title: Associations of functional polymorphisms in cyclooxygenase-2 and platelet 12-lipoxygenase with risk of occurrence and advanced disease status of colorectal cancer.
abstract: 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.
authors.affiliation: Department of Etiology and Carcinogenesis, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Tan
authors.forename: Jianxiong
authors.initials: J
authors.lastname: Wu
authors.forename: Xuemei
authors.initials: X
authors.lastname: Zhang
authors.forename: Yongli
authors.initials: Y
authors.lastname: Guo
authors.forename: Junniao
authors.initials: J
authors.lastname: Liu
authors.forename: Tong
authors.initials: T
authors.lastname: Sun
authors.forename: Bailin
authors.initials: B
authors.lastname: Zhang
authors.forename: Dan
authors.initials: D
authors.lastname: Zhao
authors.forename: Ming
authors.initials: M
authors.lastname: Yang
authors.forename: Dianke
authors.initials: D
authors.lastname: Yu
authors.forename: Dongxin
authors.initials: D
authors.lastname: Lin
mesh_terms: D000368:Aged; D001092:Arachidonate 12-Lipoxygenase / Q000097:blood* / Q000235:genetics* / Q000502:physiology; D001792:Blood Platelets / Q000201:enzymology*; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000235:genetics* / Q000502:physiology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012720:Severity of Illness Index
chemical_list: D001092:Arachidonate 12-Lipoxygenase; D051546:Cyclooxygenase 2