title: Study of the polymorphisms of cyclooxygenase-2 (-765G>C) and 5-lipoxygenase (1708G>A) in patients with colorectal cancer.
abstract: Colorectal cancer (CRC) is the fourth most common cause of cancer-related mortality worldwide. Genetic alterations have been associated with an increased risk of cancer and greater tumor aggressiveness. Cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) genes are important in cell cycle regulation, tumor growth and prostaglandin synthesis. The aim of the present study was to investigate the association between polymorphisms in the COX-2 and 5-LOX genes and the risk of CRC. A case-control study was conducted in patients with CRC matched for gender and age to a control group. DNA was extracted from peripheral leukocytes, and the polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism and gene sequencing. A specific questionnaire was applied to evaluate smoking, excessive alcohol consumption, physical activity, non-steroidal anti-inflammatory drug use and meat, fiber and fat intake. A total of 185 patients with CRC and 146 controls were studied. The heterozygous GC genotype of the COX-2 gene polymorphism was the most common in the two groups (60.0% in CRC patients and 52.7% in controls). The CC genotype was associated with an increased risk of CRC (odds ratio, 3.63; 95% confidence interval, 1.31-10.1; P=0.013). The homozygous wild-type genotype of the 5-LOX gene polymorphism was detected in 72.4% of the CRC patients and in 71.2% of the control subjects. The homozygous mutant genotype (CC) of the COX-2 gene is an independent risk factor for CRC. No association was found between 5-LOX genotypes and CRC.
authors.affiliation: Gastroenterology Division, Federal University of São Paulo, São Paulo 04023900, Brazil.
authors.forename: Célia Aparecida Marques
authors.initials: CA
authors.lastname: Pimenta
authors.affiliation: Gastroenterology Division, Federal University of São Paulo, São Paulo 04023900, Brazil.
authors.forename: Flavia Roche Moreira
authors.initials: FR
authors.lastname: Latini
authors.affiliation: Gastroenterology Division, Federal University of São Paulo, São Paulo 04023900, Brazil.
authors.forename: Jacqueline Miranda
authors.initials: JM
authors.lastname: DE Lima
authors.affiliation: Gastroenterology Division, Federal University of São Paulo, São Paulo 04023900, Brazil.
authors.forename: Tiago Donizetti
authors.initials: TD
authors.lastname: DA Silva
authors.affiliation: Gastroenterology Division, Federal University of São Paulo, São Paulo 04023900, Brazil.
authors.forename: Aledson Vitor
authors.initials: AV
authors.lastname: Felipe
authors.affiliation: Gastroenterology Division, Federal University of São Paulo, São Paulo 04023900, Brazil.
authors.forename: Vanessa Maria
authors.initials: VM
authors.lastname: DE Lima Pazine
authors.affiliation: Gastroenterology Division, Federal University of São Paulo, São Paulo 04023900, Brazil.
authors.forename: Nora Manoukian
authors.initials: NM
authors.lastname: Forones
keywords: cancer; colorectal; cyclooxygenase; lipoxygenase; polymorphism