Clinical Significance of Serum Adipokines according to Body Mass Index in Patients with Clinically Localized Prostate Cancer Undergoing Radical Prostatectomy Leptin increases prostate cancer aggressiveness Relationship between serum adiponectin and prostate cancer grade. Prostate cancer and adiponectin. A study of caloric restriction versus standard diet in overweight men with newly diagnosed prostate cancer: a randomized controlled trial. A 25-year prospective study of plasma adiponectin and leptin concentrations and prostate cancer risk and survival. Prostate cancer risk and serum levels of insulin and leptin: a population-based study. The influence of overweight and insulin resistance on breast cancer risk and tumour stage at diagnosis: a prospective study Serum leptin: a marker of prostate cancer irrespective of obesity. Correlation of body mass index and leptin with tumor size and stage of disease in hormone-dependent postmenopausal breast cancer: preliminary results and therapeutic implications Insulin resistance is inversely related to prostate cancer: a prospective study in Northern Sweden. Adipocytokines, Inflammation, and Breast Cancer Risk in Postmenopausal Women: A Prospective Study Obesity and mortality in men with locally advanced prostate cancer Circulating Adipokines and Inflammatory Markers and Postmenopausal Breast Cancer Risk. Association of C-peptide and leptin with prostate cancer incidence in the Health Professionals Follow-up Study Insulin, insulin-like growth factor-I, and risk of breast cancer in postmenopausal women. Stronger Association between Obesity and Biochemical Progression after Radical Prostatectomy among Men Treated in the Last 10 Years
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 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 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 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 INTRODUCTION Obese men have an increased risk of prostate cancer (PCa)-specific mortality . Potential mechanisms include insulin and related proteins . We investigate whether a short-term caloric restriction diet in overweight/obese men with newly diagnosed PCa can lead to measurable changes in patient anthropometrics and insulin-related proteins . METHODS Overweight and obese PCa patients choosing active surveillance or radical prostatectomy were r and omized to a 6-week , caloric-restricted diet or to continue their current diet . Changes from baseline to end of study in anthropometrics , dietary constituents and serum proteins ( insulin , c-peptide , IGF-1 , adiponectin , IGF-BP3 ) were compared between the intervention and control groups using a Generalized Estimating Equation model . RESULTS Nineteen patients were r and omized to the intervention ( N = 10 ) or control ( N = 9 ) group . Men in the intervention group had a 1.7 % ( 3.7 lbs ) mean decline in weight versus 1.0 % ( 2.0 lbs ) in controls ( P < 0.05 ) , and a reduced intake of calories , total and saturated fat , protein and starch ( all P < 0.1 compared to controls ) . There was a significant difference ( P = 0.002 ) in mean serum IGFBP-3 between the intervention ( + 2.8 % ) and control group ( -6.9 % ) . Other biomarkers changed with the diet intervention to a degree similar to previous weight loss studies but were not statistically significant compared with controls . CONCLUSION In this small pilot study , a 6-week caloric restricted diet in men with newly diagnosed PCa produced changes in weight , diet and serum proteins possibly related to prognosis . These results support larger-scale trials testing longer-term weight loss effects on potential PCa progression biomarkers 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 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 It is hypothesized that insulin resistance and related metabolic factors may influence breast cancer risk , however the epidemiological evidence remains inconclusive . We conducted a case – control study nested in a prospect i ve cohort in Northern Sweden , to clarify the associations of  body mass index ( BMI ) , leptin , adiponectin , C-peptide , and glycated haemoglobin ( HbA1c )  with breast cancer risk . We also investigated whether these associations may be modified by age at diagnosis , tumour stage , and oestrogen and progesterone receptor status . During follow-up , 561 women developed invasive breast cancer and 561 matched controls were selected .  Conditional logistic regression was used to calculate odds ratios ( OR ) as estimates of relative risk , and 95 % confidence intervals ( CI ) . The associations of BMI , leptin and HbA1c with breast cancer risk differed significantly according to whether the tumour was diagnosed as stage I or stage II – IV ( Pheterogeneity all < 0.05 ) . These factors were significantly inversely associated with risk in the group of stage I tumours , with ORs for top vs. bottom tertile for BMI of 0.48 ( 95 % CI , 0.30–0.78 , Ptrend = 0.004 ) ; leptin , 0.64 ( 95 % CI , 0.41–1.00 , Ptrend = 0.06 ) ; and HbA1c , 0.47 ( 95 % CI , 0.28–0.80 , Ptrend = 0.005 ) . For stage II – IV tumours , there was a suggestion of an increased risk with higher levels of these factors . There were no significant differences in the associations of BMI , leptin , adiponectin , C-peptide and HbA1c with breast cancer risk in subgroups of age at diagnosis or tumour receptor status . This prospect i ve study suggests that BMI , leptin and HbA1c influence breast tumour initiation and progression 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 Obesity is considered the most important risk and prognostic factor for estrogen-dependent breast cancer in postmenopausal women . Adipokines , in particular leptin , are at the center of the etiopathogenetic mechanisms by which obesity and related metabolic disorders influence breast cancer risk and its prognosis . The present prospect i ve observational study aims to investigate the relationship between  body mass index ( BMI ) , serum levels of leptin and proinflammatory cytokines , and breast cancer prognostic factors . In the study , 98 postmenopausal and 82 premenopausal patients with ER-positive breast cancer participated . During the same study period , 221 control subjects were simultaneously recruited . Women underwent baseline measurements pre-operatively , before any surgical and systemic treatments . Pathologic characteristics of tumors were abstract ed from pathology reports . Leptin and proinflammatory cytokines were assayed in stored fasting blood specimens . In postmenopausal breast cancer patients , BMI , leptin , and interleukin-6 significantly correlated with pathological tumor classification ( pT ) and TNM stage . Multivariate regression analysis showed that BMI and leptin , but not interleukin-6 , were independent predictive variables of pT and TNM stage . Our results seem to suggest a twofold role of leptin in the etiopathogenesis of postmenopausal estrogen-positive breast cancer . Indeed , leptin reflects the total amount of fat mass , which correlates to aromatase activity and subsequent estrogens levels . Further studies are warranted to clarify the role of leptin and interleukin-6 in breast carcinogenesis and identify new therapeutic options , beyond the use of aromatase inhibitors , acting selectively on adipokine-driven pathways 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 Obesity is a known risk factor for postmenopausal breast cancer ; it has been postulated that adipocytokines may mediate this association . We explored the relationship between three markers altered by obesity : leptin , adiponectin , and soluble tumor necrosis factor receptor 2 ( sTNF-R2 ) , an inflammatory marker , with breast cancer risk in postmenopausal women . A nested case – control study of postmenopausal women was conducted within CLUE II , a prospect i ve population -based cohort .  Baseline plasma levels of leptin , adiponectin , and sTNF-R2  were assayed in 272 female breast cancer cases and 272 controls matched on age , date , and hour of blood draw .  Conditional logistic regression was used to estimate matched odds ratios ( OR ) and 95 % confidence intervals ( CI ) . sTNF-R2 and leptin were independently positively associated with breast cancer risk in adjusted models . The OR for breast cancer comparing the highest to lowest tertile was 2.44 ( 95 % CI : 1.30–4.58 ) for sTNF-R2 and 1.98 ( 95 % CI : 1.20–3.29 ) for leptin . While higher levels of adiponectin were protective ( OR for the lowest tertile = 1.63 ; 95 % CI : 1.02–2.60 ) , there was no dose response . A 20 % reduction in the breast cancer risk associated with overweight/obesity was observed when sTNF-R2 alone was included in multivariable models . Including both sTNF-R2 and adiponectin in the models result ed in a 29 % reduction in the OR . Adipocytokines and sTNF-R2 are important factors in the etiology of postmenopausal breast cancer due to adiposity . This study informs our underst and ing of the relationship between obesity , inflammation , and postmenopausal breast cancer and identifies potential biomarkers . Cancer Epidemiol Biomarkers Prev ; 22(7 ) ; 1319–24 . © 2013 AACR Greater body mass index ( BMI ) is associated with shorter time to prostate‐specific antigen ( PSA ) failure following radical prostatectomy and radiation therapy ( RT ) . Whether BMI is associated with prostate cancer‐specific mortality ( PCSM ) was investigated in a large r and omized trial of men treated with RT and and rogen deprivation therapy ( ADT ) for locally advanced prostate cancer BACKGROUND Adipokines and inflammation may provide a mechanistic link between obesity and postmenopausal breast cancer , yet epidemiologic data on their associations with breast cancer risk are limited . METHODS In a case-cohort analysis nested within the Women 's Health Initiative Observational Study , a prospect i ve cohort of postmenopausal women , baseline plasma sample s from 875 incident breast cancer case patients and 839 subcohort participants were tested for levels of seven adipokines , namely leptin , adiponectin , resistin , interleukin-6 , tumor necrosis factor-α , hepatocyte growth factor , and plasminogen activator inhibitor-1 , and for C-reactive protein ( CRP ) , an inflammatory marker . Data were analyzed by multivariable Cox modeling that included established breast cancer risk factors and previously measured estradiol and insulin levels . All statistical tests were two-sided . RESULTS The association between plasma CRP levels and breast cancer risk was dependent on hormone therapy ( HT ) use at baseline ( P interaction = .003 ) . In a model that controlled for multiple breast cancer risk factors including body mass index ( BMI ) , estradiol , and insulin , CRP level was positively associated with breast cancer risk among HT nonusers ( hazard ratio for high vs low CRP levels = 1.67 , 95 % confidence interval = 1.04 to 2.68 , P trend = .029 ) . None of the other adipokines were statistically significantly associated with breast cancer risk . Following inclusion of CRP , insulin , and estradiol in a multivariable model , the association of BMI with breast cancer was attenuated by 115 % . CONCLUSION These data indicate that CRP is a risk factor for postmenopausal breast cancer among HT nonusers . Inflammatory mediators , together with insulin and estrogen , may play a role in the obesity-breast cancer relation 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 BACKGROUND The positive association between obesity and postmenopausal breast cancer has been attributed , in part , to the fact that estrogen , a risk factor for breast cancer , is synthesized in adipose tissue . Obesity is also associated with high levels of insulin , a known mitogen . However , no prospect i ve studies have directly assessed associations between circulating levels of insulin and /or insulin-like growth factor (IGF)-I , a related hormone , and the risk of breast cancer independent of estrogen level . METHODS We conducted a case-cohort study of incident breast cancer among nondiabetic women who were enrolled in the Women 's Health Initiative Observational Study ( WHI-OS ) , a prospect i ve cohort of 93,676 postmenopausal women .  Fasting serum sample s obtained at study entry from 835 incident breast cancer case subjects and from a subcohort of 816 r and omly chosen WHI-OS subjects were tested for levels of insulin , glucose , total IGF-I , free IGF-I , insulin-like growth factor binding protein-3 , and estradiol .  Multivariable Cox proportional hazards models were used to estimate associations between levels of the serologic factors and baseline characteristics ( including body mass index [ BMI ] ) and the risk of breast cancer . All statistical tests were two-sided . Results Insulin levels were positively associated with the risk of breast cancer ( hazard ratio [ HR ] for highest vs lowest quartile of insulin level = 1.46 , 95 % confidence interval [ CI ] = 1.00 to 2.13 , P(trend ) = .02 ) ; however , the association with insulin level varied by hormone therapy ( HT ) use ( P(interaction ) = .01 ) . In a model that controlled for multiple breast cancer risk factors including estradiol , insulin level was associated with breast cancer only among nonusers of HT ( HR for highest vs lowest quartile of insulin level = 2.40 , 95 % CI = 1.30 to 4.41 , P(trend ) < .001 ) . Obesity ( BMI > or=30 kg/m(2 ) ) was also associated with the risk of breast cancer among nonusers of HT ( HR for BMI > or=30 kg/m(2 ) vs 18.5 to < 25 kg/m(2 ) = 2.12 , 95 % CI = 1.26 to 3.58 , P(trend ) = .003 ) ; however , this association was attenuated by adjustment for insulin ( P(trend ) = .40 ) . CONCLUSION These data suggest that hyperinsulinemia is an independent risk factor for breast cancer and may have a substantial role in explaining the obesity-breast cancer relationship Background : Prior prospect i ve cohort studies found that obesity was associated with increased risk of prostate cancer death . However , in the last 20 years dramatic changes in both the extent of obesity and prostate cancer screening and treatment have occurred . Whether the association between obesity and aggressive disease has changed as a result of these temporal changes is unclear . Methods : The study population consisted of 2,832 men treated by anatomic radical retropubic prostatectomy between 1985 and 2004 by a single surgeon . We evaluated the associations of obesity ( body mass index ≥30 kg/m2)with tumor stage and grade using logistic regression and with biochemical progression using Cox proportional hazards regression . We examined whether these associations have changed over the last 20 years . Results : On multivariable analysis , the strength of the positive association between obesity and high- grade disease increased over time whereas the strength of the positive association between obesity and positive surgical margins decreased over time . The strength of the positive association between obesity and extraprostatic extension fluctuated over time , although the strongest and only statistically significant association was among men treated since 2000 . The association between obesity and biochemical progression was strongest among men treated since 1995 ( relative risk , 1.90 ; 95 % confidence interval , 1.09 - 3.30 ; P = 0.02 ) . Conclusions : In the current study , with the exception of positive surgical margins , the positive association between obesity and high- grade disease , advanced stage , and biochemical progression after radical retropubic prostatectomy was in general strongest among men treated in the last 10 years . The reasons for these findings are not clear , although factors possibly related to prostate-specific antigen – based screening and /or other temporal changes in prostate cancer diagnosis and treatment may play a role
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 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 .