The Causal Relationship between PCSK9 Inhibitors and Malignant Tumors: A Mendelian Randomization Study Based on Drug Targeting
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design
2.2. Selection of Instrumental Variables
2.3. Sources of Outcome Data
2.4. Reverse Mendelian Randomization Validation
2.5. Data Analysis
3. Result
3.1. Causal Relationship between PCSK9 Inhibitors and CHD
3.2. Causal Relationship between PCSK9 Inhibitors and Tumors
3.3. Sensitivity, Heterogeneity, and Horizontal Pleiotropy Analysis
3.4. Reverse Mendelian Randomization Validation
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Outcome | Method | nsnp | pval | or | or_lci95 | or_uci95 |
---|---|---|---|---|---|---|
CHD | IVW | 9 | 0.000105 | 0.412278 | 0.03543 | 0.859984 |
Breast cancer | IVW | 33 | 0.046465 | 0.915973 | 0.829577 | 1.002369 |
Gastric cancer | IVW | 33 | 0.009436 | 1.466226 | 1.177273 | 1.755179 |
Hepatic cancer | IVW | 33 | 0.031913 | 1.748559 | 1.238079 | 2.259039 |
Lung cancer | IVW | 29 | 0.001287 | 0.770876 | 0.612424 | 0.929328 |
Oral cavity and pharyngeal cancer | IVW | 26 | 4.74 × 10−5 | 12.95632 | 11.7222 | 14.19044 |
Carcinoma in situ of cervix uteri, endocervix | IVW | 29 | 0.006413 | 6.024705 | 4.733405 | 7.316005 |
Malignant neoplasm of brain | IVW | 29 | 0.13796 | 0.584619 | 0.12463 | 1.293866 |
Bladder cancer | IVW | 33 | 0.817092 | 1.000201 | 0.9985 | 1.001901 |
Thyroid cancer | IVW | 33 | 0.640864 | 1.11934 | 0.645657 | 1.593023 |
Malignant neoplasm of kidney, except renal pelvis | IVW | 29 | 0.806225 | 0.941211 | 0.457094 | 1.425327 |
Malignant neoplasm of esophagus | IVW | 29 | 0.613284 | 1.284654 | 0.31321 | 2.256097 |
Pancreatic cancer | IVW | 4 | 0.246173 | 0.343108 | −1.46481 | 2.151024 |
Colorectal cancer | IVW | 33 | 0.703725 | 1.039738 | 0.838898 | 1.240578 |
Outcome | Heterogeneity Test (Q-Value) | Pleiotropy Test (p-Value) | Outlier Test (p-Value) | |
---|---|---|---|---|
MR-Egger | IVW | |||
CHD | 0.89 | 0.81 | 0.25 | NA |
Breast cancer | 0.49 | 0.46 | 0.25 | NA |
Gastric cancer | 0.74 | 0.74 | 0.35 | NA |
Hepatic cancer | 0.73 | 0.75 | 0.45 | NA |
Lung cancer | 0.72 | 0.60 | 0.08 | NA |
Oral cavity and pharyngeal cancer | 0.75 | 0.61 | 0.70 | NA |
Carcinoma in situ of cervix uteri, endocervix | 0.87 | 0.79 | 0.18 | NA |
Malignant neoplasm of brain | 0.63 | 0.41 | 0.073 | NA |
Bladder cancer | 0.97 | 0.98 | 0.55 | NA |
Thyroid cancer | 0.97 | 0.98 | 0.82 | NA |
Malignant neoplasm of kidney, except renal pelvis | 0.85 | 0.87 | 0.56 | NA |
Malignant neoplasm of esophagus | 0.82 | 0.84 | 0.48 | NA |
Pancreatic cancer | 0.97 | 0.97 | 0.72 | NA |
Colorectal cancer | 0.25 | 0.17 | 0.13 | NA |
Outcome | Heterogeneity Test (Q-Value) | Pleiotropy Test (p-Value) | Outlier Test (p-Value) | |
---|---|---|---|---|
MR-Egger | IVW | |||
CHD | 0.76 | 0.87 | 0.90 | NA |
Breast cancer | 0.71 | 0.75 | 0.85 | NA |
Gastric cancer | 0.67 | 0.70 | 0.61 | NA |
Hepatic cancer | 0.60 | 0.65 | 0.92 | NA |
Lung cancer | 0.12 | 0.13 | 0.44 | NA |
Oral cavity and pharyngeal cancer | 0.60 | 0.63 | 0.48 | NA |
Carcinoma in situ of cervix uteri, endocervix | 0.90 | 0.86 | 0.14 | NA |
Malignant neoplasm of brain | 0.49 | 0.36 | 0.075 | NA |
Bladder cancer | 0.99 | 0.99 | 0.62 | NA |
Thyroid cancer | 0.98 | 0.99 | 0.79 | NA |
Malignant neoplasm of kidney, except renal pelvis | 0.42 | 0.45 | 0.52 | NA |
Malignant neoplasm of esophagus | 0.69 | 0.60 | 0.11 | NA |
Pancreatic cancer | 0.96 | 0.95 | 0.99 | NA |
Colorectal cancer | 0.19 | 0.21 | 0.51 | NA |
Exposure | Method | nsnp | pval | or | or_lci95 | or_uci95 |
---|---|---|---|---|---|---|
CHD | IVW | 41 | 0.373 | 1.029 | 0.966 | 1.095 |
Breast cancer | IVW | 240 | 0.978 | 0.998 | 0.987 | 1.013 |
Gastric cancer | IVW | 24 | 0.453 | 0.996 | 0.985 | 1.006 |
Hepatic cancer | IVW | 23 | 0.149 | 0.989 | 0.974 | 1.003 |
Lung cancer | IVW | 53 | 0.554 | 0.994 | 0.976 | 1.012 |
Oral cavity and pharyngeal cancer | IVW | 16 | 0.229 | 1.005 | 0.996 | 1.014 |
Carcinoma in situ of cervix uteri, endocervix | IVW | 6 | 0.773 | 1.000 | 0.996 | 1.004 |
Malignant neoplasm of brain | IVW | 10 | 0.983 | 0.999 | 0.995 | 1.003 |
Bladder cancer | IVW | 25 | 0.482 | 2.195 | 0.244 | 19.730 |
Thyroid cancer | IVW | 13 | 0.683 | 0.998 | 0.989 | 1.007 |
Malignant neoplasm of kidney, except renal pelvis | IVW | 15 | 0.488 | 1.002 | 0.994 | 1.010 |
Malignant neoplasm of esophagus | IVW | 8 | 0.221 | 0.997 | 0.993 | 1.001 |
Pancreatic cancer | IVW | 3 | 0.352 | 1.040 | 0.956 | 1.132 |
Colorectal cancer | IVW | 69 | 0.364 | 1.009 | 0.989 | 1.028 |
Exposure | Method | nsnp | pval | or | or_lci95 | or_uci95 |
---|---|---|---|---|---|---|
CHD | IVW | 41 | 0.113 | 1.053 | 0.987 | 1.124 |
Breast cancer | IVW | 240 | 0.728 | 1.002 | 0.990 | 1.013 |
Gastric cancer | IVW | 24 | 0.944 | 0.999 | 0.990 | 1.008 |
Hepatic cancer | IVW | 23 | 0.067 | 0.989 | 0.978 | 1.000 |
Lung cancer | IVW | 53 | 0.949 | 1.000 | 0.984 | 1.016 |
Oral cavity and pharyngeal cancer | IVW | 16 | 0.133 | 1.006 | 0.997 | 1.015 |
Carcinoma in situ of cervix uteri, endocervix | IVW | 6 | 0.603 | 1.000 | 0.997 | 1.004 |
Malignant neoplasm of brain | IVW | 10 | 0.606 | 0.999 | 0.996 | 1.002 |
Bladder cancer | IVW | 25 | 0.339 | 2.022 | 0.477 | 8.575 |
Thyroid cancer | IVW | 13 | 0.391 | 0.996 | 0.988 | 1.004 |
Malignant neoplasm of kidney, except renal pelvis | IVW | 15 | 0.408 | 1.002 | 0.996 | 1.008 |
Malignant neoplasm of esophagus | IVW | 8 | 0.362 | 0.997 | 0.993 | 1.002 |
Pancreatic cancer | IVW | 3 | 0.412 | 1.040 | 0.946 | 1.143 |
Colorectal cancer | IVW | 69 | 0.550 | 1.005 | 0.988 | 1.022 |
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Wang, W.; Li, W.; Zhang, D.; Mi, Y.; Zhang, J.; He, G. The Causal Relationship between PCSK9 Inhibitors and Malignant Tumors: A Mendelian Randomization Study Based on Drug Targeting. Genes 2024, 15, 132. https://doi.org/10.3390/genes15010132
Wang W, Li W, Zhang D, Mi Y, Zhang J, He G. The Causal Relationship between PCSK9 Inhibitors and Malignant Tumors: A Mendelian Randomization Study Based on Drug Targeting. Genes. 2024; 15(1):132. https://doi.org/10.3390/genes15010132
Chicago/Turabian StyleWang, Wenxin, Wei Li, Dan Zhang, Yongrun Mi, Jingyu Zhang, and Guoyang He. 2024. "The Causal Relationship between PCSK9 Inhibitors and Malignant Tumors: A Mendelian Randomization Study Based on Drug Targeting" Genes 15, no. 1: 132. https://doi.org/10.3390/genes15010132
APA StyleWang, W., Li, W., Zhang, D., Mi, Y., Zhang, J., & He, G. (2024). The Causal Relationship between PCSK9 Inhibitors and Malignant Tumors: A Mendelian Randomization Study Based on Drug Targeting. Genes, 15(1), 132. https://doi.org/10.3390/genes15010132