title: Dopamine D2 receptor polymorphisms and adenoma recurrence in the Polyp Prevention Trial.
abstract: Epidemiological evidence suggests that obesity may be causally associated with colorectal cancer. Dopamine and the dopaminergic reward pathway have been implicated in drug and alcohol addiction as well as obesity. Polymorphisms within the D2 dopamine receptor gene (DRD2) have been shown to be associated with colorectal cancer risk. We investigated the association between DRD2 genotype at these loci and the risk of colorectal adenoma recurrence in the Polyp Prevention Trial. Odds ratios (OR) and 95% confidence intervals (CI) for risk of adenoma recurrence were calculated using unconditional logistic regression. Individuals with any, multiple (>or=2) or advanced adenoma recurrence after 4 years were compared to those without adenoma recurrence. Variation in intake of certain dietary components according to DRD2 genotype at 3 loci (rs1799732; rs6277; rs1800497) was also investigated. The DRD2 rs1799732 CT genotype was significantly associated with all adenoma recurrence (OR: 1.30; 95% CI: 1.01, 1.69). The rs1800497 TT genotype was also associated with a significantly increased risk of advanced adenoma recurrence (OR: 2.40; 95% CI: 1.11, 5.20). The rs1799732 CT and rs1800497 TT genotypes were significantly associated with adenoma recurrence in the Polyp Prevention Trial. Increased risk of adenoma recurrence as conferred by DRD2 genotypes may be related to difference in alcohol and fat intake across genotypes.
authors.affiliation: Cancer Prevention Fellowship Program, Office of Preventive Oncology, National Cancer Institute, Bethesda, MD 20892, USA. murphygw@mail.nih.gov
authors.forename: Gwen
authors.initials: G
authors.lastname: Murphy
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Cross
authors.forename: Leah S
authors.initials: LS
authors.lastname: Sansbury
authors.forename: Andrew
authors.initials: A
authors.lastname: Bergen
authors.forename: Adeyinka O
authors.initials: AO
authors.lastname: Laiyemo
authors.forename: Paul S
authors.initials: PS
authors.lastname: Albert
authors.forename: Zhuoqiao
authors.initials: Z
authors.lastname: Wang
authors.forename: Binbing
authors.initials: B
authors.lastname: Yu
authors.forename: Teresa
authors.initials: T
authors.lastname: Lehman
authors.forename: Aravind
authors.initials: A
authors.lastname: Kalidindi
authors.forename: Rama
authors.initials: R
authors.lastname: Modali
authors.forename: Arthur
authors.initials: A
authors.lastname: Schatzkin
authors.forename: Elaine
authors.initials: E
authors.lastname: Lanza
mesh_terms: D000236:Adenoma / Q000209:etiology / Q000235:genetics* / Q000517:prevention & control; D000328:Adult; D000368:Aged; D000428:Alcohol Drinking; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D004032:Diet; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000209:etiology / Q000235:genetics* / Q000517:prevention & control; D011110:Polymorphism, Genetic / Q000235:genetics*; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D012307:Risk Factors; D012907:Smoking
chemical_list: D017448:Receptors, Dopamine D2