The Metabolic Syndrome and Risk of Prostate Cancer in Italy
Introduction
Several definitions of the metabolic syndrome (MetS) have been proposed 1, 2, 3, 4. Efforts have been made to fix a common set of diagnostic criteria, with the aim to allow international comparisons (5). These efforts led to a joint statement of several scientific associations that defined the MetS as the presence of three out of five of the following factors: Elevated waist circumference, elevated triglycerides, reduced high-density lipoprotein (HDL) cholesterol, increased blood pressure, and increased fasting glucose (5).
The prevalence of the MetS is increasing worldwide, together with the interest of the scientific community on its effects on various health outcomes (6), including prostate cancer (7). In fact, although we could not find any epidemiologic investigation published before 2004 (8), at least nine studies on the issue have been made available in the last few years 9, 10, 11, 12, 13, 14, 15, 16, 17. Most investigations were conducted in the United States or in Nordic countries, whereas data from other populations are scanty. Further, findings were largely inconsistent, owing at least in part to different study design, definition of MetS, and outcome (i.e., mortality or incidence) used in different investigations. Two prospective investigations from Northern Europe, one from Finland (8), and one from Norway (13) found an increased risk of prostate cancer. The Finnish study, using the modified World Health Organization definition of the MetS (18), found a relative risk (RR) of 1.94 [95% confidence interval (CI), 1.06–3.53] for men with MetS at baseline, whereas the Norwegian study, based on four MetS components, reported a RR of 1.56 (95% CI, 1.21–2.00). Another analysis from Finland, based on the Helsinki Heart Study which focused on three out of the five components of the MetS, reported an odds ratio (OR) of 3.36 (95% CI, 1.19–9.44) in men with all three components (17). An U.S. case-control study including 637 prostate cancer cases found ORs of 1.71 (95% CI, 0.97–3.01) in African Americans and 1.02 (95% CI, 0.64–1.62) in white men with MetS, defined using a modified version of the Adult Treatment Panel (ATP) III criteria (10). On the other hand, no significant association emerged in cohort studies from Norway (RR, 0.91; 95% CI, 0.77–1.09, MetS defined using ATP III criteria) (14), Japan (RR, 0.76; 95% CI, 0.47–1.22, American Heart Association/National Heart, Lung, and Blood Institute criteria) (11) and the United States (RR, 1.32; 95% CI, 0.63–2.77, ATP III criteria) (12), as well as in an Italian study that linked data from archives of pharmaceutical prescriptions to local Cancer Registries (standardized incidence ratio, 0.93; 95% CI, 0.75–1.14, for subjects prescribed antihypertensive, hypoglycemic, and hypolipemic drugs) (15). Conversely, in the U.S. Atherosclerosis Risk in Communities Study, including 385 cases of prostate cancer, a significant inverse association was found with MetS (defined using ATP III criteria, RR, 0.77; 95% CI, 0.60–0.98) (16).
With the aim to provide further information on the issue from the Mediterranean area, we examined data from an Italian case-control study on risk factors for prostate cancer. Traditional dietary habits of this area, namely, the Mediterranean diet, could reduce the prevalence of the MetS by improving endothelial functions and lowering insulin resistance 19, 20.
Section snippets
Methods
Data were derived from a case-control study of prostate cancer conducted between 1991 and 2002 in the greater Milan area, in the provinces of Pordenone and Gorizia in northern Italy, in the province of Latina in central Italy, and in the urban area of Naples in southern Italy (21). Cases were 1294 men (median age, 66 years; range, 46–74) admitted with incident, histologically confirmed prostate cancer to a network of teaching and general hospitals in the study areas. Controls were 1451 patients
Results
Table 1 gives the distribution of 1294 cases of prostate cancer and 1451 controls, and the corresponding ORs and 95% CI, according to age and selected characteristics. Compared with controls, cases were more educated, reported a lower level of occupational physical activity at age 30, a higher nonalcohol energy intake, and had a family history of prostate cancer more often than controls. Alcohol consumption and smoking habits were similar in cases and controls.
Table 2 shows the distribution of
Discussion
Hypercholesterolemia was the only component of the MetS associated with prostate cancer in this study, confirming previous studies on the issue 26, 27, 28, 29, whereas diabetes, hypertension, and abdominal obesity showed no significant association. Therefore, a major issue was whether the findings observed in this study for the MetS itself, indicating a positive relation with prostate cancer, were meaningful or were merely explained by the association with hypercholesterolemia. When we examined
Conclusions
The MetS was positively associated with the risk of prostate cancer in this population. Men with the MetS had a 66% higher risk compared with those without, and the risk increased with the number of components of the syndrome up to a 4-fold elevated risk for men reporting the presence of all four factors considered in this study in combination.
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This work was supported by the Italian Association for Cancer Research (project No. 10068) and the Italian League against Cancer.