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 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent evidence indicates that obesity and related metabolic abnormalities are associated with increased incidence or mortality for a number of cancers, including those of the colon, prostate, and pancreas. Obesity, physical inactivity, visceral adiposity, hyperglycemia, and hyperinsulinemia are relatively consistent risk factors for colon cancer and adenoma. Also, patients with type 2 diabetes mellitus have a higher risk of colon cancer. For prostate cancer, the relationship to obesity appears more complex. Obesity seems to contribute to a greater risk of aggressive or fatal prostate cancer but perhaps to a lower risk of nonaggressive prostate cancer. Furthermore, men with type 2 diabetes mellitus are at lower risk of developing prostate cancer. Long-standing type 2 diabetes increases the risk of pancreatic cancer by approximately 50%. Furthermore, over the past 6 years, a large number of cohort studies have reported positive associations between obesity and pancreatic cancer. Together with data from prediagnostic blood specimens showing positive associations between glucose levels and pancreatic cancer up to 25 years later, sufficient evidence now supports a strong role for diabetes and obesity in pancreatic cancer etiology. The mechanisms for these associations, however, remain speculative and deserve further study. Hyperinsulinemia may be important, but the role of oxidative stress initiated by hyperglycemia also deserves further attention.
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PMID:The role of obesity and related metabolic disturbances in cancers of the colon, prostate, and pancreas. 1749 13

Increasing prevalence of obesity in many parts of the world emphasizes the importance of learning more about the relationship between obesity and prostate cancer (PC). The present paper reviews the impact of obesity on PC using knowledge obtained from the available literature. Search of published literature in PUBMED database. Adipose tissue constitutes an active endocrine and metabolic organ which may be relevant in the development and progression of PC by different potential mechanisms. Furthermore, obesity could have an impact on the outcome of different treatment modalities for PC, both functionally as anatomically. Obesity is a growing problem, however, the exact role in the development and progression of PC has not been elucidated. Regarding the optimal treatment of PC in obese patients, comparative prospective studies are needed.
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PMID:The impact of obesity on prostate cancer. 1753 26

IGF-1 and IGFBP-3 may influence risk of prostate cancer through their roles in cellular growth, metabolism and apoptosis, however, epidemiologic results have been inconsistent. The role of obesity in prostate cancer risk is not clearly understood, but hyperinsulinemia-related increases in bioactive IGF-1 levels, associated with obesity, could be a component of the relationship between the IGF-axis and prostate cancer. We conducted a nested case-control study in the prospective Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial to examine associations between IGF-1 and IGFBP-3 and risk of prostate cancer. A total of 727 incident prostate cancer cases and 887 matched controls were selected for this analysis. There was no clear overall association between IGF-1, IGFBP-3 and IGF-1:IGFBP-3 molar ratio (IGFmr) and prostate cancer risk, however, IGFmr was associated with risk in obese men (BMI > 30, p-trend = 0.04), with a greater than 2-fold increased risk in the highest IGFmr quartile (OR 2.34, 95% CI 1.10-5.01). Risk was specifically increased for aggressive disease in obese men (OR 2.80, 95% CI 1.11-7.08). In summary, our large prospective study showed no overall association between the insulin-like growth factor axis and prostate cancer risk, however, IGFmr was related to risk for aggressive prostate cancer in obese men.
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PMID:IGF-1 and IGFBP-3: Risk of prostate cancer among men in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. 1759 8

The skeleton is the most common site of metastasis in patients with advanced prostate cancer. Despite many advances in targeting skeletal metastases, the mechanisms behind the attraction of prostate cancer cells to the bone are not known. Osteoclast cathepsin K, due to its ability to effectively degrade bone matrix collagen I, has been implicated in colonization and growth of prostate tumours in the bone. Identification of new cathepsin K substrates in the bone microenvironment and the recent findings demonstrating its involvement in obesity and inflammation suggest additional roles for this enzyme in skeletal metastases of prostate cancer.
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PMID:Cathepsin K in the bone microenvironment: link between obesity and prostate cancer? 1763 27

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

Genome-wide association studies provide a new and powerful approach to investigate the effect of inherited genetic variation on the risk of human disease. These studies rely on high throughput DNA microarray technology to genotype hundreds of thousands of genetic variants across the human genome. The first genome-wide association studies have identified previously unknown genetic risk factors that influence a range of diseases, including prostate cancer, breast cancer, myocardial infarction, age-related macular degeneration, diabetes, Crohn's disease and obesity. Many more studies are currently underway, including a number that will focus on other cancers (e.g., colorectal). Here we discuss the major issues involved in conducting genome-wide association studies and how these studies can be used to examine cancer phenotypes.
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PMID:Genome-wide association studies of cancer. 1766 17

It has long been known that obesity modestly increases the risk of prostate cancer mortality. Only recently, however, have studies examined whether this association is due to an increased risk of aggressive disease and/or worse outcomes following initial diagnosis and treatment. This distinction is important, because if obesity increases the risk of metastasis and death following treatment, weight loss could be an effective adjunct treatment. We now have good evidence that obesity increases the risk of aggressive prostate cancer, but reduces the risk of low-grade, nonaggressive cancer. In addition, several studies have found that obesity increases the risk of biochemical recurrence following prostatectomy; however, the few studies that have examined more definitive end points, metastases and death, have been less consistent. Furthermore, there are no studies that have examined whether weight loss after diagnosis favorably affects prostate cancer outcome. While accepting the current limitations in our knowledge base, it is our opinion that it is appropriate for physicians to counsel their patients to lose weight following prostate cancer diagnosis and motivate this change in behavior by emphasising the likely benefit of improving long-term outcome.
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PMID:Obesity and prostate cancer mortality. 1792 21

A model of the origin of modern humans through several population bottlenecks caused by glacial cycles and cold-arid periods was used as a frame for describing occurrence of unique physiological characteristics. Occurrence of regular evening food sharing among the hominid group members improved their chances of finding food the next day. It allowed slow emergence of a gracile and energy efficient phenotype. Improving chances of group survival in the harsh environment included these traits: - The menstrual cycle occurrence in the common ancestor of human and great apes. - Single pregnancies only in women with sufficient fat reserves. Ovulations stop during the food shortage seasons, or longer periods of starvation and during lactation. - Women prone to obesity sooner become pregnant, passing the obesity trait as an advantage. - Seldom pregnancies separated by several years of anovulation made a strong pressure toward the longevity of women and man. - Menopausis improved the group survival through preventing pregnancy of women to old to deliver and raise children without significant risks. The modern times food abundance results in high incidences of adiposity, diabetes and metabolic syndrome. Continuos ovulations from puberty to menopausis except during seldom pregnancies and lactations is considered responsible for the occurrence of estrogen induced breast and endometrial cancers. The combination of longevity with decades of androgen secretion is the main cause of prostate cancer.
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PMID:Human adiposity, longevity and reproduction features as consequences of population bottlenecks. 1797 25

The prevalence of both obesity and prostate cancer are increasing in the US. Recently, there has been keen interest in the relationship between obesity and the biology of cancers, including prostate cancer. This article reviews the current literature regarding body mass index (BMI) and its relationship with various clinical aspects of prostate cancer, including its incidence, screening, diagnosis and treatment. Despite several biological mechanisms that potentially link obesity to prostate cancer, the effects of obesity on serum PSA levels and prostate volume, and the subsequent effects on the detection of prostate cancer, are not consistent according to the available literature. Additionally, the epidemiologic data for the incidence of prostate cancer in obese and non-obese populations are conflicting. Treatment of prostate cancer in obese populations is problematic, but data on the ability to overcome these difficulties are unclear. It is difficult to determine whether oncologic and functional outcomes in obese patients differ substantially from those in non-obese patients. Separating the contributions of technical issues from potentially different tumor biologies is not currently possible. Hopefully, the increasing focus on these two highly prevalent health problems might further elucidate their complex relationship.
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PMID:The effect of body mass index on PSA levels and the development, screening and treatment of prostate cancer. 1798 37

Anorexia and weight loss are part of the wasting syndrome of late-stage cancer, are a major cause of morbidity and mortality in cancer, and are thought to be cytokine mediated. Macrophage inhibitory cytokine-1 (MIC-1) is produced by many cancers. Examination of sera from individuals with advanced prostate cancer showed a direct relationship between MIC-1 abundance and cancer-associated weight loss. In mice with xenografted prostate tumors, elevated MIC-1 levels were also associated with marked weight, fat and lean tissue loss that was mediated by decreased food intake and was reversed by administration of antibody to MIC-1. Additionally, normal mice given systemic MIC-1 and transgenic mice overexpressing MIC-1 showed hypophagia and reduced body weight. MIC-1 mediates its effects by central mechanisms that implicate the hypothalamic transforming growth factor-beta receptor II, extracellular signal-regulated kinases 1 and 2, signal transducer and activator of transcription-3, neuropeptide Y and pro-opiomelanocortin. Thus, MIC-1 is a newly defined central regulator of appetite and a potential target for the treatment of both cancer anorexia and weight loss, as well as of obesity.
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PMID:Tumor-induced anorexia and weight loss are mediated by the TGF-beta superfamily cytokine MIC-1. 1798 62


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