title: Polymorphisms in PTGS1, PTGS2 and IL-10 do not influence colorectal adenoma recurrence in the context of a randomized aspirin intervention trial.
abstract: Regular use of aspirin and other nonsteroidal antiinflammatory drugs reduces both the development of colorectal neoplasia and recurrence of colorectal adenoma (CRA). Modulation of the effects of aspirin by genetic factors has been reported, potentially allowing targeting of treatment to individuals most likely to gain benefit. Prostaglandin H synthase 1 (PTGS1) and PTGS2 are key enzymes in prostaglandin synthesis and are inhibited by aspirin, whilst interleukin-10 (IL-10) is an important antiinflammatory cytokine. We investigated whether functional genetic polymorphisms in the PTGS1, PTGS2 and IL-10 genes influence CRA recurrence in individuals participating in a randomized aspirin intervention trial. DNA was available for genotyping from 546 patients who received aspirin (300 mg daily) or placebo for a mean 41-months' duration. Homozygote carriers of variant alleles for the PTGS1 50C>T, PTGS2 -765G>C and IL-10 -592C>A polymorphisms did not have a significantly altered risk of CRA recurrence (relative risk [RR]=0.91; 95% confidence interval [CI]: 0.14-6.07, RR=1.32; 95% CI: 0.66-2.62 and RR=1.24; 95% CI: 0.74-2.07, respectively). There were also no significant interactions between aspirin intervention and genotype in determining recurrence risk. These data indicate that these polymorphisms are unlikely to influence CRA recurrence and cannot be used to identify individuals who derive benefit from aspirin intervention.
authors.affiliation: Section of Cancer Genetics, Institute of Cancer Research, Sutton SM2 5NG, United Kingdom.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Hubner
authors.affiliation: Division of Epidemiology and Public Health Medical School, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, United Kingdom.
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Muir
authors.affiliation: Division of Epidemiology and Public Health Medical School, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, United Kingdom.
authors.forename: Jo-Fen
authors.initials: JF
authors.lastname: Liu
authors.affiliation: Division of Epidemiology and Public Health Medical School, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, United Kingdom.
authors.forename: Richard F A
authors.initials: RFA
authors.lastname: Logan
authors.affiliation: Division of Epidemiology and Public Health Medical School, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, United Kingdom.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Grainge
authors.affiliation: Section of Cancer Genetics, Institute of Cancer Research, Sutton SM2 5NG, United Kingdom.
authors.forename: Richard S
authors.initials: RS
authors.lastname: Houlston
mesh_terms: D000236:Adenoma / Q000453:epidemiology / Q000235:genetics / Q000473:pathology*; D001241:Aspirin / Q000494:pharmacology* / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics / Q000473:pathology*; D051545:Cyclooxygenase 1 / Q000235:genetics*; D051546:Cyclooxygenase 2 / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors; D055502:Secondary Prevention
chemical_list: D016753:Interleukin-10; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D001241:Aspirin