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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The relationship between obesity and prostate cancer is currently a hotly debated topic, but despite the number of publications devoted to the topic, the actual nature of the relationship remains uncertain. Obesity has been shown to have a direct relationship with the incidence of prostate cancer in a number of studies but an equal number of studies have shown no association. The relationship is further obscured with recent findings that obesity in younger obese men may actually be protective against prostate cancer. Confounding factors include the lack of correlation of body mass index (BMI) as a measure of central obesity and the lack of consistency in timing of BMI measurements, i.e. before or after diagnosis and in young or advanced adulthood. Evidence for increased BMI as a risk factor for prostate cancer is unclear, but less ambiguous is the mounting substantiation that obesity is associated with prognostically worse disease, poorer post-surgical outcomes and increased prostate cancer mortality, irregardless of margin status. From a biologic perspective, one can put forth a number of potential mechanisms by which obesity might promote prostate cancer and/or prostate cancer progression including; low levels of testosterone, increased levels of estrogen, co-existing diabetes or metabolic syndrome, increased circulating insulin-growth factor-one (IGF-1), increased levels of leptin, decreased levels of adiponectin and increased dietary saturated fats. Evidence for the association of these factors with prostate cancer are examined herein. The timing of serum measurements is crucial in elucidating whether these factors have causative influence on prostate cancer or rather are produced by the prostate cancer cells and are better understood as markers of disease. The interaction between obesity and prostate cancer is important to clarify because it will have impact on the prevention, prognostication and treatment of prostate cancer. Future study with careful attention to avoid the methodological pitfalls of the past need be accomplished to bear out the nature of the interaction of obesity and prostate cancer.
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PMID:Obesity and prostate cancer. 1667 23

Obesity is a risk factor for prostate cancer, and plasma levels of the adipokine, adiponectin, are low in the former but high in the latter. Adiponectin has been shown to modulate cell proliferation and apoptosis, suggesting that adiponectin and its receptors (Adipo-R1, Adipo-R2) may provide a molecular association between obesity and prostate carcinogenesis. We show for the first time, the protein distribution of Adipo-R1 and Adipo-R2 in LNCaP and PC3 cells, and in human prostate tissue. Using real-time RT-PCR we provide novel data demonstrating the differential regulation of Adipo-R1 and Adipo-R2 mRNA expression by testosterone, 5-alpha dihydrotestosterone, beta-estradiol, tumour necrosis factor-alpha, leptin, and adiponectin in LNCaP and PC3 cells. Our findings suggest that adiponectin and its receptors may contribute to the molecular association between obesity and prostate cancer through a complex interaction with other hormones and cytokines that also play important roles in the pathophysiology of obesity and prostate cancer.
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PMID:The regulation of adiponectin receptors in human prostate cancer cell lines. 1689 22

Affecting over 30% of the population, obesity is an epidemic in the United States and is associated with multiple chronic medical problems. Obesity is also associated with numerous hormonal changes, many of which have been implicated in prostate cancer development and progression. Although, on the whole, controversy exists over whether obesity increases the risk of prostate cancer, data strongly suggest that obesity is a significant risk factor for prostate cancer death. In this review, we discuss the epidemiologic data surrounding obesity and prostate cancer. We also discuss some of the sequelae of obesity and their relationships with prostate cancer, including alterations in insulin, the insulin-like growth factor axis, and leptin levels; insulin resistance; and diabetes. Although a complete overview of all the various dietary and lifestyle factors that are associated with obesity and prostate cancer risk is beyond the scope of this review, we discuss data concerning the relationship between a high-fat diet and prostate cancer.
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PMID:Examining the relationship between obesity and prostate cancer. 1698 80

Calorie restriction can inhibit or delay carcinogenesis, reportedly due to a reduction in calorie intake rather than by concurrent changes in body mass and/or composition. Our objective was to test the hypothesis that body mass and/or composition have an important effect, independent of energy intake, on the benefits or hazards associated with calorie restriction or overeating, respectively. In the first experiment, transgenic mice that spontaneously develop prostate cancer [transgenic adenocarcinoma of mouse prostate (TRAMP)] were housed at 27 degrees C or 22 degrees C and pair fed the same diet for 21 weeks (95% of ad libitum intake at 27 degrees C). In the second experiment, TRAMP mice were housed at 27 degrees C or 22 degrees C and fed the same diet ad libitum for 21 weeks. Despite a similar calorie intake, pair-fed mice at 27 degrees C (PF27) were heavier (28.3 +/- 3.3 versus 17.6 +/- 1.6 g at 21 weeks; P < 0.001; mean +/- SD) and had greater fat (6.4 +/- 2.1 versus 1.9 +/- 0.3 g; P < 0.001) and lean mass (P < 0.001) than pair-fed mice at 22 degrees C. Furthermore, PF27 mice had greater levels of serum leptin (P < 0.001), lower levels of adiponectin (P < 0.05), and a greater frequency of prostatic adenocarcinoma (P < 0.05). In contrast, ad libitum-fed mice housed at 22 degrees C consumed approximately 30% more calories than ad libitum-fed mice at 27 degrees C, but there was no difference between groups in body composition or cancer progression. These results imply that the ability of calorie restriction to inhibit or delay cancer incidence and progression is mediated in part by changes in energy balance, body mass, and/or body composition rather than calorie intake per se, suggesting that excess calorie retention, rather than consumption, confers cancer risk.
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PMID:Cancer progression in the transgenic adenocarcinoma of mouse prostate mouse is related to energy balance, body mass, and body composition, but not food intake. 1718 79

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 prospective 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 androgens, 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.
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PMID:Insulin resistance is inversely related to prostate cancer: a prospective study in Northern Sweden. 1727 97

Genistein is a plant-derived compound possessing well-known preventive activity in breast and prostate cancer, cardiovascular diseases and post-menopausal problems. Lately, the interests in genistein have widened. The studies concerning effects of genistein performed on animals and humans revealed other aspects of its action -- the metabolic alterations at the cellular level and in the whole organism. It was shown that genistein decreased body and fat tissue weight gains accompanied by reduced food intake. After ingestion of dietary genistein, the alterations in concentrations of hormones such as: insulin, leptin, thyroid hormones, adrenocorticotropic hormone, cortisol and corticosterone were observed. The changes in lipid parameters -- triglycerides and cholesterol were also noticed as a consequence of genistein administration. Moreover, the altered expression of genes engaged in lipid metabolism, disturbed glucose transport into cells, affected lipolysis and lipogenesis and changed ATP synthesis were found as a result of genistein action.
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PMID:Genistein--a dietary compound inducing hormonal and metabolic changes. 1758 43

Circulating insulin-like growth factor binding protein 1 (IGFBP-1), leptin, and insulin are 3 proteins modified by obesity and have been associated with cancer at several sites in past studies. We conducted a cross-sectional study to describe the correlation of these proteins with gender, race/ethnicity, anthropometric indexes, and dietary and lifestyle factors. We measured fasting plasma levels of IGFBP-1, leptin, and C-peptide, used here as a stable measure of insulin secretion, in a random sample of 450 male and 352 postmenopausal female Hawaii and Los Angeles Multiethnic Cohort Study (MEC) participants (age range 47-82 yr at blood draw). Through a series of multiple linear regressions, we found that the most parsimonious model for plasma IGFBP-1 included inverse associations with age, body mass index (BMI), and regular soda intake. A term for interaction between age and BMI was positively associated with plasma IGFBP-1. Adjusted mean plasma leptins were highest among Whites and African Americans and lowest among Hawaiians and Japanese Leptin was also inversely associated with age and positively associated with the interaction between age and race/ethnicity, female gender, and BMI. A model with only race/ethnicity and BMI (positive association) was best for plasma C-peptide. Adjusted means for C-peptide were highest for Japanese and Whites and lowest for African Americans. The overall percent of variance in protein levels explained by these models was low for IGFBP-1(R2=0.17) and C-peptide (R(3)=0.11) and higher for leptin (R(2)=0.57). We saw no clear correlation between racial/ethnic trends in protein levels with those of colorectal, breast, or prostate cancer incidence rates in the MEC. Research to clarify factors associated with determination of these proteins and their relationship with cancer etiology is warranted.
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PMID:Lifestyle and dietary correlates of plasma insulin-like growth factor binding protein-1 (IGFBP-1), leptin, and C-peptide: the Multiethnic Cohort. 1764 Jan 59

Prior studies report slightly lower prostate-specific antigen (PSA) levels among obese men. To understand this effect, we investigated the association between PSA and blood HbA1c, C-peptide, leptin and adiponectin levels in African-American (AA) (n=121) and Caucasian (CA) (n=121) men. Among AA men, PSA levels decreased with increasing C-peptide levels (PSA=0.99, 0.93, 0.75 and 0.53 ng ml(-1) across quartiles of C-peptide, respectively; P(trend)=0.005). Among CA men, PSA levels decreased with increasing HbA1c (PSA=0.84, 0.73, 0.77 and 0.45 ng ml(-1) across quartiles of HbA1c, respectively; P(trend)=0.005). This may suggest that metabolic disturbances related to metabolic syndrome or diabetes affect the ability to detect early-stage prostate cancer.
Prostate Cancer Prostatic Dis 2008
PMID:Association between prostate-specific antigen and leptin, adiponectin, HbA1c or C-peptide among African-American and Caucasian men. 1793 44

Although obesity has been consistently linked to an increased risk of several malignancies, including cancers of the colon, gallbladder, kidney, and pancreas, its role in prostate cancer etiology remains elusive. Data on the association between obesity and prostate cancer incidence are inconsistent, and in some studies obesity is associated with an increase in risk of high-grade prostate cancer but with a decrease in risk of low-grade tumors. In contrast, obesity has been consistently associated with an increased risk of prostate cancer aggressiveness and mortality. The differential effects of obesity on subtypes of prostate cancer suggest etiologic heterogeneity in these tumors and complex interactions between androgen metabolism and several putative risk factors, including insulin resistance, diabetes, inflammation, and genetic susceptibility, on prostate cancer risk. Data on the role of abdominal obesity, insulin resistance, and metabolic syndrome in prostate cancer etiology are limited. Obesity has been shown to be associated with a state of low-grade chronic inflammation, and insulin resistance and the metabolic syndrome are associated with adverse metabolic profiles and with higher circulating concentrations of inflammation-related markers, including leptin, interleukin-6, and tumor necrosis factor-, many of which have been shown to enhance tumor growth. Thus, whether obesity and metabolic syndrome modulate the risk of prostate cancer through chronic inflammation needs to be investigated further. Given that the prevalence of obesity and metabolic syndrome is increasing worldwide and that the world population is aging, the roles of obesity and metabolic syndrome in prostate carcinogenesis warrant further clarification.
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PMID:Obesity, metabolic syndrome, and prostate cancer. 1826 78

Obesity has been linked with an increased risk of prostate cancer. The formation of toxic free oxygen radicals has been implicated in obesity mediated disease processes. Leptin is one of the major cytokines produced by adipocytes and controls body weight homeostasis through food intake and energy expenditure. The rationale of the study was to determine the impact of leptin on the metastatic potential of androgen-sensitive (LNCaP) cells as well as androgen-insensitive (PC-3 and DU-145) cells. At a concentration of 200 nm, LNCaP cells showed a significant increase (20% above control; P < .0001) in cellular proliferation without any effect on androgen-insensitive cells. Furthermore, exposure to leptin caused a significant (P < .01 to P < .0001) dose-dependent decrease in migration and invasion of PC3 and Du-145 prostate carcinoma cell lines. At the molecular level, exposure of androgen-independent prostate cancer cells to leptin stimulates the phosphorylation of MAPK at early time point as well as the transcription factor STAT3, suggesting the activation of the intracellular signaling cascade upon leptin binding to its cognate receptor. Taken together, these results suggest that leptin mediates the invasive potential of prostate carcinoma cells, and that this effect is dependent on their androgen sensitivity.
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PMID:Differential effects of leptin on the invasive potential of androgen-dependent and -independent prostate carcinoma cells. 1858 49


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