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- Causal effect of serum matrix metalloproteinase levels on venous thromboembolism: a Mendelian randomization study
- Deheng Han, Fangcong Yu, Liangrong Zheng
- Epidemiol Health. 2024;46:e2024046. Published online April 7, 2024
- DOI: https://doi.org/10.4178/epih.e2024046
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AbstractOBJECTIVES
Serum matrix metalloproteinase (MMP) levels are associated with cardiovascular diseases. However, the causal associations between serum levels of specific MMPs and venous thromboembolism (VTE) remain unclear. The present study sought to explore the causal relationship between serum MMP levels and VTE by using the Mendelian randomization (MR) method.METHODSIn this study 2-sample MR study, the exposure data on serum MMP levels were derived from genome-wide association studies involving 21,758 individuals from 13 cohorts of European descent. The outcome data on VTE, including deep vein thrombosis and pulmonary embolism, were derived from the FinnGen research project. The primary method used was the inverse-variance weighting method. The MR-Egger intercept test and the Cochran Q test were used to evaluate pleiotropy and heterogeneity.RESULTSUsing the inverse-variance weighting method, higher serum MMP-12 levels were found to be associated with an increased risk of VTE (odds ratio, 1.04; 95% confidence interval, 1.01 to 1.07; p=0.001). Moreover, there was a weak association between the levels of certain MMPs and VTE. Sensitivity analyses revealed no significant heterogeneity and pleiotropy in our study, and the Steiger directionality test did not reveal a significant reverse causation association.CONCLUSIONSThere is a causal association between MMP-12 levels and VTE, which may have substantial implications for the diagnostic and therapeutic strategies used for VTE. -
SummaryKey Message
We found that there is a causal association between matrix metalloproteinase-12 levels and venous thromboembolism. Serum matrix metalloproteinase may have profound implications on the diagnostic andtherapeutic strategies used for venous thromboembolism.- No association between genetically predicted C-reactive protein levels and colorectal cancer survival in Korean: two-sample Mendelian randomization analysis
- Chang Kyun Choi, Jung-Ho Yang, Min-Ho Shin, Sang-Hee Cho, Sun-Seog Kweon
- Epidemiol Health. 2023;45:e2023039. Published online March 22, 2023
- DOI: https://doi.org/10.4178/epih.e2023039
- 6,339 View
- 176 Download
- 1 Web of Science
- 1 Crossref
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Abstract
Summary
PDFSupplementary Material
-
AbstractOBJECTIVES
Elevated C-reactive protein (CRP) levels are associated with an increased risk for colorectal cancer (CRC), as well as a poor prognosis, but it remains unclear whether these associations are causal. This study examined the potential causality between CRP levels and CRC survival using 2-sample Mendelian randomization (MR).METHODSFrom the Korean Genome and Epidemiology Study, a genome-wide association study (n=59,605), 7 single-nucleotide polymorphisms (SNPs) related to log2-transformed CRP levels were extracted as instrumental variables for CRP levels. The associations between the genetically predicted CRP and CRC-specific and overall mortality among CRC patients (n=6,460) were evaluated by Aalen’s additive hazard model. The sensitivity analysis excluded a SNP related to the blood lipid profile.RESULTSDuring a median of 8.5 years of follow-up, among 6,460 CRC patients, 2,676 (41.4%) CRC patients died from all causes and 1,622 (25.1%) died from CRC. Genetically predicted CRP levels were not significantly associated with overall or CRC-specific mortality in CRC patients. The hazard difference per 1,000 person-years for overall and CRC-specific mortality per 2-fold increase in CRP levels was -2.92 (95% confidence interval [CI], -14.05 to 8.21) and -0.76 (95% CI, -9.61 to 8.08), respectively. These associations were consistent in a subgroup analysis according to metastasis and a sensitivity analysis excluding possible pleiotropic SNPs.CONCLUSIONSOur findings do not support a causal role for genetically predisposed CRP levels in CRC survival. -
SummaryKorean summary
이 연구는 two-sample Mendelian randomization (MR)을 이용하여 대장암에서 C-reactive protein와 사망률 간의 관련성을 평가하였다. Two-sample MR은 한국유전체역학조사사업 (the Korean Genome and Epidemiology Study, KoGES) 참가자 59,605명에서 혈청 C-reactive protein에 대한 전장유전체 분석을 시행하여 7개의 단일염기다형성을 선별하였고, 화순암역학연구-대장암 (thw Hwasun Cancer Epidemiology Study-Colon and Rectum Cancer, HCES-CRC)에 등록된 6,460명 대장암 환자에서 그 7개 단일염기다형성과 사망률 간의 관련성을 평가한 결과를 이용하였다. 그 결과, 높은 혈청 C-reactive protein을 가지는 유전적 성향은 대장암 환자에서 사망률과의 통계적으로 유의한 관련성을 찾을 수 없었다.Key Message
This study employed a two-sample Mendelian randomization (MR) analysis to investigate the relationship between serum C-reactive protein (CRP) levels and mortality in colorectal cancer. The analysis utilized genome-wide association analysis (GWAS) data from 59,605 participants in the Korean Genome and Epidemiology Study (KoGES) for serum CRP and 6,460 colorectal cancer cases from the Hwasun Cancer Epidemiology Study-Colon and Rectum Cancer for mortality. Our findings suggest that there is no statistically significant association between genetically predisposed serum CRP levels and mortality. Consequently, our study does not support a causal effect of CRP on mortality in colorectal cancer. -
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- Mortality risk among adult americans living with cancer and elevated CRP
Srikanta Banerjee, Jagdish Khubchandani, Shalika Tisinger, Kavita Batra, Maribeth Greenway
Cancer Epidemiology.2024; 90: 102569. CrossRef
- Mortality risk among adult americans living with cancer and elevated CRP
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