Tumor markers and rectal cancer: support for an inflammation-related pathway.
Inflammation may be a key element in the etiology of colorectal cancer. In our study, we examine associations between factors related to inflammation and specific rectal cancer mutations. A population-based study of 750 rectal cancer cases with interview and tumor DNA were compared to 1,205 population-based controls. Study participants were from Utah and the Northern California Kaiser Permanente Medical Care Program. Tumor DNA was analyzed for TP53 and KRAS2 mutations and CpG Island methylator phenotype. We assessed how these tumor markers were associated with use of anti-inflammatory drugs, polymorphisms in the IL6 genes (rs1800795 and rs1800796) and dietary antioxidants. Ibuprofen-type drugs, IL6 polymorphisms (rs1800796) and dietary alpha-tocopherol and lycopene significantly altered likelihood of having a TP53 mutation. This was especially true for TP53 transversion mutations and dietary antioxidants (OR for beta-carotene 0.51 95% CI 0.27, 0.97, p trend 0.03; alpha-tocopherol 0.41 95% CI 0.20, 0.84, p trend 0.02) Beta-carotene and ibuprofen significantly altered risk of KRAS2 tumors. The associations between lutein and tocopherol and TP53 and KRAS2 mutations were modified by IL6 genotype. These results suggest that inflammation-related factors may have unique associations with various rectal tumor markers. Many factors involved in an inflammation-related pathway were associated with TP53 mutations and some dietary factors appeared to be modified by IL6 genotype.
Slattery
Martha L
ML
Department of Medicine, University of Utah, Salt Lake City, UT 84108, USA. marty.slattery@hsc.utah.edu
Wolff
Roger K
RK
Herrick
Jennifer
J
Caan
Bette J
BJ
Samowitz
Wade
W
D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000235:genetics*; D002140:California / Q000453:epidemiology; D002338:Carotenoids / Q000494:pharmacology; D016022:Case-Control Studies; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000032:analysis; D005247:Feeding Behavior; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007052:Ibuprofen / Q000494:pharmacology; D007249:Inflammation / Q000150:complications / Q000235:genetics*; D015850:Interleukin-6 / Q000235:genetics*; D000077276:Lycopene; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D012004:Rectal Neoplasms / Q000097:blood / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics* / Q000517:prevention & control*; D012307:Risk Factors; D018426:SEER Program; D024505:Tocopherols / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D014589:Utah / Q000453:epidemiology; D018631:ras Proteins / Q000235:genetics*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D015850:Interleukin-6; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D002338:Carotenoids; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D024505:Tocopherols; D001241:Aspirin; D000077276:Lycopene; D007052:Ibuprofen