Annals of Oncology Advance Access originally published online on April 12, 2006
Annals of Oncology 2006 17(6):1014-1017; doi:10.1093/annonc/mdl080
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© 2006 European Society for Medical Oncology
Self-reported history of hypercholesterolaemia and gallstones and the risk of prostate cancer
1 Istituto di Ricerche Farmacologiche ‘Mario Negri’, Milan, Italy; 2 Unità di Epidemiologia e Biostatistica, Centro di Riferimento Oncologico, Aviano (PN), Italy; 3 Servizio di Epidemiologia, Istituto Tumori ‘Fondazione Pascale’, Naples, Italy; 4 International Agency for Research on Cancer, Lyon Cedex, France; 5 Istituto di Statistica Medica e Biometria, Università degli Studi di Milano, Milan, Italy
* Correspondence to: Dr F. Bravi, Laboratorio di Epidemiologia, Istituto di Ricerche Farmacologiche ‘Mario Negri’, Via Eritrea 62-20157 Milan, Italy. Tel: +39-02-39014577; Fax: +39-02-33200231; E-mail: bravi{at}marionegri.it
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Abstract |
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 Top Abstract introductionpatients and methodsresultsdiscussionReferences |
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Background: Although prostate cancer is one of the most common male cancers, its aetiology—and particularly the role of comorbidity—remains poorly understood.
Patients and methods: Between 1991 and 2002, a case–control study on prostate cancer was conducted in Italy. This included 1294 men under the age of 75 years with incident, histologically confirmed prostate cancer, and 1451 controls, admitted to the same hospitals as cases for a wide spectrum of acute, non-neoplastic diseases. The subjects' self-reported history of selected medical conditions was assessed through a structured and satisfactorily reproducible questionnaire. Multivariate odds ratios (ORs) and 95% confidence intervals (CIs) were obtained after allowance for major potential confounding factors.
Results: A significant direct relation was observed between hypercholesterolaemia and prostate cancer (OR = 1.51, 95% CI 1.23–1.85). This association was stronger (OR = 1.80) in older subjects (age 
65) than in younger ones (OR = 1.32). A non-significant excess risk of prostate cancer was also observed for gallstones (OR = 1.26, 95% CI 0.93–1.70) and the relation was apparently stronger in patients with lower body mass index (OR = 1.59).
Conclusions: This study suggests a possible relation between hypercholesterolaemia and prostate cancer.
Key words: case–control study, cholesterol, medical history, prostate cancer
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introduction |
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TopAbstractintroductionpatients and methodsresultsdiscussionReferences |
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Prostate cancer is one of the most common male cancers and its incidence has been increasing in most countries [1
], although recent patterns have been influenced by the widespread use of the prostrate-specific antigen (PSA) test. However, apart from the established role of age, ethnicity and family history [2–4], its aetiology remains poorly understood.
Some medical conditions, such as diabetes mellitus [5–8], obesity [9, 10] and cardiovascular conditions [11–15] have been associated with prostate cancer risk in previous investigations, although the results were not consistent. A possible association between hypercholesterolaemia and prostate cancer has been suggested [16], but the evidence is limited.
In the present paper, we specifically investigated the role of hypercholesterolaemia and gallstones on the risk of prostate cancer and considered the relation with other medical conditions, using data from a large case–control study conducted in Italy. Results on diabetes were shown in a previous publication of our group [8].
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patients and methods |
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TopAbstractintroductionpatients and methodsresultsdiscussionReferences |
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Data were obtained from a case–control study on prostate cancer, conducted between 1991 and 2002 in four Italian areas, including the greater Milan area, the provinces of Pordenone and Gorizia in northern Italy, the province of Latina in central Italy and the urban area of Naples in southern Italy [9
]. Cases were 1294 men under the age of 75 years (median age 66, range 46–74 years) with incident histologically confirmed prostate cancer, diagnosed within 1 year before interview, admitted to major teaching and general hospitals in the areas under surveillance. Controls were 1451 men aged less than 75 years (median age 63, range 46–74) admitted to the same hospitals as cases for a wide spectrum of acute, non-neoplastic conditions, unrelated to known or potential risk factors for prostate cancer, as well as to other chronic conditions. Among the controls, 21% were admitted for traumas, 32% for other orthopaedic disorders, 17% for acute surgical conditions and 29% for various other illnesses. Less than 5% of subjects contacted refused to participate and the response rate did not change among hospitals or geographical areas. All cases and controls were interviewed in hospital by trained interviewers, using a structured questionnaire, including information on socio-demographic factors, anthropometric variables, lifestyle habits (such as tobacco smoking and alcohol consumption), a food frequency section and family history of cancer. The section on patients' medical history included a self-reported history of about 10 non-malignant conditions, including hypercholesterolaemia and gallstones, and the corresponding age at first diagnosis or treatment.
Odds ratios (OR) and the corresponding 95% confidence intervals (CI) were estimated using unconditional multiple logistic regression models, including terms for current age (quinquennia), study centre, years of education (<7, 7–11, 12), body mass index (BMI, approximate quintiles), occupational physical activity at 30 years (active, moderately active, inactive), alcohol intake (abstainer or ex-drinker, current drinker <14 drinks/week, 14–21 drinks/week, 21–35 drinks/week, 35 drinks/week), tobacco smoking (never smoker, ex-smoker, current smoker) and family history of prostate cancer in first-degree relatives.
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results |
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Table 1 shows the distribution of cases and controls, according to history of hypercholesterolaemia and gallstones, and the corresponding ORs. After allowance for major confounding factors, a direct association was observed between prostate cancer and hypercholesterolaemia (OR = 1.51, 95% CI 1.23–1.85, P < 0.0001). An excess risk of prostate cancer, although not significant, was also observed for gallstones (OR = 1.26, 95% CI 0.93–1.70). Similar increased risks were found according to age at first diagnosis of hypercholesterolaemia and gallstones.
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Table 2 gives the ORs of prostate cancer for hypercholesterolaemia and gallstones in strata of age at prostate cancer diagnosis, BMI, histological grade (Gleason score) and pathological stage (TNM). In older subjects (age
65) the direct association with hypercholesterolaemia was stronger (OR = 1.80) than in younger ones (OR = 1.32), although the risk estimates were not significantly heterogeneous. No meaningful differences were observed according to age for gallstones. In patients with lower BMI, the direct association between gallstones and prostate cancer was apparently stronger (OR = 1.59) than in heavier patients (OR = 1.08), while no meaningful differences were observed for hypercholesterolaemia across strata of BMI. No relevant differences were observed for both hypercholesterolaemia and gallstones across strata of histological grade or pathological stage.
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Table 3 shows the distribution of cases and controls according to the other conditions investigated, including diabetes, obesity, hypertension, allergy, esophagitis, gastro-duodenal ulcer, intestinal polyps and various thyroid conditions. None of these showed any meaningful association with prostate cancer risk.
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discussion |
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TopAbstractintroductionpatients and methodsresultsdiscussionReferences |
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The present study found a direct association between hypercholesterolaemia and prostate cancer, which has been only sporadically reported previously [16
]. This association was somewhat stronger for men with hypercholesterolaemia diagnosed before 50 years and in those older than 65 years. Gallstones—which are often related to hypercholesterolaemia—were also directly, although not significantly, associated to prostate cancer risk. To our knowledge, no previous studies reported any relation between gallstones and prostate cancer. Cholesterol is the major substrate for steroid hormone synthesis, including androgens; this suggests a possible link between prostate cancer and hypercholesterolaemia.
Laboratory data also suggested that statins may have chemopreventive potential against prostate cancer [17]. In support of this hypothesis, two case–control investigations reported an inverse relation between statins and prostate cancer [18, 19]. Moreover, a preliminary analysis of a cohort of airline pilots showed that individuals with hypercholesterolaemia tend to have higher serum PSA than those with normal serum cholesterol, and that treatment with statins may lower serum PSA, suggesting an indirect role of statins on prostate cancer, mediated by cholesterol action [18]. However, another two case–control studies did not find any association between statin use and prostate cancer [20, 21]. No information on statin use was available in our case–control study.
Despite the large dataset, a potential limitation of the present study is the relatively low number of patients affected and thus the low statistical power. Furthermore, information on the history of selected conditions was self-reported and could not be validated using medical records. Moreover, our study was hospital-based and hospital controls may differ from the general population in several aspects as regards medical history. However, we carefully excluded from the comparison group all the admission diagnoses known to be related to urologic or hormone-related conditions. Also, the use of controls with a wide spectrum of admission diagnosis and the consistency of the results across various diagnostic categories of controls, reassure against any major selection bias. With reference to recall bias and data quality, the same hospital setting for both cases and controls suggests that they are similarly sensitised towards recalling diseases that occurred in the past [22, 23]. Among other strengths of the study, there were the similar catchment areas of cases and controls, the almost complete participation, the satisfactory reproducibility of information on medical conditions [24] and the allowance for a large number of potential confounding factors, including education and family history of prostate cancer, which were directly related, and physical activity, which was inversely related to prostate cancer risk in this dataset [4, 9]. None of these, however, materially modified any of the results.
The significant association with hypercholesterolaemia may be a consequence of multiple testing; however, even after applying the conservative Bonferroni correction, the association remained statistically significant. The absence of association with about 10 other medical conditions investigated weights against significant over-reporting by cases and consequently indicates that the relation between hypercholesterolaemia and prostate cancer appears to be real.
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Acknowledgements |
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The authors thank Mrs I. Garimoldi for editorial assistance.
This work was conducted with the contribution of the Italian Association for Cancer Research, the Italian League Against Cancer and the Italian Ministry of Research (PRIN 2005).
Received for publication December 23, 2005. Revision received February 22, 2006. Accepted for publication March 1, 2006.
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