1993-1995) and averaged. For both dietary and serum magnesium, the averaged measures were categorized into quintiles for analysis. Analyses included 315 colorectal cancer cases among 13,009 participants for serum magnesium (followed for a median of 20.4 years), and 256 cases among 10,971 participants for dietary magnesium (followed for a median of 17.5 years). Cox proportional hazards regression was used to calculate multivariable-adjusted HRs and 95% confidence intervals (CI). Results: Multivariable-adjusted HRs (95% CI) of colorectal cancer for the highest four quintiles compared with the first quintile of serum magnesium were as follows: Q2: 0.70 (0.49-0.99); Q3: 0.68 (0.47-1.00); Q4: 0.87 (0.62-1.21); and Q5: 0.79 (0.57-1.11; Ptrend = 0.04). An inverse association was present in females (HR for Q5 vs. Q1: 0.59, 95% CI: 0.36-0.98, Ptrend = 0.01), but not males (HR for Q5 vs. Q1: 1.10, 95% CI: 0.67-1.79, Ptrend = 0.92; Pinteraction = 0.34). Dietary magnesium was not statistically significantly associated with colorectal cancer risk. Conclusions: Our study found a higher risk of colorectal cancer with lower serum magnesium among females, but not males. Impact: If our findings are confirmed, maintaining adequate serum magnesium levels may be important for colorectal cancer prevention. [ABSTRACT FROM AUTHOR]

Background: Given the recent findings from pooled studies about a potential inverse association between selenium levels and prostate cancer risk, this cross-sectional study aimed to investigate the association between serum selenium and serum concentrations of sex steroid hormones including estradiol in a nationally representative sample of U.S. men to investigate one mechanism by which selenium may influence prostate cancer risk. Methods: The study included 1,420 men ages 20 years or older who participated in the Third National Health and Nutrition Examination Survey between 1988 and 1994. We calculated age/race-ethnicity-adjusted and multivariable-adjusted geometric mean serum concentrations of total and estimated free testosterone and estradiol, androstanediol glucuronide, and sex hormone binding globulin, and compared them across quartiles of serum selenium. Results: Adjusting for age, race/ethnicity, smoking status, serum cotinine, household income, physical activity, alcohol consumption, and percent body fat, mean total estradiol [e.g., Q1, 38.00 pg/mL (95% confidence interval (CI), 36.03-40.08) vs. Q4, 35.29 pg/mL (95% CI, 33.53-37.14); Ptrend = 0.050] and free estradiol [e.g., Q1, 0.96 pg/mL (95% CI, 0.92-1.01) vs. Q4, 0.90 (95% CI, 0.85-0.95); Ptrend = 0.065] concentrations decreased over quartiles of selenium. Stratification by smoking and alcohol consumption, showed that the latter observation was stronger for never smokers (Pinteraction = 0.073) and those with limited alcohol intake (Pinteraction = 0.017). No associations were observed for the other sex steroid hormones studied. Conclusions: Our findings suggests that a possible mechanism by which selenium may be protective for prostate cancer is related to estrogen. Impact: Further studies of longitudinal measurements of serum and toenail selenium in relation to serum measurements of sex steroid hormones are needed. [ABSTRACT FROM AUTHOR]

Background: NSAIDs appear to moderately reduce prostate cancer risk. However, evidence is limited on whether NSAIDs protect against prostate cancer mortality (death from prostate cancer among men without a cancer history) and case fatality (death from prostate cancer among men with prostate cancer), and whether benefits are consistent in white and black men. This study investigated associations of aspirin and non-aspirin (NA) NSAID use with prostate cancer incidence, mortality, and case fatality in a population-based cohort of white and black men. Methods: We included 6,594 men (5,060 white and 1,534 black) from the Atherosclerosis Risk in Communities study without a cancer history at enrollment from 1987 to 1989. NSAID use was assessed at four study visits (1987-1998). Cancer outcomes were ascertained through 2012. Cox proportional hazards regression was used to estimate adjusted HRs, overall and by race. Results: Aspirin use was not associated with prostate cancer incidence. However, aspirin use was inversely associated with prostate cancer mortality [HR, 0.59; 95% confidence interval (CI), 0.36-0.96]. This association was consistent among white and black men and appeared restricted to men using aspirin daily and/or for cardiovascular disease prevention. Aspirin use was inversely associated with case fatality (HR, 0.45; 95% CI, 0.22-0.94). NA-NSAID use was not associated with these endpoints. Conclusions: Aspirin use was inversely associated with prostate cancer mortality and case fatality among white and black men. Impact: If confirmed by additional studies, benefits of aspirin for preventing prostate cancer mortality may need to be factored into risk-benefit calculations of men considering an aspirin regimen. [ABSTRACT FROM AUTHOR]

Background: Research reproducibility is vital for translation of epidemiologic findings. However, repeated studies of the same question may be undertaken without enhancing existing knowledge. To identify settings in which additional research is or is not warranted, we adapted research synthesis metrics to determine number of additional observational studies needed to change the inference from an existing meta-analysis. Methods: The fail-safe number (FSN) estimates number of additional studies of average weight and null effect needed to drive a statistically significant meta-analysis to null (P = 0.05). We used conditional power to determine number of additional studies of average weight and equivalent heterogeneity to achieve 80% power in an updated meta-analysis to detect the observed summary estimate as statistically significant. We applied these metrics to a curated set of 98 meta-analyses on biomarkers and cancer risk. Results: Both metrics were influenced by number of studies, heterogeneity, and summary estimate size in the existing meta-analysis. For the meta-analysis on Helicobacter pylori and gastric cancer with 15 studies [OR = 2.29; 95% confidence interval (CI), 1.71-3.05], FSN was 805 studies, supporting futility of further study. For the meta-analysis on dehydroepiandrosterone sulfate and prostate cancer with 7 studies (OR = 1.29; 95% CI, 0.99-1.69), 5 more studies would be needed for 80% power, suggesting further study could change inferences. Conclusions: Along with traditional assessments, these metrics could be used by stakeholders to decide whether additional studies addressing the same question are needed. Impact: Systematic application of these metrics could lead to more judicious use of resources and acceleration from discovery to population-health impact. [ABSTRACT FROM AUTHOR]

Purpose There has been a marked increase in testosterone prescriptions in the past decade resulting in a growing need to give practicing clinicians proper guidance on the evaluation and management of the testosterone deficient patient. Materials and Methods A systematic review utilized research from the Mayo Clinic Evidence Based Practice Center and additional supplementation by the authors. Evidence-based statements were based on body of evidence strength Grade A, B, or C and were designated as Strong, Moderate, and Conditional Recommendations with additional statements presented in the form of Clinical Principles or Expert Opinions ( table 1 in supplementary unabridged guideline, http://jurology.com/ ). Results This guideline was developed by a multi-disciplinary panel to inform clinicians on the proper assessment of patients with testosterone deficiency and the safe and effective management of men on testosterone therapy. Additional statements were developed to guide the clinician on the appropriate care of patients who are at risk for or have cardiovascular disease or prostate cancer as well as patients who are interested in preserving fertility. Conclusions The care of testosterone deficient patients should focus on accurate assessment of total testosterone levels, symptoms, and signs as well as proper on-treatment monitoring to ensure therapeutic testosterone levels are reached and symptoms are ameliorated. Future longitudinal observational studies and clinical trials of significant duration in this space will improve diagnostic techniques and treatment of men with testosterone deficiency as well as provide more data on the adverse events that may be associated with testosterone therapy. [ABSTRACT FROM AUTHOR]

Background: We describe the expansion of the Atherosclerosis Risk in Communities (ARIC) Study into a cancer cohort. In 1987 to 1989, ARIC recruited 15,792 participants 45 to 64 years old to be sex (55% female), race (27% black), and geographically diverse. ARIC has exceptional data collected during 6 clinical visits and calls every 6 months, repeated biospecimens, and linkage to Medicare claims data. Methods: We established a Cancer Coordinating Center to implement infrastructure activities, convened a Working Group for data use, leveraged ARIC staff and procedures, and developed protocols. We initiated a cancer-specific participant contact, added questions to existing contacts, obtained permission to collect medical records and tissue, abstracted records, linked with state cancer registries, and adjudicated cases and characterizing data. Results: Through 2012, we ascertained and characterized 4,743 incident invasive, first, and subsequent primary cancers among 4,107 participants and 1,660 cancer-related deaths. We generated a total cancer incidence and mortality analytic case file, and analytic case files for bladder, breast, colorectal, liver, lung, pancreas, and prostate cancer incidence, mortality, and case fatality. Adjudication of multiple data sources improved case records and identified cancers not identified via registries. From 2013 onward, we ascertain cases from self-report coupled with medical records. Additional cancer registry linkages are planned. Conclusions: Compared with starting a new cohort, expanding a cardiovascular cohort into ARIC Cancer was an efficient strategy. Our efforts yielded enhanced case files with 25 years of follow-up. Impact: Now that the cancer infrastructure is established, ARIC is contributing its unique features to modern cancer epidemiology research. [ABSTRACT FROM AUTHOR]

Background: We leveraged two trials to test the hypothesis of an inflammation-prostate cancer link prospectively in men without indication for biopsy. Methods: Prostate Cancer Prevention Trial (PCPT) participants who had an end-of-study biopsy performed per protocol that was negative for cancer and who subsequently enrolled in the Selenium and Vitamin E Cancer Prevention Trial (SELECT) were eligible. We selected all 100 cases and sampled 200 frequency-matched controls and used PCPT end-of-study biopsies as "baseline." Five men with PSA > 4 ng/mL at end-of-study biopsy were excluded. Tissue was located for 92 cases and 193 controls. We visually assessed inflammation in benign tissue. We estimated ORs and 95% confidence intervals (CI) using logistic regression adjusting for age and race. Results: Mean time between biopsy and diagnosis was 5.9 years. In men previously in the PCPT placebo arm, 78.1% of cases (N = 41) and 68.2% of controls (N = 85) had at least one baseline biopsy core (∼5 evaluated per man) with inflammation. The odds of prostate cancer (N = 41 cases) appeared to increase with increasing mean percentage of tissue area with inflammation, a trend that was statistically significant for Gleason sum <4+3 disease (N = 31 cases; vs. 0%, >0-<1.8% OR = 1.70, 1.8-<5.0% OR = 2.39, ≥5% OR = 3.31, Ptrend = 0.047). In men previously in the finasteride arm, prevalence of inflammation did not differ between cases (76.5%; N = 51) and controls (75.0%; N = 108). Conclusions: Benign tissue inflammation was positively associated with prostate cancer. Impact: This first prospective study of men without biopsy indication supports the hypothesis that inflammation influences prostate cancer development. [ABSTRACT FROM AUTHOR]

Background: Evidence is mounting that intraprostatic inflammation influences prostate cancer development. Uric acid crystals depositing in the prostate could result in injury and inflammation, increasing prostate cancer risk. Methods: Included were 6,574 men ages 45-64 years who enrolled in the Atherosclerosis Risk in Communities study in 1987 to 1989. We used Cox proportional hazards regression to estimate the association of serum urate concentration alone and to improve accuracy, jointly with a genetic risk score (GRS, N = 4,983) derived from variants predictive of urate concentration, with prostate cancer (N = 813) risk. Results: Serum urate concentration or joint categories of urate concentration and GRS were not associated with prostate cancer risk (Ptrend for quartiles = 0.3). Results were generally similar by race and after excluding users of medications that influence uric acid. Conclusions: Serum urate alone and with a urate-associated GRS were not associated with prostate cancer risk. Impact: It is unlikely that circulating urate concentration influences prostate cancer development. [ABSTRACT FROM AUTHOR]

Background: Serum β-2 microglobulin (B2M), a major histocompatibility complex class I molecule that is a biomarker of kidney filtration and increased cell turnover, is elevated at the time of diagnosis in hematological and some solid cancers. However, serum B2M was not examined prospectively as a marker for cancer risk. We hypothesized that in a population without a prior cancer diagnosis, serum B2M is associated with risk of cancer (n = 2,436), including colorectal (n = 255), lung (n = 298), breast (n = 424), and prostate (n = 524) cancers, and hematological (n = 176) malignancies. Methods: The analytical cohort (n = 12,300) was followed for incident cancers from 1990 through 2006. B2M (range, 0.9-57.8 mg/L) was measured in stored serum collected in 1990-1992. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals for cancer incidence and mortality in relation to quartiles of B2M. Results: Adjusting for age, sex, race, center, education, body mass index, smoking, aspirin, and hormone therapy (in women) and comparing highest to lowest B2M quartiles, HRs were 1.25 (1.06-1.47; Ptrend = 0.002) for total cancer risk and 2.21 (1.32-3.70; Ptrend=0.001) for colorectal cancer risk, with similar HRs for colon and rectal cancers. These associations remained after adjustment for an inflammatory biomarker, C-reactive protein, and after excluding the first three years of follow-up. Significant associations were also observed for mortality from total, lung, and hematological cancers. Conclusions: These findings provide the first evidence that higher serum B2M is associated with increased colorectal cancer risk. Impact: This study supports B2M as a potential biomarker for colorectal cancer risk. [ABSTRACT FROM AUTHOR]

Background: A previous analysis of the placebo arm of the Prostate Cancer Prevention Trial (PCPT) reported 82% overall prevalence of intraprostatic inflammation and identified a link between inflammation and higher-grade prostate cancer and serum PSA. Here, we studied these associations in the PCPT finasteride arm. Methods: Prostate cancer cases (N = 197) detected either on a clinically indicated biopsy or on protocol-directed end-ofstudy biopsy, and frequency-matched controls (N = 248) with no cancer on an end-of-study biopsy were sampled from the finasteride arm. Inflammation in benign prostate tissue was visually assessed using digital images of hematoxylin and eosin-stained sections. Logistic regression was used for statistical analysis. Results: In the finasteride arm, 91.6% of prostate cancer cases and 92.4% of controls had at least one biopsy core with inflammation in benign areas (P < 0.001 for difference compared with placebo arm). Overall, the odds of prostate cancer did not differ by prevalence [OR, 0.90;95%confidence interval (CI), 0.44-1.84] or extent (P trend = 0.68) of inflammation. Inflammation was not associated with higher-grade disease (prevalence: OR, 1.07; 95% CI, 0.43-2.69). Furthermore, mean PSA concentration did not differ by the prevalence or extent of inflammation in either cases or controls. Conclusion: The prevalence of intraprostatic inflammation was higher in the finasteride than placebo arm of the PCPT, with no association with higher-grade prostate cancer. Impact: Finasteride may attenuate the association between inflammation and higher-grade prostate cancer. Moreover, the missing link between intraprostatic inflammation and PSA suggests that finasteride may reduce inflammation-associated PSA elevation. [ABSTRACT FROM AUTHOR]

Purpose Although chronic prostatitis/chronic pelvic pain syndrome is a prevalent urological disorder among men of all ages, its etiology remains unknown. Only a few previous studies have examined associations between lifestyle factors and chronic prostatitis/chronic pelvic pain syndrome, of which most were limited by the cross-sectional study design and lack of control for possible confounders. To address these limitations we performed a cohort study of major lifestyle factors (obesity, smoking and hypertension) and chronic prostatitis/chronic pelvic pain syndrome risk in the HPFS (Health Professionals Follow-up Study), a large ongoing cohort of United States based male health professionals. Materials and Methods The HPFS includes 51,529 men who were 40 to 75 years old at baseline in 1986. At enrollment and every 2 years thereafter participants have completed questionnaires on lifestyle and health conditions. In 2008 participants completed an additional set of questions on recent chronic prostatitis/chronic pelvic pain syndrome pain symptoms modified from the NIH (National Institutes of Health)-CPSI (Chronic Prostatitis Symptom Index) as well as questions on approximate date of symptom onset. The 653 participants with NIH-CPSI pain scores 8 or greater who first experienced symptoms after 1986 were considered incident chronic prostatitis/chronic pelvic pain syndrome cases and the 19,138 who completed chronic prostatitis/chronic pelvic pain syndrome questions but did not report chronic prostatitis/chronic pelvic pain syndrome related pain were considered noncases. Results No associations were observed for baseline body mass index, waist circumference, waist-to-hip ratio, cigarette smoking and hypertension with chronic prostatitis/chronic pelvic pain syndrome risk (each OR ≤1.34). Conclusions In this large cohort study none of the lifestyle factors examined was associated with chronic prostatitis/chronic pelvic pain syndrome risk. As the etiology of chronic prostatitis/chronic pelvic pain syndrome remains unknown, additional prospective studies are needed to elucidate modifiable risk factors for this common condition. [ABSTRACT FROM AUTHOR]

Background: Evidence relating heterocyclic aromatic amines (HCA), associated with high-temperature cooking methods, to prostate cancer risk is inconsistent. Methods: In a large U.S. cohort study, intakes of 2-amino-1- methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-3,8- dimethylimidazo[4,5-f]quinoxaline (MeIQx), and 2-amino- 3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) and a meat-derived mutagenicity (MDM) index were assessed using a cooking method questionnaire administered in 1996. Until 2010, 2,770 prostate cancer cases were observed among 26,030 participants. Results: Intake of PhIP from red meat was statistically significantly associated with total prostate cancer risk (top vs. bottom quintile HR, 1.18; 95% confidence intervals; CI, 1.03-1.35), but not other HCAs (MeIQx, 1.12; 0.98-1.27, PhIP from white meat, 1.08; 0.95-1.22, DiMeIQx, 1.09; 0.97-1.21) or MDM (1.13; 1.00-1.28). For high-grade (Gleason sum 7 with pattern 4+3 and Gleason sum 8-10, n = 483 cases) and advanced cancers (n = 281), we only observed positive associations for PhIP from red meat (top vs. bottom quintile: high grade: HR, 1.44; 95% CI, 1.04-1.98, Ptrend = 0.03; advanced: HR, 1.50; 95% CI, 0.99-2.26; Ptrend = 0.12), but associations for advanced cancers did not reach statistical significance. Observed associations remained similar after adjustment for total, unprocessed, or processed red meat intake. Conclusion: Observed positive associations between PhIP intake from red meat and prostate cancer, particularly high-grade and possibly also advanced prostate cancer, need to be confirmed in other studies. Impact: Results do not provide strong evidence that HCAs increase risk of prostate cancers. [ABSTRACT FROM AUTHOR]

Background: Findings from epidemiologic studies examining associations of serum retinol and carotenoids with prostate cancer risk have been inconsistent. This case-control study nested in the Prostate Cancer Prevention Trial evaluated associations of serum retinol and carotenoids with total, low-, and high-grade prostate cancer risk in a highly screened study population. Methods: We used logistic regression adjusting for age, family history of prostate cancer, race, body mass index, and serum cholesterol to estimate ORs and 95% confidence intervals (CI) of prostate cancer by quartiles of serum retinol and carotenoids, separately in the placebo (975 cases/1,009 frequency-matched controls) and finasteride (708 cases/743 frequency-matched controls) arms of the trial. Results: Serum retinol concentrations were associated with increased risk of total prostate cancer [OR (95% CI) comparing the highest quartile of serum retinol with the lowest: 1.30 (1.00-1.68)] and high-grade prostate cancer [OR (95% CI), 1.74 (1.14-2.68)] in the placebo arm of the trial only. Also in the placebo arm, there was a moderate positive association of a-carotene with risk of total prostate cancer [OR (95%CI), 1.32 (1.01-1.73)]. None of the other carotenoids was associated with prostate cancer risk in the placebo arm. No associations were observed for retinol and carotenoids in the finasteride arm. Conclusion: In the placebo arm of this prospective study, high serum retinol and a-carotene concentrations were associated with increased risk of total and high-grade prostate cancers. Impact: Men with higher levels of serum retinol and a-carotene may be at increased risk for prostate cancer. [ABSTRACT FROM AUTHOR]

The article presents study on the impact of environmental factors on genetic risk of prostate cancer. It mentions discusses the association between susceptibility single nucleotide polymorphism (SNPs) and prostate cancer. It adds that the study suggests that selenium supplements may help in reducing genetic risk of advanced prostate cancer while aspirin, ibuprofen and vegetables may help in reducing genetic risk of nonadvanced prostate cancer.

The article discusses genome-wide association studies (GWAS) that reveals association between single nucleotide polymorphisms (SNPs) and prostate cancer. It mentions the simulation study conducted to quantify the influence of SNP on the Prostate-Specific Antigen (PSA) concentration. It adds the calculation of mean betas from the replicate cohorts and prevalence of carrying minor allele.

The article presents a study which analyses risks associated with colorectal cancers and adenomas with reference to John Cunningham virus (JCV) T-antigen. Topics discussed under study include role of JCV in colorectal carcinogenesis, role of seroreactivity to JCV T-antigen oncoprotein in colorectal cancer, and identification of colorectal cancer cases by linkage to population-based cancer registries.

The article presents research that aimed to evaluate the association between peripheral-cytokine concentrations and prostate cancer. The research conducted a case-control study on incidence of prostate cancer on in the CLUE II cohort study. The research showed that men with circulating TH1 cytokine profile and higher interleukin-6 (IL6) are supposed to have a lower risk of prostate cancer.

Purpose Recurrent prostate cancer remains a major problem. Staging, grading and prostate specific antigen level at surgery are helpful but still imperfect predictors of recurrence. For this reason there is an imperative need for additional biomarkers that add to the prediction of currently used prognostic factors. Materials and Methods We evaluated the extent of promoter methylation of genes previously reported as aberrantly methylated in prostate cancer ( AIM1 , APC , CCND2 , GPX3 , GSTP1 , MCAM , RARβ2 , SSBP2 and TIMP3 ) by quantitative fluorogenic methylation-specific polymerase chain reaction. We used cancer tissue from a nested case-control study of 452 patients surgically treated for prostate cancer. Recurrence cases and controls were compared and the association between methylation extent and recurrence risk was estimated by logistic regression adjusting for patient age at prostatectomy, prostatectomy year, stage, grade, surgical margins and preprostatectomy prostate specific antigen. All statistical tests were 2-sided with p ≤0.05 considered statistically significant. Results The extent of GSTP1 methylation was higher in patients with recurrence than in controls (p = 0.01), especially patients with early disease, ie organ confined or limited extraprostatic extension (p = 0.001). After multivariate adjustment GSTP1 promoter methylation at or above the median was associated with an increased risk of recurrence, including in men with early disease (each p = 0.05). Conclusions Greater GSTP1 promoter methylation in cancer tissue was independently associated with the risk of recurrence in patients with early prostate cancer. This suggests that GSTP1 promoter methylation may be a potential tissue based recurrence marker. [ABSTRACT FROM AUTHOR]

Objective This study aimed to quantify functional status (FS) trajectories pre- and post-diagnosis of cancer, FS trajectories among cancer-free individuals, and factors affecting FS. Materials and Methods Self-reported FS, scored from 0 (worst) to 100 (best), of Atherosclerosis Risk in Communities (ARIC) Study cohort participants diagnosed with incident cancer (lung ( N = 303), breast ( N = 374), prostate ( N = 529), colorectal ( N = 228)), and cancer-free participants ( N = 11,155) over 15 years was examined. FS was evaluated in two ways: 1) until death or follow-up year 15 (Model 1) and 2) same as survivorship model except that a FS value of zero was used for assessments after death to follow-up year 15 (Model 2). Mean FS at discrete time points were used to generate FS trajectories. Differences in repeated measures of FS were assessed using linear growth models. Results Within one year after diagnosis, FS scores declined compared to the cancer-free group, except for prostate cancer. FS continued to decline beyond one year after lung or colorectal cancer diagnosis. FS was lower in all cancer groups, except prostate, compared to the cancer-free group (Model 1: lung − 4.76, breast − 2.28, colorectal − 2.55; Model 2: lung − 2.36, breast − 2.46, colorectal − 2.31). Predictors of decreased FS score independent of cancer diagnosis included low education, comorbidities, obesity, smoking, lack of health insurance, and age. Conclusion FS in all incident cancer groups declined during the first year post-diagnosis, which could be due to intensive treatments. Targeting factors related to FS declines could improve health outcomes for patients with cancer. [ABSTRACT FROM AUTHOR]

Purpose Prospective cohort studies support the hypothesis that statin drug users have a lower risk of aggressive prostate cancer. Whether statin drug use influences the risk of screen detected disease is less clear, possibly because of complex detection biases. Thus, we investigated this association in a setting in which men had low baseline serum prostate specific antigen concentration and were screened annually. Materials and Methods We performed a cohort study of 9,457 men 55 years old or older at randomization to the placebo arm of PCPT (Prostate Cancer Prevention Trial). The men reported new use of medications quarterly. We estimated the multivariable adjusted HR of prostate cancer (574 cases in 62,192 person-years) for statin drug use and duration of use during the trial using Cox proportional hazards regression. Results During 7 years of followup statin drug use during the trial was not associated with the risk of total prostate cancer (HR 1.03, 95% CI 0.82-1.30), or lower grade (HR 0.96, 95% CI 0.71-1.29) or higher grade (HR 1.27, 95% CI 0.85-1.90) prostate cancer. Duration of use during followup was also not associated with the risk of total, or lower or higher grade disease (p trend = 0.7, 0.5 and 0.2, respectively). Conclusions These prospective results do not support the hypothesis that statin drugs protect against prostate cancer in the setting of regular prostate cancer screening. [ABSTRACT FROM AUTHOR]

The article discusses the study that determined the association of chronic inflammation in benign prostate tissue with prostate cancer, based on samples from the placebo arm of the Prostate Cancer Prevention Trial. Findings discussed include positive association of chronic inflammation in benign prostate tissue to prostate cancer, especially high grade, and higher odds of prostate cancer for men who has at least one biopsy core with inflammation compared to men with no cores with inflammation.

Purpose: We prospectively evaluated the association between adiposity and the risk of lower urinary tract symptoms incidence and progression in the Health Professionals Followup Study (HPFS). Materials and Methods: At baseline participants reported current height and weight, and weight at age 21 years. A year later they reported waist and hip circumferences, and every 2 years thereafter they reported weight. Participants periodically completed the International Prostate Symptom Score (I-PSS) and reported surgery or medication use for lower urinary tract symptoms. We used Cox proportional hazards regression to estimate the multivariable adjusted association between adiposity and lower urinary tract symptoms incidence and progression. The incidence analytical cohort of 18,055 men had no lower urinary tract symptoms at baseline. A total of 6,461 men entered the progression analytical cohort when they first experienced lower urinary tract symptoms. Results: The risk of lower urinary tract symptoms in 4,088 cases increased with increasing body mass index (35 kg/m2 or greater vs 23 to less than 25 HR 1.61, 95% CI 1.31–1.99), waist circumference (greater than 42 inches vs 33 or less HR 1.39, 95% CI 1.19–1.63) and weight gain since age 21 years (50 pounds or greater vs stable weight HR 1.31, 95% CI 1.17–1.46, each p trend <0.0001). The risk of lower urinary tract symptom progression in 1,691 cases increased with body mass index (35 kg/m2 or greater vs 23 to less than 25 HR 1.44, 95% CI 1.04–2.00, p trend <0.0001), weight gain since age 21 years (50 pounds or greater vs stable weight HR 1.35, 95% CI 1.14–1.60, p trend <0.0001) and waist circumference (greater than 42 inches vs 33 or less HR 1.32, 95% CI 0.95–1.85, p trend 0.005). Conclusions: Men with higher total and abdominal adiposity and those who gained weight were more likely to have lower urinary tract symptoms develop or progress. Our findings support the notion that obesity may be an important target for lower urinary tract symptom prevention and intervention. [Copyright &y& Elsevier]