Iwagami Masao, Goto Atsushi, Katagiri Ryoko, Sutoh Yoichi, Koyanagi Yuriko N, Nakatochi Masahiro, Nakano Shiori, Hanyuda Akiko, Narita Akira, Shimizu Atsushi, Tanno Kozo, Hozawa Atsushi, Kinoshita Kengo, Oze Isao, Ito Hidemi, Yamaji Taiki, Sawada Norie, Nakamura Yohko, Nakamura Sho, Kuriki Kiyonori, Suzuki Sadao, Hishida Asahi, Kasugai Yumiko, Imoto Issei, Suzuki Midori, Momozawa Yukihide, Takeuchi Kenji, Yamamoto Masayuki, Sasaki Makoto, Matsuo Keitaro, Tsugane Shoichiro, Wakai Kenji, Iwasaki Motoki
Division of Epidemiology, National Cancer Center Institute for Cancer Control, Tokyo, Japan.
Department of Health Services Research, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
Cancer Prev Res (Phila). 2022 Dec 1;15(12):827-836. doi: 10.1158/1940-6207.CAPR-22-0146.
The associations between blood lipids, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglycerides, and low-density lipoprotein cholesterol (LDL-C), and colorectal cancer risk are controversial. We evaluated potential causal relationships between blood lipids and colorectal cancer risk. Using the baseline data from the Japanese Consortium of Genetic Epidemiology studies, we estimated the single-nucleotide polymorphism (SNP)-exposure associations (n = 34,546 for TC, n = 50,290 for HDL-C, n = 51,307 for triglycerides, and n = 30,305 for LDL-C). We also estimated the SNP-outcome associations in another Japanese dataset (n = 7,936 colorectal cancer cases and n = 38,042 controls). We conducted Mendelian randomization (MR) analyses for the association between each blood lipid type and the risk of colorectal cancer using an inverse variance-weighted method. The total variances explained by the selected SNPs in TC (68 SNPs), HDL-C (50 SNPs), log-transformed triglycerides (26 SNPs), and LDL-C (35 SNPs) were 7.0%, 10.0%, 6.2%, and 5.7%, respectively. The odds ratios for colorectal cancer were 1.15 [95% confidence interval (CI), 1.01-1.32] per 1 standard deviation (SD; 33.3 mg/dL) increase in TC, 1.11 (95% CI, 0.98-1.26) per 1 SD (15.4 mg/dL) increase in HDL-C, 1.06 (95% CI, 0.90-1.26) per 1 SD (0.5 log-mg/dL) increase in log-transformed triglycerides, and 1.17 (95% CI, 0.91-1.50) per 1 SD (29.6 mg/dL) increase in LDL-C. Sensitivity analyses consistently suggested the positive association between TC and colorectal cancer, whereas results of each lipid component were inconsistent. In conclusion, this large MR study of a Japanese population showed a potentially causal association between high TC and colorectal cancer risk, although the association between each lipid component and colorectal cancer remained inconclusive.
In this large MR analysis of a Japanese population, a positive association was found between genetically predicted high total cholesterol (TC) levels and an increased risk of colorectal cancer. Therefore, lowering TC levels by lifestyle modifications or medications may be justified for the purpose of preventing colorectal cancer.
包括总胆固醇（TC）、高密度脂蛋白胆固醇（HDL-C）、甘油三酯和低密度脂蛋白胆固醇（LDL-C）在内的血脂与结直肠癌风险之间的关联存在争议。我们评估了血脂与结直肠癌风险之间潜在的因果关系。利用日本遗传流行病学研究联盟的基线数据，我们估计了单核苷酸多态性（SNP）-暴露关联（TC为34546例，HDL-C为50290例，甘油三酯为51307例，LDL-C为30305例）。我们还在另一个日本数据集中估计了SNP-结果关联（7936例结直肠癌病例和38042例对照）。我们使用逆方差加权法对每种血脂类型与结直肠癌风险之间的关联进行孟德尔随机化（MR）分析。所选SNP在TC（68个SNP）、HDL-C（50个SNP）、对数转换后的甘油三酯（26个SNP）和LDL-C（35个SNP）中解释的总方差分别为7.0%、10.0%、6.2%和5.7%。每增加1个标准差（SD；33.3mg/dL）的TC，结直肠癌的比值比为1.15[95%置信区间（CI），1.01-1.32]；每增加1个SD（15.4mg/dL）的HDL-C，比值比为1.11（95%CI，0.98-1.26）；每增加1个SD（0.5对数mg/dL）的对数转换后的甘油三酯，比值比为1.06（95%CI，0.90-1.26）；每增加1个SD（29.6mg/dL）的LDL-C，比值比为1.17（95%CI，0.91-1.50）。敏感性分析一致表明TC与结直肠癌之间存在正相关，而每种脂质成分的结果不一致。总之，这项针对日本人群的大型MR研究表明，高TC与结直肠癌风险之间可能存在因果关联，尽管每种脂质成分与结直肠癌之间的关联仍无定论。
在这项针对日本人群的大型MR分析中，发现基因预测的高总胆固醇（TC）水平与结直肠癌风险增加之间存在正相关。因此，为预防结直肠癌，通过生活方式改变或药物降低TC水平可能是合理的。
