Epidemiology
Tumor markers and rectal cancer: Support for an inflammation-related pathway
Martha L. Slattery,
Roger K. Wolff,
Jennifer Herrick,
Bette J. Caan,
Wade Samowitz,
Corresponding Author
Martha L. Slattery
Department of Medicine, University of Utah, Salt Lake City, UT
Department of Medicine, University of Utah, Salt Lake City, UT 84108, USASearch for more papers by this authorRoger K. Wolff
Department of Medicine, University of Utah, Salt Lake City, UT
Search for more papers by this authorJennifer Herrick
Department of Medicine, University of Utah, Salt Lake City, UT
Search for more papers by this authorBette J. Caan
Division of Research, Kaiser Permanente Medical Research Center, Oakland, CA
Search for more papers by this authorWade Samowitz
Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, UT
Search for more papers by this authorMartha L. Slattery,
Roger K. Wolff,
Jennifer Herrick,
Bette J. Caan,
Wade Samowitz,
Corresponding Author
Martha L. Slattery
Department of Medicine, University of Utah, Salt Lake City, UT
Department of Medicine, University of Utah, Salt Lake City, UT 84108, USASearch for more papers by this authorRoger K. Wolff
Department of Medicine, University of Utah, Salt Lake City, UT
Search for more papers by this authorJennifer Herrick
Department of Medicine, University of Utah, Salt Lake City, UT
Search for more papers by this authorBette J. Caan
Division of Research, Kaiser Permanente Medical Research Center, Oakland, CA
Search for more papers by this authorWade Samowitz
Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, UT
Search for more papers by this authorAbstract
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. © 2009 UICC
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