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• W2053790199 abstract "Background Aberrant arachidonic acid metabolism by 12-lipoxygenase (12-LOX) and cyclooxygenase-2 (COX-2) has been implicated in human carcinogenesis. Inherited polymorphisms in 12-LOX and COX-2 contributed to differential expression or activity of these enzymes might confer interindividual susceptibility to cancer. Objective To examine the functional significance of 12-LOX 261 Arg> Gln polymorphism and its association, alone and in combination with COX-2 −1195G > A and −765G > C polymorphisms, with risk of developing esophageal squamous cell carcinoma (ESCC). Methods The platelet 12-LOX activity was measured by quantifying 12-HETE in the lipoxygenation reaction. Genotypes of 12-LOX261Arg>Gln and COX-2 −1195G>A and −765G>C polymorphisms were determined in a case-control study consisting of 1026 patients and 1270 controls. Associations with the risk of ESCC were estimated by logistic regression. Results Subjects with the 12-LOX Gln/Gln genotype had higher platelet 12-LOX activity (mean±SEM nmol/mg/min) than those with the Arg/Arg genotype (0.405±0.047 [n=10] versus 0.136±0.022 [n=6]; P=0.001). Genotyping data showed that the 12-LOX Gln/Gln genotype was associated with increased risk of developing ESCC (odds ratio [OR]=1.42, 95% confidence interval [CI]=1.12–1.81), compared with the Arg/Arg genotype adjusted for sex, age, and smoking. An increased risk of ESCC was also associated with the COX-2 −1195GA (OR=1.34, 95% CI=1.08–1.68; P=0.008), −1195AA (OR=1.72, 95% CI=1.35–2.20; P=<0.001), and −765GC (OR=2.24, 95% CI=1.59–3.16; P<0.001) genotypes. Furthermore, a multiplicative interaction between the 12-LOX Gln/Gln and COX-2 −1195AA or −765GC genotype in intensifying risk of ESCC was observed, with the ORs for the presence of both 12-LOX Gln/Gln and COX-2 −1195AA or −765GC genotypes being 3.21 (95% CI=1.93–5.34) and 3.33 (95% CI=1.59–6.98). A multiplicative interaction between the −765GC genotype and smoking was also evident (OR=4.45, 95% CI=2.71–7.29). Conclusion These observations suggest that inherited polymorphisms in arachidonic acid-metabolizing enzymes, which result in heightened gene expression or enzymatic activity, may confer host susceptibility to ESCC." @default.
• W2053790199 created "2016-06-24" @default.
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• W2053790199 date "2007-03-01" @default.
• W2053790199 modified "2023-10-11" @default.
• W2053790199 title "Platelet 12-lipoxygenase Arg261Gln polymorphism: functional characterization and association with risk of esophageal squamous cell carcinoma in combination with COX-2 polymorphisms" @default.
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• W2053790199 doi "https://doi.org/10.1097/fpc.0b013e328010bda1" @default.
• W2053790199 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/17460548" @default.
• W2053790199 hasPublicationYear "2007" @default.
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