Tran Tao Thi, Gunathilake Madhawa, Lee Jeonghee, Oh Jae Hwan, Chang Hee Jin, Sohn Dae Kyung, Shin Aesun, Kim Jeongseon
Department of Cancer AI & Digital Health, Graduate School of Cancer Science and Policy, Goyang-si, Gyeonggi-do, South Korea.
Faculty of Public Health, University of Medicine and Pharmacy, Hue University, Hue City, Vietnam.
Curr Dev Nutr. 2024 Feb 27;8(3):102127. doi: 10.1016/j.cdnut.2024.102127. eCollection 2024 Mar.
Glucose is a main source of energy for tumor cells. Thus, a low-carbohydrate diet (LCD) is thought to make a significant contribution to cancer prevention. In addition, LCD and HECT domain E3 ubiquitin protein ligase 4 (HECTD4) gene may be related to insulin resistance.
We explored whether LCD score and HECTD4 rs11066280 are etiological factors for colorectal cancer (CRC) and whether LCD score interacts with HECTD4 rs11066280 to modify CRC risk.
We included 1457 controls and 1062 cases in a case-control study. The LCD score was computed based on the proportion of energy obtained from carbohydrate, protein, and fat, as determined by a semiquantitative 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.
Individuals with AA/AT genotypes who carried a minor allele (A) of rs11066280 exhibited a decreased CRC risk [odds ratio (OR) = 0.75, 95% confidence interval (CI): 0.62, 0.91]. In addition, a protective effect of high LCD score against CRC development was identified (OR = 0.52, 95% CI: 0.40, 0.68, for trend <0.001). However, the effect of LCD depended on individual's genetic background, which appears only in participants with TT genotype of rs11066280 [OR = 0.49 (0.36-0.68), interaction = 0.044].
Our findings suggest a protective effect of LCD and a minor allele of rs11066280 against CRC development. In addition, we provide an understanding of the interaction effect of LCD and rs11066280 on CRC, which may be helpful for establishing diet plans regarding cancer prevention.
葡萄糖是肿瘤细胞的主要能量来源。因此，低碳水化合物饮食（LCD）被认为对癌症预防有重要作用。此外，LCD与HECT结构域E3泛素蛋白连接酶4（HECTD4）基因可能与胰岛素抵抗有关。
我们探讨了LCD评分和HECTD4 rs11066280是否为结直肠癌（CRC）的病因，以及LCD评分是否与HECTD4 rs11066280相互作用以改变CRC风险。
在一项病例对照研究中，我们纳入了1457名对照者和1062例患者。LCD评分是根据通过半定量食物频率问卷确定的碳水化合物、蛋白质和脂肪所提供能量的比例计算得出的。我们使用无条件逻辑回归模型来探讨HECTD4与CRC预防的关联，以及LCD评分和HECTD4多态性与CRC可预防性的相互作用。
携带rs11066280次要等位基因（A）的AA/AT基因型个体的CRC风险降低[比值比（OR）=0.75，95%置信区间（CI）：0.62，0.91]。此外，还发现高LCD评分对CRC发生有保护作用（OR = 0.52，95% CI：0.40，0.68，趋势<0.001）。然而，LCD的作用取决于个体的遗传背景，仅在rs11066280 TT基因型的参与者中出现[OR = 0.49（0.36 - 0.68），相互作用=0.044]。
我们的研究结果表明LCD和rs11066280的次要等位基因对CRC发生有保护作用。此外，我们对LCD和rs11066280对CRC的相互作用效应有了认识，这可能有助于制定癌症预防的饮食计划。
