Medication use and cancer risk
- Autores: Joan Fortuny Moya
- Directores de la Tesis: Manolis Kogevinas (dir. tes.)
- Lectura: En la Universitat Autònoma de Barcelona ( España ) en 2007
- Idioma: español
- Tribunal Calificador de la Tesis: Josep Maria Antó i Boqué (presid.), Rafael de Cid Ibeas (secret.), Joan-Ramon Laporte (voc.), Marina Pollán Santamaría (voc.), María Luisa Ibáñez Mora (voc.)
- Materias:
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- Resumen
The aim of the thesis was to evaluate the association between use of inflammation-related drugs and cancer risk. This PhD thesis includes five manuscripts derived from four epidemiological studies.
Bladder cancer studies. The bladder cancer case control study "Epicuro" was conducted in Spain. Two manuscripts were published based on this study. The first one showed that in Spain the chronic use of aspirin and paracetamol was low (8% users of aspirin and 5% users of paracetamol) compared to that of the US or Northern Europe. Differences in drug use related to sociodemographic variables were observed. The second article showed that regular use of non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs) related to a decreased risk of bladder cancer (OR= 0.4, 95%CI= 0.2-0.9). Polymorphisms in the NSAID metabolism-related CYP2C9 gene did not modify this inverse association. No evidence was found of an overall effect related to use of aspirin (AAS) or paracetamol. However, paracetamol was associated to an increased bladder cancer risk (OR=1.8, 95%CI= 0.9-3.6) among subjects with a genetically determined poor capacity of eliminating paracetamol's toxic metabolite (N-acetyl-p-benzoquinone-imine, NAPQI). For the Epicuro study we developed a drug exposure matrix to automatically and accurately recode the reported brand names into active ingredients and doses. In a second bladder cancer study, conducted in New Hampshire, USA, we found an increased risk of bladder cancer among long term users of phenacetin (OR= 3.0, 95%CI= 1.4-6.5). In this study, use of paracetamol was associated with a decreased risk of bladder cancer, especially among long-term users and non-invasive, low grade, TP53 negative tumors. We also found that the use of NSAIDs was associated to a significantly decreased risk of bladder cancer, specifically for AAS use (OR= 0.5, 95%CI= 0.3-.8). The association with NSAIDs was particularly strong among invasive, high grade and TP53 positive tumors. A drug exposure
