Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin-like growth factors (IGFs) have potent mitogenic and antiapoptotic effects on prostate epithelial cells. Through modulation of IGF bioactivity and other mechanisms, IGF-binding proteins (IGFBPs) also have growth-regulatory effects on prostate cells. Recently, IGF-I and IGFBP-3 have been implicated in prostate cancer risk among Western populations. To assess whether IGF-I, IGF-II, IGFBP-1, or IGFBP-3 are also associated with prostate cancer in a low-risk population, we measured plasma levels of these factors among 128 newly diagnosed prostate cancer cases and 306 randomly selected population controls in Shanghai, China. Relative to the lowest quartile of IGF-I levels, men in the highest quartile had a 2.6-fold higher prostate cancer risk, with a significant trend [odds ratio (OR) = 2.63; 95% confidence interval (95% CI) = 1.19-5.79; P(trend) = 0.01]. In contrast, men in the highest quartile of IGFBP-3 levels had a 46% decreased risk relative to the lowest quartile (OR = 0.54; 95% CI = 0.26-1.15; P(trend) = 0.08). A similar but less distinct result was observed for IGFBP-1 (OR = 0.60; 95% CI = 0.31-1.17; P(trend) = 0.25). Men in the highest quartile for the IGF-I:IGFBP-3 molar ratio (an indirect measure of free IGF-I) had a 2.5-fold higher risk compared with the lowest quartile (OR = 2.51; 95% CI = 1.32-4.75, P(trend) < 0.001). These associations were more pronounced after adjustment for serum 5alpha-androstane-3alpha,17beta-diol glucuronide and sex hormone-binding globulin levels. There was no significant association with IGF-II levels. Our findings in a low-risk population provide evidence that IGF-I, IGFBP-3, and IGFBP-1 are determinants of prostate cancer and indicate that additional studies are needed to evaluate their effects on ethnic and geographic incidence differentials and to elucidate carcinogenic mechanisms.
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PMID:Insulin-like growth factors and prostate cancer: a population-based case-control study in China. 1135 50

This study examined the diurnal variation in circulating total and free testosterone and sex hormone-binding globulin (SHBG) levels in young adult African American and Caucasian men in order to investigate whether there are differences in the secretion of these plasma hormones in populations at different risks of developing prostate cancer as they age. A significant and similar diurnal rhythm for total and free testosterone was found for both groups. Serum levels of total testosterone were 29.4% and 23.9% lower at 8:00 PM than at 8:00 AM in African American and Caucasian men, respectively. Significantly higher serum levels of total testosterone (P<.01) and SHBG (P <.02) were found in the African American than in the Caucasian men in both the morning and evening, whereas free testosterone levels were similar in both groups. The higher SHBG levels appear to have an environmental/metabolic basis in that the waist circumference, waist-to-hip ratio, and fasting insulin concentration were lower (P <.05) in African Americans than in Caucasians. In summary, these data indicate that racial differences in central adiposity in men are established in early adulthood and influence circulating SHBG and thereby testosterone levels. In light of the findings by others that SHBG increases cyclic adenosine monophosphate (cAMP) production in the prostate and that cAMP-dependent protein kinase A is a coactivator of the androgen receptor, these studies provide a possible mechanism by which circulating androgens may contribute to the increased risk for prostate cancer among African American men.
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PMID:Testosterone, sex hormone-binding globulin, and body composition in young adult African American and Caucasian men. 1158 1

Measurement of obesity is not as simple as its definition. Currently, several methods of measuring obesity are used in clinical studies. Skinfold thickness, crude weight, lean body mass (LBM), body mass index (BMI), and waist-to-hip ratio (WHR) are some of the more popular methods, but each contains its inherent strengths and flaws. In general, the results of the largest studies on prostate cancer and obesity have not been conclusive. One of the largest studies found an inverse relation to prostate cancer in the youngest age groups. The age and duration of obesity or any rapid changes in weight gain, along with other unhealthy exposures, may have some relation to prostate cancer incidence and mortality. Early intrinsic or extrinsic exposure to estrogen or estrogenlike compounds may provide a protective effect. The timing and duration of a higher estrogen and/or lower testosterone exposure may have a beneficial or detrimental impact on the prognosis of an established prostate tumor. Negative exposures over time such as low levels of sex hormone-binding globulin (SHBG), a greater exposure to growth factors, elevated insulin levels, greater sympathetic activity, higher cholesterol levels, immune system dysfunction, inadequate diets, smoking status, and other factors may be associated with an increased risk of prostate cancer and other diseases. Obesity may also be associated with other cancers for similar and different reasons. For example, morbidity and mortality from postmenopausal breast cancer, colon, kidney, and other cancers are potentially associated with obesity. Other comorbidities such as cataracts, coronary heart disease, diabetes, erectile dysfunction, hypertension, and others are also associated with obesity. The 2 largest prospective studies on BMI and overall mortality have also demonstrated the substantial negative impact of excess weight on society. Prostate cancer risk and obesity need further research to establish if a true association exists, but at this time, does it really matter? Overall, the profound adverse effect of being obese on general health is dramatic, and this is what clinicians and patients need to remember.
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PMID:Is obesity a risk factor for prostate cancer, and does it even matter? A hypothesis and different perspective. 1193 35

Soy beans contain high levels of the isoflavones genistein and daidzein and their glycosides and have been implicated in the prevention of prostate cancer, possibly via their effects on sex hormone metabolism. The aim of this study was to assess the relation between dietary soy intake and sex hormone levels in a cross-sectional analysis of 696 men with a wide range of soy intakes. Soy milk intake was measured using a validated semiquantitative food frequency questionnaire, and serum hormone concentrations were measured by immunoassay. Multiple regression was used to investigate the association between soy milk intake, an index of isoflavone intake, and hormone levels after adjustment for pertinent confounders. Soy milk intake was not associated with serum concentrations of testosterone, free testosterone, androstanediol glucuronide, sex hormone-binding globulin, or luteinizing hormone. These results suggest that soy milk intake, as a marker of isoflavone intake, is not associated with serum sex hormone concentrations among free-living Western men.
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PMID:Soy milk intake in relation to serum sex hormone levels in British men. 1209 27

Serum testosterone concentration appears to be higher in black men than white men, particularly at younger ages. The higher incidence of prostate cancer in blacks has been attributed, at least in part, to this difference. Other factors associated with androgen levels in men include age and obesity. However, most of the studies of adult androgen levels are limited by their cross-sectional design. We conducted longitudinal analyses (Generalized Estimating Equation) of the associations of age, body mass index (BMI), and waist circumference with total and free testosterone and sex hormone-binding globulin (SHBG) concentrations during an 8-year period and compared these hormonal factors between black (n = 483) and white (n = 695) male participants of the Coronary Artery Risk Development in Young Adults (CARDIA) Study. For men ages 24 years and older at the time of the first hormone measurement, increasing age was associated with a statistically significant decrease in serum total and free testosterone and an increase in SHBG (P < 0.05). BMI and waist circumference were inversely associated with total testosterone and SHBG, but only BMI was inversely associated with free testosterone. After adjustment for age and BMI, total testosterone was higher in blacks (0.21 ng/ml; P = 0.028) than whites, an approximately 3% difference. However, after further adjustment for waist circumference, there was no black-white difference (0.05 ng/ml; P = 0.62). These results indicate that the age-associated decrease in circulating testosterone and increase in SHBG begin during the 3rd decade of life, and that increasing obesity, particularly central obesity, is associated with decreasing total testosterone and SHBG. Results also suggest that the previously observed difference in total testosterone between black and white men could be attributed, for the most part, to racial differences in abdominal obesity.
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PMID:Serum androgen concentrations in young men: a longitudinal analysis of associations with age, obesity, and race. The CARDIA male hormone study. 1237 5

To examine the effect of estradiol (E(2)) without the confounding effect of hypothalamic-pituitary feedback, we studied men with prostate cancer in whom gonadotropin secretion was suppressed by LH-releasing hormone agonists (LHRH-A). Fourteen men over 65 yr of age and receiving established LHRH-A treatment (EST group) without bony metastases and 12 men who received LHRH-A as neoadjuvant therapy for locally advanced prostate cancer (NEO group) were randomized (double blind) to receive either 1 mg/d micronized E(2) (n = 12) or placebo (PL; n = 13) for 9 wk. E(2), estrone, testosterone, SHBG, PTH, and 25-hydroxy- and 1,25-dihydroxyvitamin D levels as well as markers of bone resorption [N- and C-telopeptide cross-links (NTX and CTX) and deoxypyridinoline] and bone formation (bone-specific alkaline phosphatase, osteocalcin, and N-terminal type I collagen) were measured before LHRH-A in the NEO group, before [baseline (BL)] and after 9 wk of E(2) or PL in all patients, and 6 wk after E(2) treatment in the EST group. In the NEO group, hormone levels fell 3 wk after the initial LHRH-A injection, and deoxypyridinoline increased significantly (P = 0.006). At BL, the EST group had higher bone turnover due to the longer duration of LHRH-A treatment. With E(2) treatment, E(2) levels rose into the normal male range, and two resorption markers decreased significantly from BL by 33% for NTX (P < 0.001) and 28% for CTX (P = 0.009). Bone formation markers did not change. PTH increased by 43% from BL (P < 0.01) in the E(2) group and decreased 16% from BL in the PL group (P < 0.01). Ionized calcium did not change in the E(2) group, but increased in the PL group by 2.3% (P < 0.01). NTX and CTX increased 6 wk after E(2) withdrawal in the EST group. We conclude that E(2) inhibits bone resorption in hypogonadal men through a direct skeletal effect that is independent of PTH. Low dose estrogen may be an option for the prevention and/or treatment of bone loss in this population.
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PMID:The effect of micronized estradiol on bone turnover and calciotropic hormones in older men receiving hormonal suppression therapy for prostate cancer. 1241 49

Insulin resistance and compensatory hyperinsulinaemia are thought to be the underlying factors in the metabolic or insulin-resistance syndrome and can be controlled by diet and exercise. Hyperinsulinaemia has been shown to have a direct effect on the live, suppressing the production of sex hormone-binding globulin (SHBG) and insulin-like growth factor-binding proteins 1 and 2 (IGFBP-1, -2) while stimulating the production of insulin-like growth factor 1 (IGF-1). These factors have been proposed to be important modulators of hormone-related cancers, such as prostate cancer. Men adopting a low-fat diet and daily exercise reduced their levels of serum insulin and IGF-1, while increasing their levels of IGFBP-1 and sex hormone-binding globulin (SHBG). Cell-culture studies with LNCaP prostate cancer cells showed apoptosis of tumour cells and a reduction in serum-stimulated cell growth in the post diet and exercise serum. These results suggest that prostate cancer may be another aspect of the insulin-resistance syndrome and that adopting a low-fat diet combined with regular exercise may reduce the risk for prostate and other hormone-related cancers. This needs to be tested with prospective studies.
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PMID:Prostate cancer: another aspect of the insulin-resistance syndrome? 1245 75

We present a review of the epidemiological evidence for relations of prostate cancer risk to circulating total and bioavailable androgens, to alterations in the metabolism of insulin-like growth factor-1 (IGF-1), and to anthropometric indices of longitudinal growth (body stature) and overweight. In addition, we review the physiological inter-relationships between insulin, growth hormone/IGF-1 axis, and sex steroid metabolism, as well as the associations of bioavailable sex steroid levels with overweight and obesity. A first conclusion of this review is that, taken together, epidemiological studies have provided little support for the hypothesis that prostate cancer risk is increased in men with elevated total or biovailable testosterone (T). Although one prospective study showed an increased risk in men with low plasma sex hormone-binding globulin (SHBG) and with elevated plasma T for given levels of SHBG, this was not confirmed by results from other cohort studies. A second conclusion is that overweight, which is generally associated with moderate reductions in both total and bioavailable plasma T, appears to be unrelated to any significant increase or decrease in prostate cancer risk. However, significant increases in risk have been observed for men with a taller body stature, or with elevated plasma IGF-1. IGF-1 may directly enhance prostate tumorigenesis by inhibiting apoptosis and by stimulating cell proliferation. In addition, IGF-1 downregulates the synthesis of SHBG, and enhances sex steroid synthesis. Therefore, we do not entirely rule out that due to an elevation of plasma IGF-1 levels, men at increased risk of prostate cancer also have mildly elevated plasma bioavailable T, which epidemiological studies may have failed to demonstrate because of methodological problems. Prostate Cancer and Prostatic Diseases (2000) 3, 157-172
Prostate Cancer Prostatic Dis 2000 Nov
PMID:Plasma androgens, IGF-1, body size, and prostate cancer risk: a synthetic review. 1249 92

Because high waist-to-hip ratio (WHR) and high serum insulin levels have been reported to be associated with an increased risk of prostate cancer, we assessed the relationship between insulin resistance and prostate cancer risk in Chinese men. We measured fasting serum glucose and insulin levels in 128 case and 306 control subjects and used the homeostasis model assessment to derive indices of insulin sensitivity and resistance. Relative to men in the lowest tertiles, men in the highest tertile of insulin sensitivity had a reduced risk of prostate cancer (odds ratio [OR] = 0.35, 95% confidence interval [CI] = 0.21 to 0.60), but men in the highest tertile of insulin resistance had an increased risk of prostate cancer (OR = 2.78, 95% CI = 1.63 to 4.72). Considering insulin resistance and WHR together, the effect of insulin resistance was apparent in all tertiles of WHR, with men in the highest tertile of insulin resistance and WHR having the highest risk (OR = 8.21, 95% CI = 2.84 to 23.70). The associations between prostate cancer risk and insulin sensitivity or resistance were independent of total caloric intake and serum levels of insulin-like growth factors, sex hormones, and sex hormone-binding globulin. Because of the retrospective design of this study, the role of insulin resistance in prostate cancer needs to be confirmed in prospective studies.
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PMID:Insulin resistance and prostate cancer risk. 1286 55

Despite strong indirect evidence that androgens stimulate prostate cancer development, data from most analytical studies on this association have been negative. To further investigate this issue, we studied the interrelationships between androgenicity and insulin-like growth factor I (IGF-I), insulin and leptin. Within a prospective cohort study, we measured testosterone, sex hormone-binding globulin (SHBG) and IGF-I, IGF-binding protein (IGFBP)-1, IGFBP-3, insulin and leptin, in plasma from 149 cases and 298 controls. Testosterone correlated positively with SHBG, whereas testosterone and SHBG correlated inversely with IGF-I, IGFBP-3, insulin, leptin and body mass index (BMI). Indices of free testosterone showed an inverse linear correlation with leptin (P<0.01), and a strong drop in the 5th quintile of BMI. However, levels of free testosterone showed non-linear relationships over quintiles of insulin and IGF-I, with a significant increase in the second quintile of IGF-I compared with other levels. The absence of an association between plasma levels of androgens and prostate cancer risk in analytical studies, despite the strong indirect evidence of their tumour-stimulating effects, may reflect the complex and mostly inverse associations of androgenicity to IGF-I, insulin and leptin which are hormones that have also been implicated as risk factors for prostate cancer.
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PMID:Interrelationships between plasma testosterone, SHBG, IGF-I, insulin and leptin in prostate cancer cases and controls. 1288 84


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