Prostate UK - Prostate news article

Prostate news article, June 2007

IS OBESITY A RISK FACTOR FOR PROSTATE CANCER?

Miles Goldstraw, Peter Amoroso, Professor Roger S Kirby

Obesity is reaching epidemic proportion affecting over 30% of the population in the United States [1] and becoming a growing problem Worldwide. While obesity has recognised links with a variety of chronic disease states including diabetes, hypertension and cardiovascular disease it may be a factor in the aetiology of prostate cancer. However, attempting to identify obesity as a risk factor from other related factors such as dietary intake, socio-economic status and genetic susceptibility is extremely difficult necessitating multivariate analysis of large scale epidemiological studies. Therefore, whether obesity is a causal factor or merely associated with prostate cancer is a matter of continued debate. Confirmation of a link could have enormous implications for prostate cancer management and quality of life issues.

The precise biological processes linking obesity and prostate cancer are unknown, however there are a number of possible mechanisms proposed. Obesity is associated with several hormonal alterations including lower levels of sex hormone-binding globulin that may increase the fraction of biologically available testosterone. Certainly androgens have been implicated as a potential cause of prostate cancer and endocrine aberrations may play a role in progression to clinically significant disease. Obesity is associated with diabetes, the metabolic syndrome with insulin resistance and hyperinsulinaemia: exposure to elevated levels of insulin and circulating insulin-growth factor-one (IGF-1) may facilitate prostate cancer progression. Increased levels of leptin, decreased levels of adiponectin and increased dietary saturated fats may all be of importance. The mitogenic effects of leptin on cancer cells, in combination with increased expression of growth factors may be more likely to contribute to the progression of prostate cancer. Therefore, obesity associated with high leptin levels should be considered a risk factor in prostate cancer patients [2]. Mistry et al. suggested 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 [3]. Any or all of these factors may play a part in prostate cancer initiation and/or prostate cancer progression.

There is accumulating evidence that high dietary fat intake may be associated with prostate cancer risk [4] with some studies suggesting a high intake of red meat may promote development of a more aggressive disease. However, while higher fat intake and obesity are clearly linked the same cannot be said for obesity and prostate cancer incidence. Large scale epidemiological studies show conflicting results on any potential link. One recent case-controlled study from the US [5] examined men aged 40-64 and noted an inverse association between BMI and prostate cancer risk: they reported that men with BMI >29kg/m2 had the lowest risk of prostate cancer with an odds ratio of 0.77 (95% CI 0.56-1.06). Giovanucci et al. [6] agreed with this inverse association performing a large prospective longitudinal study of >51,000 men aged 40-75 years of age commenting that men <60 years of age and a BMI ≥27.5kg/m2 were approximately half as likely to be diagnosed with prostate cancer. This latter study was unusual in that BMI as a predictor for prostate cancer was mutually adjusted for confounding factors such as height, history of diabetes, physical activity and dietary intake (including red meat and processed meat). In stark contrast, perhaps the largest study into BMI and prostate cancer incidence involved 950000 Norwegian men followed up for an average of 21years [7]: results demonstrated a modest positive correlation with an increased RR of 1.09 (95% CI 1.29-1.94) for obese men (BMI ≥30) compared with normal weighted men. Sub-group analysis did identify that in the age group 50-59 the RR increases to 1.58 (95% CI 1.29-1.94) indicating BMI may have a greater role in younger men.

These results are somewhat confusing and at first glance appear to suggest a null association between obesity and overall prostate cancer risk. Confounding factors include inherent problems with study design, and inability to stratify for other risk factors. Irani et al. [8] attempted to counter many of these confounding factors by comparing 194 cases of prostate cancer with an equal number of those with BPH: results noted that BMI was not significantly associated with prostate cancer when compared to BPH but in general obese men had 2.5 times the risk of having prostate cancer. Another study by Scales et al. examined a representative sample of 57,827 men 40 years or older and concluded that obese men are more likely than normal weight men to be screened for prostate cancer [9]. However, in contrast it may be the case that obese men have lower levels of PSA which could mask biologically significant prostate cancer [10].

Perhaps more convincing is the association between obesity and the risk of advanced prostate cancer and prostate cancer mortality. One comprehensive analysis retrospectively studied 135,006 Swedish construction workers [11] with an 18-year average follow-up: results demonstrated a non-significant positive correlation between BMI and prostate cancer incidence however, more importantly a strong association between mortality and BMI was discovered with an increased RR of 1.4 (95% CI 1.09-1.81) for BMI >26.2 kg/m2 in comparison to normal (BMI <22.1 kg/m2). This suggests that obese men with prostate cancer may have biologically more aggressive disease. Support for this theory is provided by recent data on men who are undergoing radical prostatectomy for early stage prostate cancer [12,13]. Amling et al. [12] evaluated the impact of BMI on men undergoing radical prostatectomy: results demonstrated that BMI was an independent predictor of higher Gleason score and biochemical recurrence. The apparent contradiction that obesity affects prostate cancer mortality while not affecting prostate cancer incidence suggests obesity may differentially regulate prostate cancer progression rather than tumour initiation. Freedland et al. argue the point quite convincingly that obesity may affect the development of non-aggressive versus aggressive prostate cancer differently [14].

In conclusion, the precise association between obesity and prostate cancer is not clear. Large scale epidemiological studies have failed to find conclusive evidence of an associated increased incidental risk. More recent data may suggest a role in tumour progression with the development of a more aggressive phenotype. Significantly, a recent study by Rodriguez et al. suggests that men who lose weight may reduce the risk of prostate cancer death [15]. It is important that health professionals play a role in encouraging individuals to participate in practical and simple dietary changes with fitness education as they improve overall longevity and quality of life. The profound adverse effect of obesity on general health is dramatic. Dietary modification, matched with recommendations for the prevention of cardiovascular and other chronic diseases, are desirable.

References

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