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Epidemiology and Prevention |
, NFKB1, and Peroxisome Proliferator-activated Receptor 
with Colorectal Cancer1 ,,2
International Agency for Research on Cancer, 69372 Lyon, France [S. L., L. G-P., F. C.]; Dipartimento di Scienze dell’Uomo e dell’Ambiente, Universita’ di Pisa, 56100 Pisa, Italy [S. L.]; Institut Catala d’Oncologia, Barcelona, Spain [V. M., E. G., M. N., G. C.]; and Digestive Surgery Service, Ciudad Sanitaria i Universitaria de Bellvitge, University of Barcelona, Barcelona, Spain [J. O.]
Animal models and epidemiological observations suggest that a continuous inflammatory condition predisposes to colorectal cancer (CRC), but the roles of different elements participating in inflammatory responses have been little investigated in relation to CRC. We have studied the association between single nucleotide polymorphisms in the interleukin (IL)-6 (-174 G>C), IL8 (-251T>A), tumor necrosis factor 
(-308G>A), and PPARG (Pro12Ala) genes and the risk of CRC in a group of 377 cases and 326 controls from Barcelona, Spain. These genes are known to be important for inflammation of the colorectum and common allelic variants have been shown to have a biological effect. The PPARG Ala12 and IL8-251A genotypes are associated with reduced risk of disease (0.56, 95% CI, 0.37–0.85, P = 0.0056, and 0.70, 95% CI, 0.50–0.99, P = 0.043, respectively), whereas the IL6–174C genotype is associated with increased risk (1.53, 95% CI, 1.12–2.09, P = 0.0073). We also studied a single nucleotide polymorphism in intron 11 of the NFKB1 gene (rs1020759), which probably lacks any functional role, and found no significant association with the disease. This is the first report that IL6, IL8, and PPARG genes are important in relation to inflammation-related risk of sporadic CRC.
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