No association between genetically predicted C-reactive protein levels and colorectal cancer survival in Korean: two-sample Mendelian randomization analysis

• 영문명: No association between genetically predicted C-reactive protein levels and colorectal cancer survival in Korean: two-sample Mendelian randomization analysis
• 발행기관: 한국역학회
• 저자명: Chang Kyun Choi Jung-Ho Yang Min-Ho Shin Sang-Hee Cho Sun-Seog Kweon
• 간행물 정보: 『Epidemiology and Health』45, 1~8쪽, 전체 8쪽
• 주제분류: 의약학 > 면역학
• 파일형태: PDF
• 발행일자: 2023.01.01

영문 초록

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.

목차

INTRODUCTION

MATERIALS AND METHODS

RESULTS

DISCUSSION

SUPPLEMENTARY MATERIALS

CONFLICT OF INTEREST

FUNDING

ACKNOWLEDGEMENTS

AUTHOR CONTRIBUTIONS

ORCID

REFERENCES

키워드

Colorectal neoplasm C-reactive protein Survival analysis Mendelian randomization analysis