Journal Article

Associations of functional polymorphisms in <i>cyclooxygenase-2</i> and platelet 12-lipoxygenase with risk of occurrence and advanced disease status of colorectal cancer

Wen Tan, Jianxiong Wu, Xuemei Zhang, Yongli Guo, Junniao Liu, Tong Sun, Bailin Zhang, Dan Zhao, Ming Yang, Dianke Yu and Dongxin Lin

in Carcinogenesis

Volume 28, issue 6, pages 1197-1201
Published in print June 2007 | ISSN: 0143-3334
Published online December 2006 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgl242
Associations of functional polymorphisms in cyclooxygenase-2 and platelet 12-lipoxygenase with risk of occurrence and advanced disease status of colorectal cancer

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Aberrant arachidonic acid metabolism by cyclooxygenase (COX)-2 and 12-lipoxygenase (LOX) has implicated in carcinogenesis. Genetic polymorphisms in COX-2 and 12-LOX might therefore affect susceptibility to colorectal cancer (CRC). To examine this hypothesis, genotypes of COX-2 –1290A>G, –1195G>A, –765G>C and 12-LOX 261Arg>Gln polymorphisms were determined in 1000 CRC patients and 1300 controls. Increased risk of developing CRC was associated with the COX-2 –1195GA [adjusted odds ratio (OR) = 1.24, 95% confidence interval (CI) = 1.00–1.54] and –1195AA (adjusted OR = 1.77, 95% CI = 1.38–2.25) genotypes compared with the –1195GG genotype. Similarly, the increased risk for CRC was also associated with the COX-2 –765GC genotype (adjusted OR = 1.73, 95% CI = 1.23–2.43) compared with the –765GG genotype. Consistent with the results of genotype analyses, the ORs for the A_1195-C_765-containing haplotypes were significantly higher than those for the G_1195-G_765-containing haplotypes (P < 0.01). Furthermore, the –1195A allele was further associated with advanced CRC, with adjusted ORs of Dukes D CRC against Dukes A CRC being 2.43 (95% CI = 1.15–4.97) and 2.66 (95% CI = 1.23–5.74) for the –1195GA and –1195AA genotypes, respectively. The increased risk of CRC was also associated with the 12-LOX 261Gln/Gln genotype compared with the Arg/Arg genotype (adjusted OR = 1.38, 95% CI = 1.09–1.74). Together, these observations indicate that inherited polymorphisms in arachidonic acid-metabolizing enzymes may confer susceptibility to CRC.

Journal Article.  4303 words. 

Subjects: Clinical Cytogenetics and Molecular Genetics

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