Blood Lipids and the Risk of Colorectal Cancer: Mendelian Randomization Analyses in the Japanese Consortium of Genetic Epidemiology Studies-Reference-Cited by-同舟云学术

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

Published:2022-08-30 Issue:12 Volume:15 Page:827-836
ISSN:1940-6207
Container-title:Cancer Prevention Research
language:en
Short-container-title:

Author:

Iwagami Masao¹²^ORCID,Goto Atsushi¹³^ORCID,Katagiri Ryoko¹^ORCID,Sutoh Yoichi⁴^ORCID,Koyanagi Yuriko N.⁵^ORCID,Nakatochi Masahiro⁶^ORCID,Nakano Shiori¹^ORCID,Hanyuda Akiko¹⁷^ORCID,Narita Akira⁸^ORCID,Shimizu Atsushi⁴^ORCID,Tanno Kozo⁹^ORCID,Hozawa Atsushi¹⁰^ORCID,Kinoshita Kengo⁸^ORCID,Oze Isao¹¹^ORCID,Ito Hidemi⁵¹²^ORCID,Yamaji Taiki¹^ORCID,Sawada Norie¹³^ORCID,Nakamura Yohko¹⁴^ORCID,Nakamura Sho¹⁵¹⁶^ORCID,Kuriki Kiyonori¹⁷^ORCID,Suzuki Sadao¹⁸^ORCID,Hishida Asahi¹⁹^ORCID,Kasugai Yumiko²⁰^ORCID,Imoto Issei²¹^ORCID,Suzuki Midori²²^ORCID,Momozawa Yukihide²³^ORCID,Takeuchi Kenji¹⁹^ORCID,Yamamoto Masayuki²⁴^ORCID,Sasaki Makoto²⁵^ORCID,Matsuo Keitaro¹¹²⁶^ORCID,Tsugane Shoichiro¹³²⁷^ORCID,Wakai Kenji¹⁹^ORCID,Iwasaki Motoki¹¹³^ORCID

Affiliation:

1. 1Division of Epidemiology, National Cancer Center Institute for Cancer Control, Tokyo, Japan.

2. 2Department of Health Services Research, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.

3. 3Department of Health Data Science, Graduate School of Data Science, Yokohama City University, Kanagawa, Japan.

4. 4Division of Biomedical Information Analysis, Iwate Tohoku Medical Megabank, Iwate, Japan.

5. 5Division of Cancer Information and Control, Aichi Cancer Center, Aichi, Japan.

6. 6Public Health Informatics Unit, Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine, Aichi, Japan.

7. 7Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan.

8. 8Department of Integrative Genomics, Tohoku Medical Megabank Organization, Tohoku University, Miyagi, Japan.

9. 9Division of Clinical Research and Epidemiology, Iwate Tohoku Medical Megabank Organization, Iwate Medical University, Iwate, Japan.

10. 10Department of Preventive Medicine and Epidemiology, Tohoku Medical Megabank Organization, Tohoku University, Miyagi, Japan.

11. 11Division of Cancer Epidemiology and Prevention, Aichi Cancer Center, Aichi, Japan.

12. 12Division of Descriptive Cancer Epidemiology, Nagoya University Graduate School of Medicine, Aichi, Japan.

13. 13Division of Cohort Research, National Cancer Center Institute for Cancer Control, Tokyo, Japan.

14. 14Cancer Prevention Center, Chiba Cancer Center Research Institute, Chiba, Japan.

15. 15Graduate School of Health Innovation, Kanagawa University of Human Services, Kanagawa, Japan.

16. 16Cancer Prevention and Control Division, Kanagawa Cancer Center Research Institute, Kanagawa, Japan.

17. 17Laboratory of Public Health, School of Food and Nutritional Sciences, University of Shizuoka, Shizuoka, Japan.

18. 18Department of Public Health, Nagoya City University Graduate School of Medical Sciences, Aichi, Japan.

19. 19Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Aichi, Japan.

20. 20Division of Cancer Epidemiology and Prevention, Aichi Cancer Center, Aichi, Japan.

21. 21Aichi Cancer Center Research Institute, Aichi, Japan.

22. 22Core Facilities, Aichi Cancer Center Research Institute, Aichi, Japan.

23. 23Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan.

24. 24Tohoku Medical Megabank Organization, Tohoku University, Miyagi, Japan.

25. 25Iwate Tohoku Medical Megabank Organization, Iwate Medical University, Iwate, Japan.

26. 26Division of Cancer Epidemiology, Nagoya University Graduate School of Medicine, Aichi, Japan.

27. 27National Institute of Health and Nutrition, National Institutes of Biomedical Innovation, Health and Nutrition, Tokyo, Japan.

Abstract

Abstract 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.

Funder

National Cancer Center Japan

Ministry of Health, Labour and Welfare

Japan Agency for Medical Research and Development

Ministry of Education, Culture, Sports, Science and Technology

Publisher

American Association for Cancer Research (AACR)

Subject

Cancer Research,Oncology

Link

https://aacrjournals.org/cancerpreventionresearch/article-pdf/doi/10.1158/1940-6207.CAPR-22-0146/3204274/capr-22-0146.pdf

Reference44 articles.