title: Polymorphisms in arachidonic acid metabolism-related genes and the risk and prognosis of colorectal cancer.
abstract: Cyclooxygenase-2 (COX-2), 12-lipoxygenase (12-LOX) and phospholipaseA2 (PLA2) played important roles in the modulation of apoptosis, angiogenesis, carcinogenesis and invasion of colorectal cancer (CRC). The polymorphisms in COX-2, 12-LOX and PLA2 may affect their roles. Therefore, we investigated if COX-2 -1195G > A, 12-LOX 261Arg > Gln and PLA2 c.349 + 191A > G polymorphisms were associated with risk and prognosis of CRC as well as possible interactions with the environmental factors on the risk of CRC in Northeast of China. A case-control study with 451 cases and 631 controls were carried out, a cohort with 386 patients were followed up. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Compared with the 261Arg/Arg genotype, 12-LOX 261Arg/Gln genotype and 261Arg/Gln + Gln/Gln genotypes reduced the risk of rectal cancer by 33% (adjusted OR = 0.67, 95% CI 0.47-0.97, p = 0.03) and 32% (adjusted OR = 0.68, 95% CI 0.49-0.96, p = 0.03), respectively. The adjusted HR for the association between 12-LOX 261Gln/Gln genotype and overall survival in patients with CRC was 1.68 (95% CI 1.06-2.68, p = 0.03). There was also evidence of an interaction between the PLA2 c.349 + 191 A > G genotypes and the overnight food consumption (adjusted ORi = 1.92, 95% CI 1.14-3.25, P(interaction) = 0.01). These observations indicate that 12-LOX 261Arg > Gln polymorphism may affect risk of rectal cancer, and it may be a potential predictive marker for prognosis of CRC.
authors.affiliation: Department of Epidemiology, Public Health College, Harbin Medical University, 157, Baojian Street, Nangang District, Harbin, Heilongjiang Province, People's Republic of China.
authors.forename: Shuying
authors.initials: S
authors.lastname: Li
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Zhao
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Wu
authors.forename: Ye
authors.initials: Y
authors.lastname: Li
authors.forename: Lin
authors.initials: L
authors.lastname: Zhu
authors.forename: Binbin
authors.initials: B
authors.lastname: Cui
authors.forename: Xinshu
authors.initials: X
authors.lastname: Dong
authors.forename: Suli
authors.initials: S
authors.lastname: Tian
authors.forename: Fulan
authors.initials: F
authors.lastname: Hu
authors.forename: Yashuang
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D016824:Antigens, Human Platelet / Q000235:genetics*; D001092:Arachidonate 12-Lipoxygenase / Q000235:genetics*; D016718:Arachidonic Acid / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000235:genetics*; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000209:etiology*; D051546:Cyclooxygenase 2 / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D012307:Risk Factors
chemical_list: D016824:Antigens, Human Platelet; D014408:Biomarkers, Tumor; C083451:human platelet antigen 1b; D016718:Arachidonic Acid; D001092:Arachidonate 12-Lipoxygenase; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human