The association of low-carbohydrate diet and HECTD4 rs11066280 polymorphism with the risk of colorectal cancer: a case-control study in Korea

Background Glucose is a main source of energy for tumor cells. Thus, low-carbohydrate diet (LCD) is thought to make a significant contribution to cancer prevention. Additionally, LCD and HECT domain E3 ubiquitin protein ligase 4 (HECTD4) gene may be related to insulin resistance. Objectives We explored whether LCD score and HECTD4 rs11066280 are etiological factors for CRC and whether LCD score interacts with HECTD4 rs11066280 to modify CRC risk. Methods We included 1,457 controls and 1,062 cases in a case-control study. LCD score was computed based on the proportion of energy obtained from carbohydrate, protein, and fat, as determined by a semi-quantitative food frequency questionnaire. We used unconditional logistic regression models to explore the association of HECTD4 with CRC prevention and interaction of LCD score and HECTD4 polymorphism with CRC preventability. Results Individuals with AA/AT genotypes who carried a minor allele (A) of HECTD4 rs11066280 exhibited a decreased CRC risk (odds ratio (OR)=0.75, 95% confidence interval (CI)= (0.62-0.91)). Additionally, a protective effect of high LCD score against CRC development was identified (OR=0.52, 95% CI=0.40-0.68, P for trend<0.001). However, the effect of LCD depended on individual’s genetic background, which appears only in participants with TT genotype of HECTD4 rs11066280 (OR=0.49 (0.36-0.68), P interaction=0.044). Conclusions Our findings suggest a protective effect of LCD and minor allele of HECTD4 rs11066280 against CRC development. Additionally, we provide an understanding of the interaction effect of LCD and HECTD4 rs11066280 on CRC, which may be helpful for establishing diet plans regarding cancer prevention.