Abstract 5216: The effect of polymorphisms in DAT1 and DRD4 on dietary intake during chemotherapy for childhood leukemia

Abstract

Abstract Outcomes of acute lymphoblastic leukemia (ALL) are associated with both host and environmental factors. We hypothesized that there is also an interaction between them, with genetic variants influencing dietary choices. The dopamine transporter 1 (DAT1) and D4 subtype of the dopamine receptor (DRD4) genes are polymorphic, with a variable number of nucleotide repeats (VNTR) that affect dopaminergic neurotransmission, and reward circuitry for food cravings. Specifically, the 9-tandem repeats (9R) allele of DAT1 and the 7-tandem repeats (7R) allele of DRD4 are risk factors for eating disorders or undereating behavior in children. The goal of this study was to determine whether these polymorphisms are associated with altered dietary intake during therapy for childhood ALL. DNA was isolated from peripheral blood mononuclear cells collected from 439 children being treated on Dana Farber Cancer Institute ALL Consortium Protocol 05-001 (NCT00400946). Target alleles in DAT1 and DRD4 were determined using PCR product length analysis. Each subject was classified as having either zero or at least one copy of the target alleles. Dietary intake was previously determined using food frequency questionnaires collected at three timepoints: time of diagnosis, end of induction, and continuation therapy. As previously published dietary composition in fat and carbohydrate differed significantly among three timepoints. There was no significant difference between those with or without the target alleles in DAT1 or DRD4 in percent from fat or percent from carbohydrate at any of the three timepoints. However, significant differences were observed when dietary intake was compared to the Dietary Reference Intake (DRI). Notably, a greater portion of male participants with DAT1 9R polymorphism had fat consumption below the DRI at the time of diagnosis. On the contrary, significantly decreased portion of females with DAT1 9R had fat consumption below the DRI during continuation therapy. When compared to normative values, a significantly increased number of children had total calorie consumption below DRI during induction therapy. The DRD4 7R polymorphism was associated with fat intake below DRI during induction therapy in males. However, neither DAT1 nor DRD4 polymorphisms were related to variation in carbohydrates consumption. In addition, a greater portion of participants that carry both DAT1 and DRD4 polymorphism exhibited a trend toward undereating behavior in fat intake compared to the controls. Our results are the first to indicate that DAT1 and DRD4 polymorphisms are associated with altered dietary intake during chemotherapy for childhood ALL. Future study will further elucidate whether this modulation is associated with changes in their body weight, BMI, glucose level, and disease relapse. Citation Format: Jing Wen, Arul Duggimpudi, Shengguo Li, Elena Ladas, Kara M. Kelly, Peter D. Cole. The effect of polymorphisms in DAT1 and DRD4 on dietary intake during chemotherapy for childhood leukemia. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5216.