Blood Lipids and the Risk of Colorectal Cancer: Mendelian Randomization Analyses in the Japanese Consortium of Genetic Epidemiology Studies

Autor: Masao Iwagami, Atsushi Goto, Ryoko Katagiri, Yoichi Sutoh, Yuriko N. Koyanagi, Masahiro Nakatochi, Shiori Nakano, Akiko Hanyuda, Akira Narita, Atsushi Shimizu, Kozo Tanno, Atsushi Hozawa, Kengo Kinoshita, Isao Oze, Hidemi Ito, Taiki Yamaji, Norie Sawada, Yohko Nakamura, Sho Nakamura, Kiyonori Kuriki, Sadao Suzuki, Asahi Hishida, Yumiko Kasugai, Issei Imoto, Midori Suzuki, Yukihide Momozawa, Kenji Takeuchi, Masayuki Yamamoto, Makoto Sasaki, Keitaro Matsuo, Shoichiro Tsugane, Kenji Wakai, Motoki Iwasaki
Rok vydání: 2022
Předmět:
Zdroj: Cancer Prevention Research. 15:827-836
ISSN: 1940-6215
1940-6207
Popis: 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. Prevention Relevance: 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.
Databáze: OpenAIRE
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