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Fibrates and Risk of Cancer in Tissues with High PPAR-α Concentration: A Nested Case–Control Study

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Abstract

Background

Fibrates are lipid-lowering agents that act as peroxisome proliferator-activated receptor (PPAR)-α agonists. They have been associated with cancers in experimental models, but data in humans are rare, and among published studies none has investigated cancers in tissues with high PPAR-α concentrations.

Methods

A nested case–control study was performed in a French population-based healthcare database. Adults aged ≥45 years, and free of cancer for 3 years, were followed for 5 years for incident cases of melanoma, non-melanoma skin cancers, thyroid, pancreas, bladder, and kidney cancers. Cases were matched with up to ten controls for age, sex, and diseases that could increase the risk of cancers. Conditional logistic models, adjusted for drug-use as potential confounders, were used to estimate the risk (odds ratio [OR]) of cancers of interest (and individual cancers) associated with cumulative exposure to fibrates (defined daily doses [DDD]).

Results

Among the 147,338 eligible subjects, 3,331 (2.3 %) cases of studied cancers were identified. Only use of fibrates >550 DDDs was associated with an increased risk (OR 1.26; 95 % CI 1.12–1.42), and similar results were found for statins (≥1,460 DDDs; OR 1.15; 95 % CI 1.03–1.28). When considering cancers individually, the association was significant for non-melanoma skin-cancer (OR 1.35; 95 % CI 1.14–1.60), and close to significance for bladder cancer (OR 1.26; 95 % CI 0.96–1.64); similar associations with the use of statins were found.

Conclusions

The associations found between fibrate exposure and cancers of tissues with high PPAR-α concentrations were most likely related to residual confounding as similar associations were found for statins.

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Acknowledgments

Francesco Salvo and Antoine Pariente had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. They agree to allow the journal to review their data if requested.

This study was supported by the French IReSP (Institut de la Recherche en Santé Publique) through a grant obtained after the 2011 Call for Research, which was part of the Plan Cancer 2009–2013. The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, or approval of the manuscript.

Conflicts of interest declaration

Fabienne Bazin, Aude Kostrzewa, Christian Bandre, and Philip Robinson, have had no relationships with companies that might have an interest in the submitted work in the previous 3 years. Francesco Salvo is a consultant of YOLARX Consultants Inc. (Montreal, Canada), and has worked on studies concerning one antifungal, one anticancer drug, and paracetamol. Bernard Bégaud has received investigator-initiated research funding from the French Health Ministry (2011); he is chair of the scientific committee for two pharmacoepidemiological studies conducted by the contract research organisation LA-SER (London, UK)—one on medicines used in osteoarthritis, the other on the use of homeopathic remedies by French practitioners. Nicholas Moore, in the previous 3 years, has had specified relationships on other matters with the following drug companies that might have an interest in the submitted work: Pfizer, Servier, Pierre Fabre, Roche, Merck Serono, Novartis, AstraZeneca, Abbott, Axcan, Bristol-Myers Squibb, Celgene, Cephalon, Vivatec, Lundbeck, GlaxoSmithKline, Leo Pharma, Helsinn Healthcare, Orion, Genevrier, Takeda, Sanofi, and Johnson & Johnson; he has also had, in the previous 3 years, specified relationships on other matters with public regulatory agencies and with healthcare insurance systems that might have an interest in the submitted work. Antoine Pariente, in the previous 3 years, has had specified relationships on other matters with Novartis that might have an interest in the submitted work. The authors’ spouses, partners, or children have no financial relationships that may be relevant to the submitted work. All authors have no non-financial interests that may be relevant to the submitted work.

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Authors and Affiliations

  1. Univ Bordeaux, Bordeaux, France

    Francesco Salvo, Nicholas Moore, Bernard Bégaud & Antoine Pariente

  2. INSERM U657, Bordeaux, France

    Francesco Salvo, Nicholas Moore, Bernard Bégaud & Antoine Pariente

  3. CHU Bordeaux, Bordeaux, France

    Francesco Salvo, Aude Kostrzewa, Christian Bandre, Nicholas Moore & Antoine Pariente

  4. ADERA, Bordeaux, France

    Fabienne Bazin & Philip Robinson

  5. INSERM 1401 CIC, Bordeaux, France

    Fabienne Bazin, Philip Robinson, Nicholas Moore, Bernard Bégaud & Antoine Pariente

  6. Université de Bordeaux, INSERM U657, 146, Rue Léo Saignat, Bâtiment 1A Zone nord Site Carreire, BP36, 33076, Bordeaux, CEDEX, France

    Francesco Salvo

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  1. Francesco Salvo
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Correspondence to Francesco Salvo.

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Salvo, F., Bazin, F., Kostrzewa, A. et al. Fibrates and Risk of Cancer in Tissues with High PPAR-α Concentration: A Nested Case–Control Study. Drug Saf 37, 361–368 (2014). https://doi.org/10.1007/s40264-014-0157-8

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