Prostate Cancer


positive energy balance and thus promote increased fat storage and obesity.15


and pre-adipocyte differentiation was observed.24,25


However, the main cause of obesity in developed countries is a decrease in energy expenditure which is primarily due to decreased physical activity in conjunction with an energy-dense diet.


Obesity is considered as one of the greatest long-term health threats for humans in both developed and developing countries.4


Worldwide,


2.8 million people, about 8 % of total deaths due to non-communicable diseases, die each year as a result of being overweight. Obesity is undoubtedly related to several diseases and disabilities; moreover, an independent association between obesity and all-cause mortality has been demonstrated in adults.16,17


The risks of coronary heart disease,


ischaemic stroke and type 2 diabetes mellitus increase steadily with increasing BMI, defined as weight (kg)/height2 (m2), a measure widely used in epidemiological and clinical studies for the definition of obesity. Based on BMI, the general population can be classified as follows: underweight (less than 18.5), normal weight (18.5–24.9), overweight (25–29.9) and obese (30 or greater). The increase in obesity prevalence has suggested further dividing obesity into three classes: class I obesity (30–34.9), class II obesity (35–39.9) and morbid obesity (40 and greater). BMI offers a very useful operational definition for many contexts, but authors are beginning to question whether the field should adopt a more useful operational definition.18


BMI is an


imperfect measure in the elderly population because of the age- dependent decrease in height and lean body mass. It was suggested that fat distribution may be more important than BMI in assessing disease risk associated with obesity, especially among older adults.19 Thus, as an alternative to BMI, it was proposed to measure abdominal obesity by waist circumference or waist:hip circumference ratio (WHR). A waist circumference of 102 cm in a man is defined as having excess abdominal fat, even if the man’s BMI is normal. A high waist measurement has been demonstrated to be a better independent risk factor for chronic diseases, particularly for adults with a BMI between 25 and 34.9.20


Waist circumference also appears to be a more adequate measure, because fat mass and fat tissue distribution change dramatically throughout life. In old age, fat is redistributed from subcutaneous to intra-abdominal visceral depots as well as other ectopic or less frequent sites, including bone marrow, muscle and the liver. In consequence, more fat is lost from subcutaneous than visceral fat depots after middle age. However, also considering the limitation of BMI measurement in older men, a recent meta-analysis approach has suggested that elevated BMI is associated with a risk of PCa-specific mortality in prospective cohort studies and biochemical recurrence in PCa patients.21


Normally, adipose tissue undergoes significant age-related changes in both quantity and composition. Age-related fat tissue dysfunction may be related to a combination of mechanisms, with reduced capacity to store lipotoxic fatty acids, fat tissue damage by fatty acids and inflammation being contributing factors. These processes are interrelated and amplify each other. Studies conducted in centenarians have demonstrated that one of the key factors for maintaining health and longevity is the preservation of a well-functioning adipose tissue. Cumulative dysregulation of multiple adipokines, including an elevation of pro-inflammatory cytokines, constituted a strong marker of poor prognosis among centenarians.22


At a cellular level, although new fat cells are formed throughout life, and pre-adipocyte numbers also increase or remain stable in various fat deposits with ageing,23


48 A reduced


capacity of pre-adipocytes to express differentiation-dependent proteins that bind cytotoxic fatty acids and convert them into less cytotoxic triglycerides with ageing may, in turn, diminish defence against lipotoxicity, setting up a vicious cycle that accelerates pre-adipocyte and fat tissue dysfunction.26


As in obesity, perhaps also


Recent reports show that pro-inflammatory cytokines and chemokines are expressed predominantly in pre-adipocytes, rather than in adipocytes.28,29


However, fat tissue inflammation with


ageing appears to be caused by changes in both pre-adipocytes and macrophages. Dysfunctional pre-adipocytes release more pro-inflammatory cytokines and chemokines that induce macrophage recruitment and activation. Importantly, an in vivo study has demonstrated that ageing is sufficient to modify the profile of adipose tissue macrophages towards a pro-inflammatory environment.30


Thus


the fat tissue deregulation that occurs in ageing and obesity may initiate self-propagating inflammatory cycles.


Obesity and Prostate Cancer


Migrant studies have clearly demonstrated that environmental factors and lifestyle may explain the geographical variation in cancer incidence. Epidemiological data are concordant in suggesting that PCa rates of Asian immigrants in the US significantly increase with respect to those in their homelands.31,32


One of the largest


geographical disparities in incidence among cancers is observed in PCa; incidence differs 60-fold between US and Chinese men. However, the observation that Chinese- and Japanese-Americans have rates that are much higher than their counterparts in China and Japan supports a role for environmental rather than genetic factors.33 Among the underlying risk factors present in immigrant countries, overweight and obesity account for 15–20 % of all cancer deaths.34


In


the last years of the past century a large increase in cancer incidence in low-risk countries has been reported, independently from an improvement in diagnosis methods.35,36


Such increases are concurrent


with westernisation in these populations, suggesting that changes in the prevalence of certain common potential risk factors, such as dietary fat, obesity and physical activity, may have contributed at least in part to the progression and rising rates of PCa.37,38


Genetic factors have been invoked to explain the higher incidence rates reported for African-Americans with respect to white Americans, but also in this case available data about population-based incidence rates in Africa, although incomplete and scarcely comparable, indicate much lower incidence rates than the rates reported for African-Americans.33


In addition to ageing, the aetiology of sporadic PCa is very heterogeneous. However, data on other risk factors, such as circulating levels of hormones, physical activity, body size, smoking, drinking, sexual behaviour and occupational exposures, are conflicting.39


a decline in capacity for lipid accumulation


Pca is a slow-growing cancer with a long latency period. The prevalence of latent tumours has been shown to be quite high in the elderly population, affecting about 50 % of men over the age of 70.40


Thus cancer-promoting factors may significantly change the EUROPEAN ONCOLOGY & HAEMATOLOGY


with ageing, cross-talk among different cell types in fat tissue leads to a pro-inflammatory state that may contribute to systemic metabolic dysfunction. It is known that ageing is accompanied by chronic low-grade inflammation as stated by two- to fourfold increases in serum levels of inflammatory markers. This condition is independent of pre-existing morbidity, and its causal factors are not very well understood.27


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