title: Serum leptin: a marker of prostate cancer irrespective of obesity. Leptin increases prostate cancer aggressiveness Association of C-peptide and leptin with prostate cancer incidence in the Health Professionals Follow-up Study Prostate cancer and adiponectin. The Diagnostic Value of Adiponectin Multimers in Healthy Men Undergoing Screening for Prostate Cancer In1-ghrelin, a splice variant of ghrelin gene, is associated with the evolution and aggressiveness of human neuroendocrine tumors: Evidence from clinical, cellular and molecular parameters Prostate cancer risk and serum levels of insulin and leptin: a population-based study. Insulin resistance is inversely related to prostate cancer: a prospective study in Northern Sweden. Association between prediagnostic biomarkers of inflammation and endothelial function and cancer risk: a nested case-control study. Circulating ghrelin levels are decreased in human obesity. Clinical Significance of Serum Adipokines according to Body Mass Index in Patients with Clinically Localized Prostate Cancer Undergoing Radical Prostatectomy Relationship between serum adiponectin and prostate cancer grade. A 25-year prospective study of plasma adiponectin and leptin concentrations and prostate cancer risk and survival.
abstract: INTRODUCTION High expression of leptin receptors have been observed in the prostate cancer in various clinical studies ; however the association of serum leptin with carcinoma prostate remains unresolved . We studied association , between serum leptin and carcinoma prostate in Asian ( Indian ) population and its association with obesity . MATERIAL AND METHODS 30 prospect i ve cases of cancer prostate and 30 age matched controls were included in this study . Body mass index ( BMI ) was estimated and categorized in 4 groups by WHO criteria . Waist hip ratio ( WHR ) was calculated and divided into three groups .  Serum leptin  was estimated by s and wich ELISA technique ( DRG leptin ELISA kit , Marburg , Germany ) . RESULTS Both the groups were comparable for age , WHR and BMI . Serum leptin was significantly higher in patients with cancer prostate as compared to controls ( median 14.18 ng/ml vs. 1.63 ng/ml ; p < 0.001 ) . The level of leptin was found to have positive correlation with BMI and WHR in controls ( r=0.485 , p=0.007 ; r=0.314 , p=0.091 , respectively ) however , no correlation was observed in patients with cancer prostate ( r=0.071 , p=0.711 ; r=0.067 , p=0.725 , respectively ) . There was no correlation between leptin and PSA . The serum leptin level was not related to the Gleason 's score and stage of the carcinoma . CONCLUSIONS This study shows that Prostate cancer is associated with raised serum leptin which is independent of obesity and serum PSA . It hints the role of leptin in pathogenesis of this tumor . It may not be a surrogate marker of aggressiveness . For validation , further studies including a large patient population is required Recent studies indicate that adipose tissue and adipocytokines might affect the development of prostate cancer ( PCa ) . Leptin would have a stimulating effect on prostate cancer cells by inducing promotion and progression , whereas adiponectin would have a protective effect . The aim of this study was to determine the relation between body composition , leptin , and adiponectin levels with the prevalence and aggressiveness of PCa in men of Mendoza , Argentina . Seventy volunteers between 50 and 80 years ( 35 healthy men as control group and 35 with PCa ) were selected . The PCa group was subclassified according to the Gleason Score ( GS ) . Digital rectal examination , transrectal ultrasound , and prostatic biopsy were performed ; PSA , testosterone , leptin , and adiponectin levels  were determined ; and a nutritional interview including anthropometric measurements and a food frequency question naire was carried out . Statistical analysis was performed by Student t test , ANOVA I , and Bonferroni ( p < 0.05 ) . Body mass index and percentage of body fat mass were not statistically different between PCa and control groups . However , body fat mass was higher in subjects with more aggressive tumors ( p = 0.032 ) . No differences were observed regarding leptin levels between the groups . Nevertheless , leptin levels were higher in subjects with high GS ( p < 0.001 ) . Adiponectin levels showed no statistical differences regarding the presence and aggressiveness of the tumor ( p = 0.131 ) . Finally , consumption and nutrient intake did not differ in the studied groups . In conclusion , body composition and leptin are related to the PCa aggressiveness but not with its prevalence Abstract Purpose Hyperinsulinemia is hypothesized to influence prostate cancer risk . Thus , we evaluated the association of circulating C-peptide , which is a marker of insulin secretion , and leptin , which is secreted in response to insulin and influences insulin sensitivity , with prostate cancer risk . Methods We identified prostate cancer cases ( n = 1,314 ) diagnosed a mean of 5.4 years after blood draw and matched controls ( n = 1,314 ) in the Health Professionals Follow-up Study .  Plasma C-peptide and leptin concentrations were measured by ELISA .  Odds ratios ( ORs ) and 95 % confidence intervals ( CI ) were estimated taking into account the matching factors age and history of a PSA test before blood draw and further adjusting for body mass index , diabetes , and other factors . Results Neither C-peptide ( quartile [Q]4 vs. Q1 : OR 1.05 , 95 % CI 0.82–1.34 , p-trend = 0.95 ) nor leptin ( Q4 vs. Q1 : OR 0.85 , 95 % CI 0.65–1.12 , p-trend = 0.14 ) was associated with prostate cancer risk . Further , neither was associated with risk of advanced or lethal disease ( n = 156 cases ; C-peptide : Q4 vs. Q1 , OR 1.18 , 95 % CI 0.69–2.03 , p-trend = 0.78 ; leptin : Q4 vs. Q1 , OR 0.74 , 95 % CI 0.41–1.36 , p-trend = 0.34 ) . Conclusions In this large prospect i ve study , circulating C-peptide and leptin concentrations were not clearly associated with risk of prostate cancer overall or aggressive disease . Well into the PSA era , our findings do not appear to be supportive of the hypothesis that hyperinsulinemia influences risk of total or aggressive prostate cancer OBJECTIVES To search for any relation between plasma adiponectin levels and the cellular differentiation or progression of prostate cancer ( PCa ) . PCa is becoming an increasingly important public health problem , particularly for those countries with a trend toward an aging population . Because insulin resistance in the setting of obesity is associated with the development of PCa , we hypothesized that decreased adiponectin levels might underlie the association between PCa and obesity/insulin resistance . METHODS In this study , we investigated plasma adiponectin levels in 30 patients with PCa , 41 subjects with benign prostatic obstruction , and 36 healthy individuals . The body mass index and age of the groups were similar . Patients with PCa were stratified into two groups according to the spread of the disease as organ-confined and advanced disease and into three groups according to grade ( low , intermediate , and high grade determined by a Gleason sum of less than 5 , between 5 and 7 , and more than 7 , respectively ) . RESULTS Plasma adiponectin levels were significantly lower in the PCa group than in the benign prostatic obstruction group or controls ( P < 0.001 for both ) . Additionally , the plasma adiponectin levels were significantly lower in the advanced disease group than in the organ-confined PCa group ( P = 0.012 ) . Significant negative associations were found between plasma adiponectin levels and prostate-specific antigen levels or biopsy Gleason scores in the PCa group . The plasma adiponectin levels of those with high- grade PCa were also significantly lower than those for both the low- grade and intermediate- grade groups ( P < 0.001 for both ) . CONCLUSIONS The results of the present study imply that plasma adiponectin levels are not only lower in patients with PCa but are also negatively associated with the histologic grade and disease stage . Future prospect i ve studies are recommended to establish any causal relation between PCa and plasma adiponectin levels Background : Adiponectin has been reported to have a prohibitory effect on prostate cancer . The goal of this study was to evaluate the diagnostic value of adiponectin multimers for prostate cancer . Methods :  Total adiponectin , high- and low-molecular-weight ( HMW , LMW ) , ratios of these measures , and body mass index ( BMI ) were compared in a prospect i ve prostate cancer – screened cohort .  Multivariable logistic regression was used to assess the association between adiponectin measures , their interaction with BMI , and risk of prostate cancer and Gleason score upgrading from biopsy to prostatectomy . Results : A total of 228 prostate cancer cases and 239 controls were analyzed : 72 ( 31.6 % ) of the cancer cases were high grade ( Gleason grade ≥7 ) . Only percent HMW had a statistically significant relationship with prostate cancer ( P = 0.04 ) . Among normal and overweight men , the risk of prostate cancer increased as percent HMW increased [ OR = 1.24 for a doubling of percent HMW , 95 % confidence interval ( CI ) , 0.41–3.75 and OR = 1.81 ; 95 % CI , 1.02–3.20 , respectively ] , whereas among obese men , the risk of prostate cancer decreased ( OR = 0.62 ; 95 % CI , 0.32–1.18 ) . Among 97 patients who underwent radical prostatectomy , there was no association between Gleason score upgrading and any of the adiponectin multimers . Conclusion : This study was unable to confirm the utility of total adiponectin as a biomarker for prostate cancer risk . For the adiponectin multimers , only HMW showed increases with prostate cancer but not in all weight classes . Impact : Although adiponectin may play a role in the pathogenesis of prostate cancer , our results do not support adiponectin multimers as biomarkers of detection . Cancer Epidemiol Biomarkers Prev ; 23(2 ) ; 309–15 . © 2013 AACR Ghrelin system comprises a complex family of peptides , receptors ( GHSRs ) , and modifying enzymes [ e.g. ghrelin-O-acyl-transferase ( GOAT ) ] that control multiple pathophysiological processes . Aberrant alternative splicing is an emerging cancer hallmark that generates altered proteins with tumorigenic capacity . Indeed , In1-ghrelin and truncated-GHSR1b splicing variants can promote development/progression of certain endocrine-related cancers . Here , we determined the expression levels of key ghrelin system components in neuroendocrine tumor ( NETs ) and explored their potential functional role . Twenty-six patients with NETs were prospect ively/retrospectively studied [ 72 sample s from primary and metastatic tissues ( 30 normal/42 tumors ) ] and clinical data were obtained . The role of In1-ghrelin in aggressiveness was studied in vitro using NET cell lines ( BON-1/QGP-1 ) . In1-ghrelin , GOAT and GHSR1a/1b expression levels were elevated in tumoral compared to normal/adjacent tissues . Moreover , In1-ghrelin , GOAT , and GHSR1b expression levels were positively correlated within tumoral , but not within normal/adjacent sample s , and were higher in patients with progressive vs. with stable/cured disease . Finally , In1-ghrelin increased aggressiveness ( e.g. proliferation/migration ) of NET cells . Altogether , our data strongly suggests a potential implication of ghrelin system in the pathogenesis and /or clinical outcome of NETs , and warrant further studies on their possible value for the future development of molecular biomarkers with diagnostic/prognostic/therapeutic value BACKGROUND In a previous study of Chinese men , we found that men with a higher waist-to-hip ratio ( WHR ) have a higher prostate cancer risk . Because leptin and insulin are related to body fat distribution , we examined whether leptin and insulin were associated with prostate cancer risk . METHODS Blood sample s were collected from 128 case patients with incident prostate cancer and from 306 healthy control subjects r and omly selected from residents of Shanghai , CHINA : Epidemiologic information and anthropometric measurements were collected in personal interviews . Serum leptin , insulin , and sex hormone levels were measured by radioimmunoassay , and  insulin-like growth factor-I ( IGF-I )  was measured by enzyme-linked immunosorbent assay . Multiple logistic regression analyses were used to estimate odds ratios for prostate cancer in relation to serum insulin and leptin levels . All statistical tests were two-sided . RESULTS After adjustment for body mass index , WHR , IGF-I , and sex hormone levels , higher serum insulin levels were associated with a statistically significantly elevated risk of prostate cancer ( P<.001 ) . Men in the highest tertile of insulin levels had a 2.56-fold ( 95 % confidence interval [ CI ] = 1.38 to 4.75 ) risk of prostate cancer compared with men in the lowest tertile . Regardless of the tertile level of WHR , higher serum insulin levels were associated with an increased risk of prostate cancer : Men in the highest tertiles of WHR ( > 0.900 ) and insulin ( > 8.83 microU/mL ) had 8.55 times ( 95 % CI = 2.80 to 26.10 ) the prostate cancer risk of men in the lowest tertiles of both , and those in the lowest tertile of WHR ( < 0.873 ) and highest tertile of insulin had 4.30 times ( 95 % CI = 1.17 to 15.70 ) the risk . By contrast , the association between leptin levels and prostate cancer risk was not statistically significant . CONCLUSION Our results suggest that serum insulin levels may influence the risk of prostate cancer in Chinese men . Further research , especially prospect i ve studies , is needed to confirm these findings in high-risk population s and to clarify the underlying mechanisms involved Factors related to insulin resistance have been implicated in prostate cancer development , however , few analytical studies support such an association . We performed a case control study on 392 prostate cancer cases and 392 matched controls nested in a prospect i ve cohort in Northern Sweden .  Plasma concentrations of C-peptide , leptin , glycated haemoglobin ( HbA1c ) and fasting and post-load glucose were analysed and homeostatic model assessment of insulin resistance ( HOMA-IR ) was calculated . Conditional logistic regression analyses were used to calculate odds ratios ( OR ) of prostate cancer . High levels of C-peptide , HOMA-IR , leptin and HbA1c were associated with significant decreases in risk of prostate cancer , with ORs for top vs. bottom quartile for C-peptide of 0.59 ( 95 % Confidence Interval [ CI ] , 0.40 - 0.89 ; p(trend ) = 0.008 ) , HOMA-IR 0.60 ( 95 % CI , 0.38 - 0.94 ; p(trend ) = 0.03 ) , leptin 0.55 ( 95 % CI , 0.36 - 0.84 ; p(trend ) = 0.006 ) and HbA1c 0.56 ( 95 % CI , 0.35 - 0.91 ; p(trend ) = 0.02 ) . All studied factors were strongly inversely related to risk among men less than 59 years of age at blood sampling , but not among older men , with a significant heterogeneity between the groups for leptin ( p(heterogeneity ) = 0.006 ) and fasting glucose ( p(heterogeneity ) = 0.03 ) . C-peptide and HOMA-IR were strongly inversely related to non-aggressive cancer but were non-significantly positively related to risk of aggressive disease ( p(heterogeneity ) = 0.007 and 0.01 , respectively ) . Our data suggest that and rogens , which are inversely associated with insulin resistance , are important in the early prostate cancer development , whereas insulin resistance related factors may be important for tumour progression Experimental and prevalent case-control studies suggest an association between biomarkers of inflammation , endothelial function , and adiposity and cancer risk , but results from prospect i ve studies have been limited . The authors ' objective was to prospect ively examine the relations between these biomarkers and cancer risk . A nested case-control study was design ed within the Supplémentation en Vitamines et Minéraux Antioxydants ( SU.VI.MAX ) Study , a nationwide French cohort study , to include all first primary incident cancers diagnosed between 1994 and 2007 ( n = 512 ) . Cases were matched with r and omly selected controls ( n = 1,024 ) on sex , age ( in 2-year strata ) , body mass index ( weight (kg)/height (m)(2 ) ; < 25 vs. ≥25 ) , and SU.VI.MAX intervention group . Conditional logistic regression was used to study the associations between prediagnostic levels of high-sensitivity C-reactive protein ( hs-CRP ) , adiponectin , leptin , soluble intercellular adhesion molecule 1 ( sICAM-1 ) , soluble vascular cell adhesion molecule 1 , soluble E-selectin , and monocyte chemoattractant protein 1 and cancer risk . All statistical tests were 2-sided . Plasma sICAM-1 level was positively associated with breast cancer risk ( for quartile 4 vs. quartile 1 , multivariate odds ratio ( OR ) = 1.86 , 95 % confidence interval ( CI ) : 1.06 , 3.26 ; P(trend ) = 0.048 ) . Plasma hs-CRP level was positively associated with prostate cancer risk ( for quartile 4 vs. quartile 1 , multivariate OR = 3.04 , 95 % CI : 1.28 , 7.23 ; P(trend ) = 0.03 ) . These results suggest that prediagnostic hs-CRP and sICAM-1 levels are associated with increased prostate and breast cancer risk , respectively Ghrelin is a novel endogenous natural lig and for the growth hormone ( GH ) secretagogue receptor that has recently been isolated from the rat stomach . Ghrelin administration stimulates GH secretion but also causes weight gain by increasing food intake and reducing fat utilization in rodents . To investigate the possible involvement of ghrelin in the pathogenesis of human obesity , we measured body composition ( by dual X-ray absorption ) as well as fasting plasma ghrelin concentrations ( radioimmunoassay ) in 15 Caucasians ( 8 men and 7 women , 31+/-9 years of age , 92+/-24 kg body wt , and 29+/-10 % body fat , mean + /- SD ) and 15 Pima Indians ( 8 men and 7 women , 33+/-5 years of age , 97+/-29 kg body wt , and 30+/-8 % body fat ) .  Fasting plasma ghrelin was negatively correlated with percent body fat ( r = -0.45 ; P = 0.01 ) , fasting insulin ( r = -0.45 ; P = 0.01 ) and leptin ( r = -0.38 ; P = 0.03 ) concentrations . Plasma ghrelin concentration was decreased in obese Caucasians as compared with lean Caucasians ( P < 0.01 ) . Also , fasting plasma ghrelin was lower in Pima Indians , a population with a very high prevalence of obesity , compared with Caucasians ( 87+/-28 vs. 129+/-34 fmol/ml ; P < 0.01 ) . This result did not change after adjustment for fasting plasma insulin concentration . There was no correlation between fasting plasma ghrelin and height . Prospect i ve clinical studies are now needed to establish the role of ghrelin in the pathogenesis of human obesity Purpose The aim of this study was to investigate the clinical significance of 7 circulating adipokines according to body mass index ( BMI ) in Korean men with localized prostate cancer ( PCa ) undergoing radical prostatectomy ( RP ) .  Material s and Methods Sixty-two of 65 prospect ively enrolled patients with clinical ly localized PCa who underwent RP between 2015 and 2016 were evaluated . Patients were classified into 2 groups according to their BMI : non-obese ( < 25 kg/m2 ) and obese ( ≥25 kg/m2 ) . The adipokines evaluated were interleukin-2 , insulin-like growth factor 1 ( IGF-1 ) , chemerin , C-X-C motif chemokine 10 , adiponectin , leptin , and resistin . Multivariate logistic regression analysis was used to identify the independent predictors of advanced tumor stage . Results We found that obese patients with PCa who underwent RP had a higher incidence of tumors with a high Gleason score ( ≥8 ) , pathological T3 ( pT3 ) stage , and positive extraprostatic extension than patients with a normal BMI . Additionally , patients with obesity showed significantly lower serum adiponectin and higher serum leptin levels , but did not show differences in other adipokines . Multivariate analysis demonstrated that IGF-1 ( odds ratio [OR]=1.03 ) was identified as a predictor of advanced tumor stage ( ≥pT3 ) in the overall population . However , only leptin remained an independent predictive factor for advanced tumor stage ( ≥pT3 ) ( OR=1.15 ) in patients with obesity . Conclusions In conclusion , our results indicate that a higher leptin level in obese men can be considered a risk factor for aggressive PCa . This prospect i ve study provides greater insight into the role of circulating adipokines in Korean patients with PCa undergoing RP , particularly in patients with obesity BACKGROUND Obesity is associated with prostate cancer ( PCA ) grade , but the mechanism behind this relationship is not understood . Adiponectin is an adipokine that has been linked with the development of hormonally sensitive carcinomas , including prostate cancer . We evaluated the relationship between serum  adiponectin and Gleason score ( GS ) in a prospect i ve series of patients seen in a single institution . METHODS Localized PCA patients evaluated at Dana-Farber Cancer Institute between 2001 and 2005 who enrolled in a prospect i ve serum banking protocol were eligible for this study . Patients with prior hormonal therapy and /or metastatic disease were excluded . High- grade disease was defined as biopsy or radical prostatectomy ( RP ) GS of 7 or higher . Logistic regression models were used to assess the relationship between high- grade disease and adiponectin levels while adjusting for other potential prognostic variables . RESULTS There were 539 patients included in this study , of whom 199 had undergone RP . Median age was 60 years . Median PSA was 5.1 ng/dl .  Biopsy GS of 7 or higher was seen in 46.9 % of patients . For biopsy GS , higher PSA , older age , and higher BMI were significantly associated with increased odds of GS 7 or higher , but adiponectin was not . In men undergoing RP , there was a significant inverse relationship between pathologic GS and adiponectin dichotomized at the median , due to a significantly higher rate of upgrading in patients with lower adiponectin ( P = 0.014 ) . CONCLUSIONS Although there was no association between biopsy GS and adiponectin , in patients who had undergone RP , lower adiponectin was independently associated with high- grade prostate cancer BACKGROUND Adipocytokines may mediate the association between adiposity and lethal prostate cancer outcomes . METHODS In the Physicians ' Health Study , we prospect ively examined the association of prediagnostic plasma concentrations of adiponectin and leptin with risk of developing incident prostate cancer ( 654 cases diagnosed 1982 - 2000 and 644 age-matched controls ) and , among cases , risk of dying from prostate cancer by 2007 . RESULTS Adiponectin concentrations were not associated with risk of overall prostate cancer . However , men with higher adiponectin concentrations had lower risk of developing high- grade or lethal cancer ( metastatic or fatal disease ) . The relative risk ( 95 % CI ) comparing the highest quintile to the lowest ( Q5 vs Q1 ) was 0.25 ( 95 % CI 0.07 - 0.87 ; P(trend ) = 0.02 ) for lethal cancer . Among all the cases , higher adiponectin concentrations predicted lower prostate cancer-specific mortality [ hazard ratio (HR)(Q5 vs Q1)= 0.39 ; 95 % CI 0.17 - 0.85 ; P(trend ) = 0.02 ] , independent of body mass index ( BMI ) , plasma C-peptide ( a marker of insulin secretion ) , leptin , clinical stage , and tumor grade . This inverse association was apparent mainly among men with a BMI > or=25 kg/m(2 ) ( HR(Q5 vs Q1)= 0.10 ; 95 % CI 0.01 - 0.78 ; P(trend ) = 0.02 ) , but not among men of normal weight ( P(trend ) = 0.51 ) . Although the correlation of leptin concentrations with BMI ( r = 0.58 , P < 0.001 ) was stronger than that of adiponectin ( r = -0.17 , P < 0.001 ) , leptin was unrelated to prostate cancer risk or mortality . CONCLUSIONS Higher prediagnostic adiponectin ( but not leptin ) concentrations predispose men to a lower risk of developing high- grade prostate cancer and a lower risk of subsequently dying from the cancer , suggesting a mechanistic link between obesity and poor prostate cancer outcome
target: Conclusions The current evidence does not suggest an association between leptin and PCa outcome .
  However , there may be an inverse association between adiponectin and the incidence of advanced PCa that should be investigated by further studies .
background: Background Obesity has been proposed as a risk factor for prostate cancer ( PCa ) .
  In obesity , serum levels of the appetite-regulating hormones — leptin , adiponectin , and ghrelin — become deregulated .
  Objective To explore whether serum levels of appetite-regulating hormones associate with the incidence of PCa , the incidence of advanced disease , or PCa-specific mortality .