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Sang-Hee Cho 1 Article
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
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AbstractAbstract AbstractSummary PDFSupplementary Material
Abstract
OBJECTIVES
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).
METHODS
From 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.
RESULTS
During 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.
CONCLUSIONS
Our findings do not support a causal role for genetically predisposed CRP levels in CRC survival.
Summary
Korean 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.

Citations

Citations to this article as recorded by  
  • 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

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