Cho Sooyoung, Song Nan, Choi Ji-Yeob, Shin Aesun
Department of Preventive Medicine, Seoul National University College of Medicine, Seoul 03080, Korea.
Cancer Research Institute, Seoul National University, Seoul 03080, Korea.
Cancers (Basel). 2020 Oct 12;12(10):2939. doi: 10.3390/cancers12102939.
Colorectal cancer is a common malignancy worldwide. Physical activity and a healthy diet contribute to energy balance and have been recommended for the prevention of colorectal cancer. We suggest that the individual differences in energy balance can be explained by genetic polymorphisms involved in mitochondria, which play a central role in energy metabolism at the cellular level. This study aimed to evaluate the association between genetic variants of the mitochondrial citric acid cycle and colorectal cancer. Study participants comprised 3523 colorectal cancer cases and 10,522 matched controls from the UK Biobank study. Odds ratios (ORs) and 95% confidence intervals (CIs) for colorectal cancer were estimated using a conditional logistic regression model. We found a significant association between the gene rs35494829 and colon cancer (ORs [95% CIs] per increment of the minor allele, 0.82 [0.74-0.92]). Statistical significance was observed in the interactions of the citric acid cycle variants with obesity, energy intake, and vigorous physical activity in colorectal cancer. We also identified significant SNP-SNP interactions among citric acid cycle SNPs in colorectal cancer. The results of this study may provide evidence for bioenergetics in the development of colorectal cancer and for establishing a precise prevention strategy.
结直肠癌是全球常见的恶性肿瘤。身体活动和健康饮食有助于能量平衡，已被推荐用于预防结直肠癌。我们认为能量平衡的个体差异可以由线粒体中涉及的基因多态性来解释，线粒体在细胞水平的能量代谢中起核心作用。本研究旨在评估线粒体柠檬酸循环基因变异与结直肠癌之间的关联。研究参与者包括来自英国生物银行研究的3523例结直肠癌病例和10522例匹配对照。使用条件逻辑回归模型估计结直肠癌的比值比（OR）和95%置信区间（CI）。我们发现基因rs35494829与结肠癌之间存在显著关联（每增加一个次要等位基因的OR[95%CI]，0.82[0.74-0.92]）。在结直肠癌中，观察到柠檬酸循环变异与肥胖、能量摄入和剧烈身体活动之间的相互作用具有统计学意义。我们还在结直肠癌的柠檬酸循环单核苷酸多态性（SNP）之间鉴定出显著的SNP-SNP相互作用。本研究结果可能为结直肠癌发生发展中的生物能量学以及制定精确的预防策略提供证据。
