title: Association of common polymorphisms in inflammatory genes interleukin (IL)6, IL8, tumor necrosis factor alpha, NFKB1, and peroxisome proliferator-activated receptor gamma with colorectal cancer.
abstract: 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 alpha (-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.
authors.affiliation: International Agency for Research on Cancer, 69372 Lyon, France [S. L., L. G-P., F. C.].
authors.forename: Stefano
authors.initials: S
authors.lastname: Landi
authors.forename: Victor
authors.initials: V
authors.lastname: Moreno
authors.forename: Lydie
authors.initials: L
authors.lastname: Gioia-Patricola
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Guino
authors.forename: Matilde
authors.initials: M
authors.lastname: Navarro
authors.forename: Javier
authors.initials: J
authors.lastname: de Oca
authors.forename: Gabriel
authors.initials: G
authors.lastname: Capella
authors.forename: Federico
authors.initials: F
authors.lastname: Canzian
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D003110:Colonic Neoplasms / Q000453:epidemiology / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D015850:Interleukin-6 / Q000235:genetics*; D016209:Interleukin-8 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D012004:Rectal Neoplasms / Q000453:epidemiology / Q000235:genetics*; D012307:Risk Factors; D013030:Spain / Q000453:epidemiology; D014157:Transcription Factors / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D015850:Interleukin-6; D016209:Interleukin-8; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha