Abstract
Purpose
Recent Mendelian randomization (MR) studies derived inconsistent results of blood lipids’ effect on colorectal cancer, and whether the blood lipids’ effect on colon and rectal cancer is different is still unknown. Here, we sought to answer these questions.
Methods
Primarily, we employed univariable MR to explore the blood lipids’ effect on colon and rectal cancer, including high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol and triglycerides. Then, multivariable MR was also employed to reassess each blood lipid’s effect on the two cancers with adjustment of the other lipids. Reverse MR analysis was adopted to determine whether colon or rectal cancer could affect the levels of blood lipids. The Cochrane’s Q value was used to evaluate the heterogeneity, and MR-PRESSO was used to appraise the pleiotropy.
Results
Generally, we did not find any significant result between blood lipids and the colon/rectal cancer after Bonferroni correction in the univariable MR analysis. The multivariable MR analysis also obtained the same results. However, it should be noted that higher total cholesterol level might increase the risk of colon cancer (OR = 1.15 [1.01, 1.31], IVW p value = 0.029) but not rectal cancer (OR = 1.02 [0.85, 1.21], IVW p value = 0.853). Such causal relationship turned insignificant in the multivariable MR. The reverse MR analysis suggested that either colon or rectal cancer could increase the levels of blood lipids.
Conclusion
We found no association between blood lipids and risk of colon or rectal cancer, except for a positive association between total cholesterol and colon cancer risk.
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Data availability
All GWAS summary statistics are publicly available.
Code availability
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XL proposed the idea, elaborated the research, and wrote the draft of the manuscript. Both XL and ZT contributed to the data analysis and manuscript revision. HC revised the manuscript. JD supervised the whole research and is responsible for the integrity of the study.
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Luo, X., Tu, Z., Chen, H. et al. Blood lipids and risk of colon or rectal cancer: a Mendelian randomization study. J Cancer Res Clin Oncol 147, 3591–3599 (2021). https://doi.org/10.1007/s00432-021-03790-5
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DOI: https://doi.org/10.1007/s00432-021-03790-5