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1.
Cancer Epidemiol Biomarkers Prev ; 30(2): 255-259, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33547143

RESUMO

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.

2.
Nutr Cancer ; : 1-8, 2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33511883

RESUMO

Non-supplemental carotenoids and retinol may potentiate antioxidant and anti-inflammatory mechanisms. Chronic intraprostatic inflammation is linked to prostate carcinogenesis. We investigated the association of circulating carotenoids and retinol with intraprostatic inflammation in benign tissue. We included 235 men from the Prostate Cancer Prevention Trial placebo arm who had a negative end-of-study biopsy, most (92.8%) done without clinical indication. α-carotene, ß-carotene, ß-cryptoxanthin, lycopene, and retinol were assessed by high-performance liquid chromatography using pooled year 1 and 4 serum. Presence and extent of intraprostatic inflammation in benign tissue was assessed in 3 (of 6-10) biopsy cores. Logistic (any core with inflammation vs none) and polytomous logistic (some or all cores with inflammation vs none) regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) of intraprostatic inflammation by concentration tertile adjusting for age, race, prostate cancer family history, and serum cholesterol. None of the carotenoids or retinol was associated with intraprostatic inflammation, except ß-cryptoxanthin, which appeared to be positively associated with any core with inflammation [vs none, T2: OR (95% CI) = 2.67 (1.19, 5.99); T3: 1.80 (0.84, 3.82), P-trend = 0.12]. These findings suggest that common circulating carotenoids and retinol are not useful dietary intervention targets for preventing prostate cancer via modulating intraprostatic inflammation.

3.
Eur Urol ; 2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33257031

RESUMO

BACKGROUND: Single nucleotide polymorphism-based genetic risk score (GRS) has been developed and validated for prostate cancer (PCa) risk assessment. As GRS is population standardized, its value can be interpreted as a relative risk to the general population. OBJECTIVE: To compare the performance of GRS with two guideline-recommended inherited risk measures, family history (FH) and rare pathogenic mutations (RPMs), for predicting PCa incidence and mortality. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort was derived from the UK Biobank where 208 685 PCa diagnosis-free participants at recruitment were followed via the UK cancer and death registries. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Rate ratios (RRs) of PCa incidence and mortality for FH (positive vs negative), RPMs (carriers vs noncarriers), and GRS (top vs bottom quartile) were measured. RESULTS AND LIMITATIONS: After a median follow-up of 9.67 yr, 6890 incident PCa cases (419 died of PCa) were identified. Each of the three measures was significantly associated with PCa incidence in univariate analyses; RR (95 % confidence interval [CI]) values were 1.88 (1.75-2.01) for FH, 2.89 (1.89-4.25) for RPMs, and 1.97(1.87-2.07) for GRS (all p < 0.001). The associations were independent in multivariable analyses. While FH and RPMs identified 11 % of men at higher PCa risk, addition of GRS identified an additional 22 % of men at higher PCa risk, and increases in C-statistic from 0.58 to 0.67 for differentiating incidence (p < 0.001) and from 0.65 to 0.71 for differentiating mortality (p = 0.002). Limitations were a small number of minority patients and short mortality follow-up. CONCLUSIONS: This population-based prospective study suggests that GRS complements two guideline-recommended inherited risk measures (FH and RPMs) for stratifying the risk of PCa incidence and mortality. PATIENT SUMMARY: In a large population-based prostate cancer (PCa) prospective study derived from UK Biobank, genetic risk score (GRS) complements two guideline-recommended inherited risk measures (family history and rare pathogenic mutations) in predicting PCa incidence and mortality. These results provide critical data for including GRS in PCa risk assessment.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33318029

RESUMO

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. IMPACT: Our approach has shown how laboratory experiments and population-based approaches can combine to identify aspirin-targeted proteins possibly affecting CRC risk.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33355185

RESUMO

In our prior studies, obesity was associated with shorter telomeres in prostate cancer-associated stromal (CAS) cells, and shorter CAS telomeres were associated with an increased risk of prostate cancer death. To determine whether the association between obesity and shorter CAS telomeres is replicable, we conducted a pooled analysis of 790 men who were surgically treated for prostate cancer, whose tissue samples were arrayed on five tissue microarray (TMA) sets. Telomere signal was measured using a quantitative telomere-specific FISH assay and normalized to 4',6-diamidino-2-phenylindole for 351 CAS cells (mean) per man; men were assigned their median value. Weight and height at surgery, collected via questionnaire or medical record, were used to calculate body mass index (BMI; kg/m2) and categorize men as normal (<25), overweight (25 ≤ BMI < 30), or obese (≥30). Analyses were stratified by grade and stage. Men were divided into tertiles of TMA- (overall) or TMA- and disease aggressiveness- (stratified) specific distributions; short CAS telomere status was defined by the bottom two tertiles. We used generalized linear mixed models to estimate the association between obesity and short CAS telomeres, adjusting for age, race, TMA set, pathologic stage, and grade. Obesity was not associated with short CAS telomeres overall, or among men with nonaggressive disease. Among men with aggressive disease (Gleason≥4+3 and stage>T2), obese men had a 3-fold increased odds of short CAS telomeres (OR: 3.06; 95% confidence interval: 1.07-8.75; P trend = 0.045) when compared with normal weight men. Telomere shortening in prostate stromal cells may be one mechanism through which lifestyle influences lethal prostate carcinogenesis. PREVENTION RELEVANCE: This study investigates a potential mechanism underlying the association between obesity and prostate cancer death. Among men with aggressive prostate cancer, obesity was associated with shorter telomeres prostate cancer associated stromal cells, and shorter CAS telomeres have been associated with an increased risk of prostate cancer death.

7.
Int J Cancer ; 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33038280

RESUMO

Obesity is considered a chronic inflammatory state characterized by continued secretion of adipokines and cytokines. Experimental and epidemiological evidence indicates that circulating adipokines may be associated with the development of obesity-related cancers, but it is unclear if these associations are causal or confounded. We examined potential causal associations of specific adipokines (adiponectin, leptin, soluble leptin receptor [sOB-R] and plasminogen activator inhibitor-1 [PAI-1]) with five obesity-related cancers (colorectal, pancreatic, renal cell carcinoma [RCC], ovarian and endometrial) using Mendelian randomization (MR) methods. We used summary-level data from large genetic consortia for 114 530 cancer cases and 245 284 controls. We constructed genetic instruments using 18 genetic variants for adiponectin, 2 for leptin and 4 for both sOB-R and PAI-1 (P value for inclusion<5 × 10-8 ). Causal estimates were obtained using two-sample MR methods. In the inverse-variance weighted models, we found an inverse association between adiponectin and risk of colorectal cancer (odds ratio per 1 µg/mL increment in adiponectin concentration: 0.90 [95% confidence interval = 0.84-0.97]; P = .01); but, evidence of horizontal pleiotropy was detected and the association was not present when this was taken into consideration. No association was found for adiponectin and risks of pancreatic cancer, RCC, ovarian cancer and endometrial cancer. Leptin, sOB-R and PAI-1 were also similarly unrelated to risk of obesity-related cancers. Despite the large sample size, our MR analyses do not support causal effects of circulating adiponectin, leptin, sOB-R and PAI-1 concentrations on the development of five obesity-related cancers.

8.
J Natl Cancer Inst ; 2020 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-33010161

RESUMO

BACKGROUND: In the era of widespread prostate-specific antigen testing, it is important to focus etiologic research on the outcome of aggressive prostate cancer, but studies have defined this outcome differently. We aimed to develop an evidence-based consensus definition of aggressive prostate cancer using clinical features at diagnosis for etiologic epidemiologic research. METHODS: Among prostate cancer cases diagnosed in 2007 in the U.S. SEER-18 database with follow-up through 2017, we compared the performance of categorizations of aggressive prostate cancer in discriminating fatal prostate cancer within 10 years of diagnosis, placing the most emphasis on sensitivity and positive predictive value (PPV). RESULTS: In our case population (n = 55,900), 3,073 men died of prostate cancer within 10 years. Among 12 definitions that included TNM stage and Gleason score, sensitivities ranged from 0.64 to 0.89 and PPVs ranged from 0.09 to 0.23. We propose defining aggressive prostate cancer as diagnosis of stage T4 or N1 or M1 or Gleason score ≥8 prostate cancer, as this definition had one of the higher PPVs (0.23, 95% confidence interval [CI] 0.22-0.24) and reasonable sensitivity (0.66, 95% CI 0.64-0.67) for prostate cancer death within 10 years. Results were similar across sensitivity analyses. CONCLUSIONS: We recommend that etiologic epidemiologic studies of prostate cancer report results for this definition of aggressive prostate cancer. We also recommend that studies separately report results for advanced stage (T4 or N1 or M1), high grade (Gleason score ≥8), and fatal prostate cancer. Use of this comprehensive set of endpoints will facilitate comparison of results from different studies and help elucidate prostate cancer etiology.

9.
Prev Chronic Dis ; 17: E129, 2020 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-33059794

RESUMO

INTRODUCTION: Each US state, territory, and tribe/tribal organization is supported by the Centers for Disease Control and Prevention to develop and implement a comprehensive cancer control (CCC) plan. The objective of this study was to inform areas for improvement of those plans. METHODS: To show how CCC plans can be improved, we used the example of breast cancer, which has a long public health history and an established, broad spectrum of prevention and control activities. We evaluated the inclusion of evidence-based breast cancer prevention topics as provided by guidelines from the Centers for Disease Control and Prevention (CDC) and recommendations of the US Preventive Services Task Force (USPSTF) in each state's CCC plan. From January through March 2019, we downloaded CCC plans from each state and the District of Columbia and abstracted and quantified the content of plans for 1) discussion of data on breast cancer mortality, breast cancer incidence, uptake of mammography; 2) statement of objective to reduce the burden of breast cancer; and 3) review of CDC guidelines and USPSTF recommendations. RESULTS: The discussion of breast cancer-relevant topics and specification of objectives was incomplete. Of 51 plans, data on breast cancer mortality and incidence and uptake of mammography were reported in 53% (n = 27) to 76% (n = 39) of plans. CDC and USPSTF recommendations for breast cancer-specific interventions were discussed in only 6% (n = 3) to 37% (n = 19) of plans. Discussion of general cancer prevention topics relevant to breast cancer ranged from 10% (n = 5) to 61% (n = 31) of plans. CONCLUSION: Our findings inform areas for quality improvement of state CCC plans and may contribute to other areas of public health planning.

10.
Cancer Epidemiol Biomarkers Prev ; 29(12): 2617-2625, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32978174

RESUMO

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,

11.
Liver Int ; 2020 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-32860311

RESUMO

BACKGROUND & AIMS: This study aimed to analyse the association of sex hormone levels with liver enzyme levels and non-alcoholic fatty liver disease (NAFLD) in a nationally representative sample of men. METHODS: 919 men from the US National Health and Nutrition Examination Study (NHANES) III were included in this cross-sectional analysis of data from 1988-1991. We used existing data on serum total and free testosterone, total and free estradiol, androstanediol glucuronide (AAG), sex steroid binding globulin (SHBG), and estimated their associations with aspartate aminotransferase (AST), and alanine aminotransferase (ALT) and NAFLD, as determined using ultrasound, after adjusting for possible confounders including age, race, smoking, alcohol, physical activity, waist circumference and steroid hormones. RESULTS: Lower total testosterone and higher free estradiol were associated with higher odds of NAFLD after adjusting for confounders including the other sex hormones. Lower total testosterone was associated with higher odds of elevated AST, but not ALT. Free testosterone, total estradiol, SHBG and AAG were not associated with NAFLD or liver enzymes. CONCLUSIONS: This study supports an inverse association between total testosterone concentration and NAFLD in men independent of other sex hormones (SHBG, AAG, estradiol) and known risk factors such as obesity, age and lifestyle. Exploration of whether total testosterone might be a non-invasive marker for NAFLD diagnosis is warranted.

12.
Am J Hum Genet ; 107(3): 432-444, 2020 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-32758450

RESUMO

Accurate colorectal cancer (CRC) risk prediction models are critical for identifying individuals at low and high risk of developing CRC, as they can then be offered targeted screening and interventions to address their risks of developing disease (if they are in a high-risk group) and avoid unnecessary screening and interventions (if they are in a low-risk group). As it is likely that thousands of genetic variants contribute to CRC risk, it is clinically important to investigate whether these genetic variants can be used jointly for CRC risk prediction. In this paper, we derived and compared different approaches to generating predictive polygenic risk scores (PRS) from genome-wide association studies (GWASs) including 55,105 CRC-affected case subjects and 65,079 control subjects of European ancestry. We built the PRS in three ways, using (1) 140 previously identified and validated CRC loci; (2) SNP selection based on linkage disequilibrium (LD) clumping followed by machine-learning approaches; and (3) LDpred, a Bayesian approach for genome-wide risk prediction. We tested the PRS in an independent cohort of 101,987 individuals with 1,699 CRC-affected case subjects. The discriminatory accuracy, calculated by the age- and sex-adjusted area under the receiver operating characteristics curve (AUC), was highest for the LDpred-derived PRS (AUC = 0.654) including nearly 1.2 M genetic variants (the proportion of causal genetic variants for CRC assumed to be 0.003), whereas the PRS of the 140 known variants identified from GWASs had the lowest AUC (AUC = 0.629). Based on the LDpred-derived PRS, we are able to identify 30% of individuals without a family history as having risk for CRC similar to those with a family history of CRC, whereas the PRS based on known GWAS variants identified only top 10% as having a similar relative risk. About 90% of these individuals have no family history and would have been considered average risk under current screening guidelines, but might benefit from earlier screening. The developed PRS offers a way for risk-stratified CRC screening and other targeted interventions.


Assuntos
Neoplasias Colorretais/epidemiologia , Predisposição Genética para Doença , Genoma Humano/genética , Medição de Risco , Idoso , Grupo com Ancestrais do Continente Asiático/genética , Teorema de Bayes , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Herança Multifatorial/genética , Polimorfismo de Nucleotídeo Único/genética , Fatores de Risco
13.
Cancer Res ; 80(18): 4004-4013, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32641412

RESUMO

Registry-based epidemiologic studies suggest associations between chronic inflammatory intestinal diseases and pancreatic ductal adenocarcinoma (PDAC). As genetic susceptibility contributes to a large proportion of chronic inflammatory intestinal diseases, we hypothesize that the genomic regions surrounding established genome-wide associated variants for these chronic inflammatory diseases are associated with PDAC. We examined the association between PDAC and genomic regions (±500 kb) surrounding established common susceptibility variants for ulcerative colitis, Crohn's disease, inflammatory bowel disease, celiac disease, chronic pancreatitis, and primary sclerosing cholangitis. We analyzed summary statistics from genome-wide association studies data for 8,384 cases and 11,955 controls of European descent from two large consortium studies using the summary data-based adaptive rank truncated product method to examine the overall association of combined genomic regions for each inflammatory disease group. Combined genomic susceptibility regions for ulcerative colitis, Crohn disease, inflammatory bowel disease, and chronic pancreatitis were associated with PDAC at P values < 0.05 (0.0040, 0.0057, 0.011, and 3.4 × 10-6, respectively). After excluding the 20 PDAC susceptibility regions (±500 kb) previously identified by GWAS, the genomic regions for ulcerative colitis, Crohn disease, and inflammatory bowel disease remained associated with PDAC (P = 0.0029, 0.0057, and 0.0098, respectively). Genomic regions for celiac disease (P = 0.22) and primary sclerosing cholangitis (P = 0.078) were not associated with PDAC. Our results support the hypothesis that genomic regions surrounding variants associated with inflammatory intestinal diseases, particularly, ulcerative colitis, Crohn disease, inflammatory bowel disease, and chronic pancreatitis are associated with PDAC. SIGNIFICANCE: The joint effects of common variants in genomic regions containing susceptibility loci for inflammatory bowel disease and chronic pancreatitis are associated with PDAC and may provide insights to understanding pancreatic cancer etiology.

14.
Cancer Causes Control ; 31(9): 851-860, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32666408

RESUMO

PURPOSE: Prostate cancer burden is disproportionate by race. Black men have the highest incidence and mortality rates. Rates for Hispanic men are significantly lower than for non-Hispanic Whites. Whether differences in prevalences of modifiable risk and protective factors for prostate cancer may explain these racial/ethnic differences remains unclear. METHODS: We used data from the National Health and Nutrition Examination Surveys (NHANES), which are cross-sectional and nationally representative. We selected factors known or suspected to be associated with prostate cancer and calculated risk scores combining key factors. Age-adjusted means and proportions were calculated for each factor and risk score by race/ethnicity. We estimated odds ratios (OR) using polytomous logistic regression. RESULTS: Prevalences of most factors are statistically significantly differed by race/ethnicity. In NHANES III, the prevalence of high risk score (i.e., > 25th percentile for all participants) was lower for all groups (non-Hispanic Black = 59.4%, non-US-born Mexican American = 51.4%, US-born Mexican American = 61.4%) vs. non-Hispanic White men (76.4%). Similar findings were observed for the fatal weighted risk score and for continuous NHANES. CONCLUSIONS: Our findings from this nationally representative study suggest that a combination of multiple risk and protective factors may help to explain the lower rates of prostate cancer in Mexican Americans. However, variation in these factors did not explain the higher risk of prostate cancer in non-Hispanic Black men. No one lifestyle change can reduce prostate cancer equally across all racial/ethnic groups, and modifiable factors may not explain the increased risk in black men at all. Secondary prevention strategies may provide the most benefit for black men.


Assuntos
Afro-Americanos/estatística & dados numéricos , Grupo com Ancestrais do Continente Europeu/estatística & dados numéricos , Americanos Mexicanos/estatística & dados numéricos , Neoplasias da Próstata/etnologia , Neoplasias da Próstata/epidemiologia , Adulto , Estudos Transversais , Humanos , Incidência , Estilo de Vida , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Razão de Chances , Prevalência , Neoplasias da Próstata/mortalidade , Fatores de Proteção , Estados Unidos/epidemiologia
15.
Artigo em Inglês | MEDLINE | ID: mdl-32520772

RESUMO

PURPOSE: Maryland historically had a high cancer burden, which prompted the implementation of aggressive cancer control strategies. We examined the status of cancer in Maryland and work under the current and previous editions of the MD Comprehensive Cancer Control Plan. METHODS: We examined the prevalence of cancer mortality, cancer incidence, and cancer-related behaviors in Maryland and the United States from 1985 to 2015 using publicly available data in the US Cancer Control PLANET, CDC WONDER, and Behavioral Risk Factor Surveillance System portals. We estimated the average annual cancer deaths avoided by triangulation. RESULTS: In 1983-1987, Maryland had the highest age-adjusted cancer mortality rate of all 50 states, second only to Washington, District of Columbia. Today (2011-2015), Maryland's age-adjusted cancer mortality rate ranks 31st. Overall cancer mortality rates have declined 1.9% annually from 1990 to 2015, avoiding nearly 60 000 deaths over 3 decades. While the prevalence of healthy cancer-related behaviors in Maryland was qualitatively similar or higher than that of the United States in 2015, Maryland's 5-year (2011-2015) cancer incidence rate was significantly greater than that of the United States. CONCLUSIONS: Maryland's 30-year cancer mortality declines have outpaced other states. However, a reduction in mortality while incidence rates remain high indicates a need for enhanced focus on primary prevention.

16.
Prostate ; 80(11): 895-905, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32506665

RESUMO

BACKGROUND: Intraprostatic inflammation is an emerging prostate cancer risk factor. Estrogens are pro-inflammatory while androgens are anti-inflammatory. Thus, we investigated whether serum sex steroid hormone concentrations are associated with intraprostatic inflammation to inform mechanistic links among hormones, inflammation, and prostate cancer. METHODS: We conducted a cross-sectional study among 247 men in the placebo arm of the Prostate Cancer Prevention Trial who had a negative end-of-study biopsy, most (92.7%) performed without clinical indication per trial protocol. Serum estradiol, estrone, and testosterone were previously measured by immunoassay in pooled baseline and Year 3 serum. Free estradiol and free testosterone were calculated. Inflammation was visually assessed (median of three prostate biopsy cores per man). Polytomous or logistic regression was used to estimate the odds ratio (OR) and 95% confidence interval (CI) of some or all cores inflamed (both vs none) or any core inflamed (vs none) by hormone tertile, adjusting for age, race, and family history. We evaluated effect modification by waist circumference and body mass index (BMI). RESULTS: In all, 51.4% had some and 26.3% had all cores inflamed. Free (P-trend = .11) but not total estradiol was suggestively inversely associated with all cores inflamed. In men with waist circumference greater than or equal to 102 cm (P-trend = .021) and BMI ≥ 27.09 kg/m2 (P-trend = .0037) free estradiol was inversely associated with any core inflamed. Estrone was inversely associated with all cores inflamed (T3: OR = 0.36, 95% CI 0.14-0.95, P-trend = .036). Total (T3: OR = 1.91, 95% CI 0.91-4.02, P-trend = .11) and free (T3: OR = 2.19, 95% CI 1.01-4.74, P-trend = .05) testosterone were positively associated with any core inflamed, especially free testosterone in men with waist circumference less than 102 cm (T3: OR = 3.51, 95% CI 1.03-12.11, P-trend = .05). CONCLUSIONS: In this first study in men without prostate cancer and irrespective of clinical indication for biopsy, contrary to the hypothesis, circulating estrogens appeared to be inversely associated, especially in heavy men, whereas androgens appeared to be positively associated with intraprostatic inflammation.


Assuntos
Hormônios Esteroides Gonadais/sangue , Prostatite/sangue , Idoso , Biópsia , Peso Corporal , Estudos Transversais , Humanos , Masculino , Pessoa de Meia-Idade , Placebos , Neoplasias da Próstata/prevenção & controle , Prostatite/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto
17.
PLoS One ; 15(6): e0234391, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32525914

RESUMO

BACKGROUND: Pathological and clinical stage are associated with prostate cancer-specific survival after prostatectomy. With PSA screening, the post-surgery prognostic utility of clinical stage is debatable in studies seeking to identify new biomarkers. Few studies have investigated clinical stage and lethal prostate cancer association after accounting for pathological stage. We hypothesize that clinical stage provides prognostic information beyond pathological stage in the PSA era. METHODS: Cox regression models tested associations between clinical and pathological stage and lethal prostate cancer among 3,064 participants from the Health Professionals Follow-Up Study and Physicians' Health Study (HPFS/PHS) who underwent prostatectomy. Likelihood ratio tests and c-statistics were used to assess the models' prognostic utility. Equivalent analyses were performed in 16,134 men who underwent prostatectomy at Johns Hopkins. RESULTS: Independently, clinical and pathological stage were associated (p<0.0001 for both) with rate of lethal prostate cancer in HPFS/PHS. The model with clinical and pathological stage fit significantly better than the model with only pathological stage in all men (p = 0.01) and in men diagnosed during the PSA era (p = 0.04). The mutually adjusted model also improved discriminatory ability. In the Johns Hopkins cohort, the model with clinical and pathological stage improved discriminatory ability and fit significantly better overall (p<0.0001) and in the PSA era (p<0.0001). CONCLUSIONS: Despite stage migration resulting from widespread PSA screening, clinical stage remains associated with progression to lethal prostate cancer independent of pathological stage. Future studies evaluating associations between new factors and poor outcome following prostatectomy should consider including both clinical and pathological stages since the data is already available.


Assuntos
Calicreínas/sangue , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Prostatectomia , Neoplasias da Próstata/cirurgia , Estados Unidos
18.
Cancer Prev Res (Phila) ; 13(10): 853-862, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32581009

RESUMO

Aspirin and statin use may lower the risk of advanced/fatal prostate cancer, possibly by reducing intraprostatic inflammation. To test this hypothesis, we investigated the association of aspirin and statin use with the presence and extent of intraprostatic inflammation, and the abundance of specific immune cell types, in benign prostate tissue from a subset of men from the placebo arm of the Prostate Cancer Prevention Trial. Men were classified as aspirin or statin users if they reported use at baseline or during the 7-year trial. Presence and extent of inflammation were assessed, and markers of specific immune cell types (CD4, CD8, FoxP3, CD68, and c-KIT) were scored, in slides from end-of-study prostate biopsies taken irrespective of clinical indication, per trial protocol. Logistic regression was used to estimate associations between medication use and inflammation measures, adjusted for potential confounders. Of 357 men included, 61% reported aspirin use and 32% reported statin use. Prevalence and extent of inflammation were not associated with medication use. However, aspirin users were more likely to have low FoxP3, a T regulatory cell marker [OR, 5.60; 95% confidence interval (CI), 1.16-27.07], and statin users were more likely to have low CD68, a macrophage marker (OR, 1.63; 95% CI, 0.81-3.27). If confirmed, these results suggest that these medications may alter the immune milieu of the prostate, which could potentially mediate effects of these medications on advanced/fatal prostate cancer risk.

19.
Bone Joint Res ; 9(3): 139-145, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32435466

RESUMO

Aims: To examine the relationship of sex steroid hormones with osteopenia in a nationally representative sample of men in the USA. Methods: Data on bone mineral density (BMD), serum sex hormones, dairy consumption, smoking status, and body composition were available for 806 adult male participants of the cross-sectional National Health and Nutrition Examination Survey (NHANES, 1999-2004). We estimated associations between quartiles of total and estimated free oestradiol (E2) and testosterone (T) and osteopenia (defined as 1 to 2.5 SD below the mean BMD for healthy 20- to 29-year-old men) by applying sampling weights and using multivariate-adjusted logistic regression. We then estimated the association between serum hormone concentrations and osteopenia by percentage of body fat, frequency of dairy intake, cigarette smoking status, age, and race/ethnicity. Results: Men in the lowest quartile of total E2 concentrations (< 21.52 pg/ml) had greater odds of osteopenia compared with men in the highest quartile (odds ratio (OR) 2.29, 95% confidence interval (CI) 1.11 to 4.73; p-trend = 0.030). Total and free T were not associated with osteopenia. Low total E2 concentrations were associated with greater odds of osteopenia among non-daily dairy consumers (p-trend = 0.046), current or former smokers (p-trend = 0.032), and younger men (p-trend = 0.031). No differences were observed by race/ethnicity and obesity. Conclusion: In this nationally representative study of the USA, men with lower total E2 were more likely to have osteopenia, which was particularly evident among younger men, men with less-than-daily dairy consumption, and current or former smokers.Cite this article: Bone Joint Res. 2020;9(3):139-145.

20.
J Gen Intern Med ; 35(8): 2281-2288, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32347424

RESUMO

BACKGROUND: Lower urinary tract symptoms (LUTS), often secondary to benign prostatic hyperplasia, are a common problem for older men. Lifestyle factors, including physical activity and sedentariness, may be important LUTS risk factors and suitable targets for intervention. OBJECTIVE: To determine whether physical activity and sedentariness are associated with LUTS incidence and progression. DESIGN: The Health Professionals Follow-up Study is a prospective cohort of men that began in 1986. Follow-up for LUTS is complete through 2008. PARTICIPANTS: Men aged 40-75 years at enrollment and members of health professions. MAIN MEASURES: Total weekly metabolic equivalent of task (MET)-hour scores were calculated and were categorized (< 9, 9 to < 21, 21 to < 42, 42 to < 63, ≥ 63 MET-hours/week). Participants reported their average time/week spent sitting watching television as a measure of sedentariness, which was categorized (< 1, 1-3, 4-10, 11-29, ≥ 30 h/week). Participants completed the International Prostate Symptom Score survey and reported treatments for LUTS periodically. Cox proportional hazards regression was used to estimate multivariable-adjusted hazard ratios (HR) of physical activity and television watching with LUTS incidence and progression. KEY RESULTS: After multivariable adjustment, including for body mass index (BMI), men with the highest physical activity were 19% (HR = 0.81, 95% CI = 0.74-0.89; p trend < 0.0001) less likely to develop incident moderate or worse LUTS than men in the lowest category. Men who watched television ≥ 30 h/week were 24% (HR = 1.24, 95% CI = 1.05-1.45; p trend = 0.004) more likely to develop incident moderate or worse LUTS than men who watched < 1 h/week. These associations persisted after mutual adjustment. We observed no associations with LUTS progression. CONCLUSIONS: In this large prospective study, more activity and less sedentariness were associated with lower risk of incident LUTS independent of one another and BMI. Physical inactivity and sedentariness were not associated with LUTS worsening. Increasing physical activity and reducing sedentariness may be strategies for preventing LUTS in addition to their well-established benefits for other diseases.

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