Dopamine D 2 receptor polymorphisms and adenoma recurrence in the Polyp Prevention Trial

Cancer Prevention Fellowship Program, Office of Preventive Oncology, National Cancer Institute, Bethesda, MD 20892, USA.
International Journal of Cancer (Impact Factor: 5.09). 05/2009; 124(9):2148-51. DOI: 10.1002/ijc.24079
Source: PubMed


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.

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Available from: Teresa A Lehman
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    • "Further, a SNP in CENPF gene (R2943G; rs438034) that occurs in the SAIF genome is associated with a poor breast cancer survival [50]. Other SNPs with increased cancer susceptibility include FCGR2A H166R (rs1801274) associated with increased risk for non-Hodgkin’s lymphoma [51], ANKK1 E713K (rs1800497; [52]) involved in advanced adenoma recurrence, HNF1A S487N (rs2464196; [53]), MMP9 Q166R (rs17576-rs2250889; [54]), and XPC Q939K (rs2228001; [55]) variants associated with lung cancer, ATG16L1 T137A (rs2241880; [56,57]) with Crohn’s disease, and OGG1 P332A (rs1052133; [58-60]) associated with bladder and gall-bladder cancer in Japanese, Chinese and Indian populations. An ATR (M211T; rs2227928) variant found in the genome has been associated with a poorer response to gemcitabine and radiation therapy in pancreatic cancer [61]. "
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