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Insulin resistance is inversely related to prostate cancer: a prospective study in Northern Sweden
Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
German Cancer Research Center, Germany.
International Agency for Research on Cancer, France.
International Agency for Research on Cancer, France.
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2007 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 120, no 12, 2678-2686 p.Article in journal (Refereed) Published
Abstract [en]

Factors related to insulin resistance have been implicated in prostate cancer development, however, few analytical studies support such an association. We performed a case control study on 392 prostate cancer cases and 392 matched controls nested in a prospective cohort in Northern Sweden. Plasma concentrations of C-peptide, leptin, glycated haemoglobin (HbA1c) and fasting and post-load glucose were analysed and homeostatic model assessment of insulin resistance (HOMA-IR) was calculated. Conditional logistic regression analyses were used to calculate odds ratios (OR) of prostate cancer. High levels of C-peptide, HOMA-IR, leptin and HbA1c were associated with significant decreases in risk of prostate cancer, with ORs for top vs. bottom quartile for C-peptide of 0.59 (95% Confidence Interval [CI], 0.40-0.89; ptrend = 0.008), HOMA-IR 0.60 (95% CI, 0.38-0.94; ptrend = 0.03), leptin 0.55 (95% CI, 0.36-0.84; ptrend = 0.006) and HbA1c 0.56 (95% CI, 0.35-0.91; ptrend = 0.02). All studied factors were strongly inversely related to risk among men less than 59 years of age at blood sampling, but not among older men, with a significant heterogeneity between the groups for leptin (pheterogeneity = 0.006) and fasting glucose (pheterogeneity = 0.03). C-peptide and HOMA-IR were strongly inversely related to non-aggressive cancer but were non-significantly positively related to risk of aggressive disease (pheterogeneity = 0.007 and 0.01, respectively). Our data suggest that androgens, which are inversely associated with insulin resistance, are important in the early prostate cancer development, whereas insulin resistance related factors may be important for tumour progression.

Place, publisher, year, edition, pages
John Wiley & Sons, 2007. Vol. 120, no 12, 2678-2686 p.
Keyword [en]
prostatic neoplasms, insulin resistance, blood glucose, C-peptide, leptin
National Category
Cancer and Oncology
Research subject
Epidemiology
Identifiers
URN: urn:nbn:se:umu:diva-22551DOI: 10.1002/ijc.22587ISI: 000245873000020PubMedID: 17278097OAI: oai:DiVA.org:umu-22551DiVA: diva2:217096
Available from: 2009-05-13 Created: 2009-05-13 Last updated: 2017-12-13Bibliographically approved
In thesis
1. Metabolic factors and cancer risk: prospective studies on prostate cancer, colorectal cancer, and cancer overall
Open this publication in new window or tab >>Metabolic factors and cancer risk: prospective studies on prostate cancer, colorectal cancer, and cancer overall
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: A large number of prospective studies have shown that overweight and diabetes are related to an increased risk of many cancers, including colorectal cancer. In contrast, diabetes has been related to a decreased risk of prostate cancer, and overweight has been related to an increased risk of fatal, but not of incident, prostate cancer. Data from studies on metabolic factors related to overweight and diabetes, and the association with cancer risk, are limited.

 Aim: The aim of this thesis was to study metabolic factors in relation to risk of prostate cancer (paper I and III), colorectal cancer (paper II and V), and cancer overall (paper VI).

 Methods: Study designs were i) case-control studies, nested within the Northern Sweden Health and Disease Cohort (paper I and II), and ii) cohort studies of the Swedish Construction Workers cohort (paper III), and the Metabolic syndrome and Cancer project (Me-Can) comprising seven European cohorts (paper V and VI). Paper IV was a descriptive paper of Me-Can.

 Results, prostate cancer: In paper I, increasing levels of several factors related to insulin resistance (insulin, insulin resistance index, leptin, HbA1c, and glucose) were associated with a decreased risk of overall incident prostate cancer, and the associations were stronger for non-aggressive tumours. In paper III, increasing levels of blood pressure was associated with a significant decreased risk of overall incident prostate cancer and of non-aggressive tumours. Body mass index (BMI) was significantly positively related to fatal prostate cancer. 

 Results, colorectal cancer: In paper II, obesity, hypertension, and hyperglycaemia, were associated with an increased risk of colorectal cancer, and presence of two or three of these factors was associated with a higher risk than the presence of one single factor. In paper V, BMI was associated with a significant linear positive association with risk of colorectal cancer in men and women, and significant positive associations were also found in men for blood pressure and triglycerides. A high metabolic syndrome score, based on levels of BMI, blood pressure, glucose, cholesterol, and triglycerides, was associated with a significant increased risk of colorectal cancer in men and women. The association was stronger than for any of the factors in single, but there was no evidence of a positive interaction between these metabolic factors.

 Results, cancer overall: Blood glucose was significantly positively associated with risk of incident and fatal cancer overall, and at several specific sites. The associations were stronger in women than in men, and for fatal than for incident cancer.

 Conclusions: Results from these studies indicate that elevated blood glucose is related to an increased risk of cancer overall and at several specific sites, and further, that overweight and metabolic aberrations increase the risk of colorectal cancer in an additive way. The association with prostate cancer seems to be more complex; insulin resistance and high blood pressure were in our studies related to a decreased risk of overall incident prostate cancer and of non-aggressive tumours, whereas overweight increased the risk of fatal prostate cancer.

Place, publisher, year, edition, pages
Umeå: Institutionen för kirurgi och perioperativ vetenskap, 2009. 90 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1267
National Category
Urology and Nephrology
Research subject
Epidemiology
Identifiers
urn:nbn:se:umu:diva-22567 (URN)978-91-7264-784-8 (ISBN)
Distributor:
Urologi och andrologi, 901 85, Umeå
Public defence
2009-06-05, Sal B, byggnad 1 D, Umeå Universitetssjukhus, Umeå, 13:15 (English)
Opponent
Supervisors
Available from: 2009-05-19 Created: 2009-05-13 Last updated: 2010-03-26Bibliographically approved

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