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Original Articles
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
  • 4,629 View
  • 165 Download
  • 1 Crossref
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
Association of the inflammatory balance of diet and lifestyle with colorectal cancer among Korean adults: a case-control study
Shinyoung Jun, Jeonghee Lee, Jae Hwan Oh, Hee Jin Chang, Dae Kyung Sohn, Aesun Shin, Jeongseon Kim
Epidemiol Health. 2022;44:e2022084.   Published online September 30, 2022
DOI: https://doi.org/10.4178/epih.e2022084
  • 4,503 View
  • 187 Download
  • 3 Web of Science
  • 3 Crossref
AbstractAbstract AbstractSummary PDFSupplementary Material
Abstract
OBJECTIVES
Dietary and lifestyle exposures may affect the risk of colorectal cancer (CRC) by promoting chronic inflammation. Therefore, we assessed the separate and joint associations of dietary and lifestyle inflammation scores (DIS and LIS, respectively) with CRC.
METHODS
Data from 919 pathologically confirmed CRC cases and 1,846 age- and sex-matched controls recruited at the National Cancer Center Korea were analyzed. We calculated the DIS and LIS, which characterize the collective contributions of 19 dietary and 4 lifestyle factors, respectively, to systemic inflammation by applying weights based on high-sensitivity C-reactive protein. A higher score represented a higher balance of pro- to anti-inflammatory exposures. Unconditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for CRC risk compared across the DIS and LIS tertile categories, with the lowest tertile as the reference group.
RESULTS
The highest DIS tertile had significantly increased odds of having CRC (OR, 2.65; 95% CI, 2.10 to 3.36), and the odds increased with increasing DIS. The highest LIS tertile group had 1.28-fold higher odds of having CRC (95% CI, 1.03 to 1.58). In the cross-classification analysis, the odds of having CRC increased as the DIS and LIS jointly increased until the DIS reached the highest tertile, where the risk was very high (3-fold or more) regardless of the LIS.
CONCLUSIONS
In conclusion, a higher balance of pro-inflammatory relative to anti-inflammatory dietary and lifestyle factors, especially dietary factors, was associated with higher CRC risk among Korean adults.
Summary
Korean summary
본 연구는 국립암센터에서 수집한 대장암 환자-대조군 데이터를 활용하여, 새롭게 개발된 식이 염증 지수(Dietary Inflammation Score, DIS) 및 생활습관 염증 지수(Lifestyle Inflammation Score, LIS)와 대장암 발생 위험 간의 연관성을 탐색하였다. 분석 결과, 식이 염증 지수 혹은 생활습관 염증 지수가 높은 집단에서 대장암 위험이 더 높아, 식이와 생활습관이 체내 염증 수준을 높여 대장암 발생 위험을 높일 가능성이 제기되었다
Key Message
Dietary inflammation score (DIS) and lifestyle inflammation score (LIS) quantify the collective effect of dietary and lifestyle factors, respectively, on systemic inflammation. In this case-control study, we assessed the associations of DIS and LIS with colorectal cancer risk among Korean adults. Our results suggest that a higher balance of pro-to anti-inflammatory dietary and lifestyle factors may be associated with higher risk for colorectal cancer. The findings from our study support that reducing inflammation through dietary or lifestyle changes could potentially reduce the risk for colorectal cancer.

Citations

Citations to this article as recorded by  
  • The association of diet-dependent acid load with colorectal cancer risk: a case–control study in Korea
    Tao Thi Tran, Madhawa Gunathilake, Jeonghee Lee, Jae Hwan Oh, Hee Jin Chang, Dae Kyung Sohn, Aesun Shin, Jeongseon Kim
    British Journal of Nutrition.2024; 131(2): 333.     CrossRef
  • Gout and Colorectal Cancer Likelihood: Insights from a Nested Case-Control Study of the Korean Population Utilizing the Korean National Health Insurance Service-National Sample Cohort
    Mi Jung Kwon, Kyeong Min Han, Joo-Hee Kim, Ji Hee Kim, Min-Jeong Kim, Nan Young Kim, Hyo Geun Choi, Ho Suk Kang
    Cancers.2023; 15(23): 5602.     CrossRef
  • Dietary intake and cancer incidence in Korean adults: a systematic review and meta-analysis of observational studies
    Ji Hyun Kim, Shinyoung Jun, Jeongseon Kim
    Epidemiology and Health.2023; 45: e2023102.     CrossRef
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