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, Oct 04, 2015
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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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    ABSTRACT: Background With over 1.3 billion people, India is estimated to contain three times more genetic diversity than does Europe. Next-generation sequencing technologies have facilitated the understanding of diversity by enabling whole genome sequencing at greater speed and lower cost. While genomes from people of European and Asian descent have been sequenced, only recently has a single male genome from the Indian subcontinent been published at sufficient depth and coverage. In this study we have sequenced and analyzed the genome of a South Asian Indian female (SAIF) from the Indian state of Kerala. Results We identified over 3.4 million SNPs in this genome including over 89,873 private variations. Comparison of the SAIF genome with several published personal genomes revealed that this individual shared ~50% of the SNPs with each of these genomes. Analysis of the SAIF mitochondrial genome showed that it was closely related to the U1 haplogroup which has been previously observed in Kerala. We assessed the SAIF genome for SNPs with health and disease consequences and found that the individual was at a higher risk for multiple sclerosis and a few other diseases. In analyzing SNPs that modulate drug response, we found a variation that predicts a favorable response to metformin, a drug used to treat diabetes. SNPs predictive of adverse reaction to warfarin indicated that the SAIF individual is not at risk for bleeding if treated with typical doses of warfarin. In addition, we report the presence of several additional SNPs of medical relevance. Conclusions This is the first study to report the complete whole genome sequence of a female from the state of Kerala in India. The availability of this complete genome and variants will further aid studies aimed at understanding genetic diversity, identifying clinically relevant changes and assessing disease burden in the Indian population.
    BMC Genomics 08/2012; 13(1):440. DOI:10.1186/1471-2164-13-440 · 3.99 Impact Factor
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    ABSTRACT: The dopamine D2 receptor (DRD2) has been implicated in modulating the rewarding effects of foods high in sugar. The purpose of this study was to determine whether a variation in the DRD2 gene affects habitual consumption of sugars in a free-living population. Caucasian men (n = 96) and women (n = 217) 20-29 years of age completed a 1-month food frequency questionnaire and were genotyped for the C957T polymorphism in the DRD2 gene. Analyses of covariance with post-hoc Tukey tests were used to compare nutrient intakes between genotypes adjusting for potential confounders. Among men, consumption of sucrose was 60 +/- 6, 48 +/- 4, and 39 +/- 5 g/day for those with the CC, CT and TT genotypes, respectively, with a significant difference between the homozygotes (p = 0.03), suggesting an additive mode of inheritance. Among women, sucrose consumption was 42 +/- 4, 53 +/- 2, and 44 +/- 4 g/day for the CC, CT and TT genotypes, respectively, with CC and CT differing significantly (p = 0.02), suggesting a partial heterosis mode of inheritance. No differences were observed for protein or fat. These findings suggest that genetic variation in DRD2 influences food selection and may explain some of the interindividual differences in sugar consumption.
    Journal of Nutrigenetics and Nutrigenomics 03/2010; 2(4-5):235-42. DOI:10.1159/000276991 · 2.00 Impact Factor
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