본문 바로가기
KERD
논문KCI 등재

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

1

조회

0

다운로드

0

인용

0

참고문헌

키워드

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.

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.

참고문헌 (50)

  1. Wu J, "Circulating C-reactive protein and colorectal cancer risk : a report from the Shanghai Men’s Health Study", Carcinogenesis, 34, pp.2799~2803 (2013)
  2. Zhou B, "C-reactive protein, interleukin-6 and the risk of colorectal cancer : a meta-analysis", Cancer Causes Control, 25, pp.1397~1405 (2014)
  3. Goyal A, "C-reactive protein and colorectal cancer mortality in U. S. adults", Cancer Epidemiol Biomarkers Prev, 23, pp.1609~1618 (2014)
  4. Swede H, "Baseline serum C-reactive protein and death from colorectal cancer in the NHANES III cohort", Int J Cancer, 134, pp.1862~1870 (2014)
  5. Partl R, "The elevated pre-treatment C-reactive protein predicts poor prognosis in patients with locally advanced rectal cancer treated with neo-adjuvant radiochemotherapy", Diagnostics(Basel), 10, pp.780~ (2020)
  6. Yamamoto M, "Prognostic value of the combination of pre-and postoperative C-reactive protein in colorectal cancer patients", Surg Today, 48, pp.986~993 (2018)
  7. Ishizuka M, "C-reactive protein is associated with distant metastasis of T3 colorectal cancer", Anticancer Res, 32, pp.1409~1415 (2012)
  8. Fujikawa H, "Cumulative C-reactive protein in the perioperative period as a novel marker for oncological outcome in patients with colorectal cancer undergoing curative resection", J Anus Rectum Colon, 5, pp.281~290 (2021)
  9. Stephensen BD, "C-reactive protein trajectory to predict colorectal anastomotic leak : PREDICT Study", Br J Surg, 107, pp.1832~1837 (2020)
  10. Shrotriya S, "C-reactive protein is an important biomarker for prognosis tumor recurrence and treatment response in adult solid tumors : a systematic review", PLoS One, 10, pp.e0143080~ (2015)
  11. Matsubara D, "The impact of postoperative inflammation on recurrence in patients with colorectal cancer", Int J Clin Oncol, 25, pp.602~613 (2020)
  12. Woo HD, "Association between preoperative C-reactive protein level and colorectal cancer survival : a meta-analysis", Cancer Causes Control, 26, pp.1661~1670 (2015)
  13. Liao CK, "Prognostic value of the C-reactive protein to albumin ratio in colorectal cancer : an updated systematic review and meta-analysis", World J Surg Oncol, 19, pp.139~ (2021)
  14. He L, "Prognostic value of the Glasgow Prognostic Score or modified Glasgow Prognostic Score for patients with colorectal cancer receiving various treatments : a systematic review and meta-analysis", Cell Physiol Biochem, 51, pp.1237~1249 (2018)
  15. Allin KH, "Elevated C-reactive protein in the diagnosis, prognosis, and cause of cancer", Crit Rev Clin Lab Sci, 48, pp.155~170 (2011)
  16. Hartwig FP, "Two-sample Mendelian randomization : avoiding the downsides of a powerful, widely applicable but potentially fallible technique", Int J Epidemiol, 45, pp.1717~1726 (2016)
  17. Ligthart S, "Genome analyses of >200, 000 individuals identify 58 loci for chronic inflammation and highlight pathways that link inflammation and complex disorders", Am J Hum Genet, 103, pp.691~706 (2018)
  18. Kocarnik JM, "Multiancestral analysis of inflammation-related genetic variants and C-reactive protein in the population architecture using genomics and epidemiology study", Circ Cardiovasc Genet, 7, pp.178~188 (2014)
  19. Vinayagamoorthy N, "New variants including ARG1 polymorphisms associated with C-reactive protein levels identified by genome-wide association and pathway analysis", PLoS One, 9, pp.e95866~ (2014)
  20. Huang Y, "Genetic variants associated with circulating C-reactive protein levels and colorectal cancer survival : sex-specific and lifestyle factors specific associations", Int J Cancer, 150, pp.1447~1454 (2022)
  21. Slattery ML, "Genetic variation in C-reactive protein in relation to colon and rectal cancer risk and survival", Int J Cancer, 128, pp.2726~2734 (2011)
  22. Yang SH, "Association of C-reactive protein gene polymorphisms and colorectal cancer", Ann Surg Oncol, 18, pp.1907~1915 (2011)
  23. Huang CJ, "Prognostic significance of C-reactive protein polymorphism and KRAS", BRAF in synchronous liver metastasis from colorectal cancer, 2013, pp.8, e65117~
  24. Hua X, "Genetically predicted circulating C-reactive protein concentration and colorectal cancer survival : a Mendelian randomization consortium study", Cancer Epidemiol Biomarkers Prev, 30, pp.1349~1358 (2021)
  25. Morimoto Y, "Ethnic differences in serum adipokine and C-reactive protein levels: the multiethnic cohort", Int J Obes(Lond), 38, pp.1416~1422 (2014)
  26. Okada Y, "Genome-wide association study for C-reactive protein levels identified pleiotropic associations in the IL6 locus", Hum Mol Genet, 20, pp.1224~1231 (2011)
  27. Kanai M, "Genetic analysis of quantitative traits in the Japanese population links cell types to complex human diseases", Nat Genet, 50, pp.390~400 (2018)
  28. Kim Y, "Cohort profile : the Korean Genome and Epidemiology Study(KoGES)consortium", Int J Epidemiol, 46, pp.e20~ (2017)
  29. Moon S, "The Korea Biobank Array : design and identification of coding variants associated with blood biochemical traits", Sci Rep, 9, pp.1382~ (2019)
  30. Choi CK, "Association between ALDH2 polymorphism and esophageal cancer risk in South Koreans : a case-control study", BMC Cancer, 21, pp.254~ (2021)
  31. Han MR, "Genome-wide association study in East Asians identifies two novel breast cancer susceptibility loci", Hum Mol Genet, 25, pp.3361~3371 (2016)
  32. 최창균, "Association between ALDH2 Polymorphism and Gastric Cancer Risk in a Korean Population", Journal of Korean Medical Science, 35(17), pp.1~6 (2020), 대한의학회[DOI]
  33. Lu Y, "Large-scale genome-wide association study of East Asians identifies loci associated with risk for colorectal cancer", Gastroenterology, 156, pp.1455~1466 (2019)
  34. 최창균, "Association between ALDH2 and ADH1B Polymorphisms and the Risk for Colorectal Cancer in Koreans", Cancer Research and Treatment, 53(3), pp.754~762 (2021), 대한암학회[DOI]
  35. Cho Y, "Mendelian randomization analysis with survival outcomes", Genet Epidemiol, 45, pp.16~23 (2021)
  36. Yavorska OO, "MendelianRandomization : an R package for performing Mendelian randomization analyses using summarized data", Int J Epidemiol, 46, pp.1734~1739 (2017)
  37. Brion MJ, "Calculating statistical power in Mendelian randomization studies", Int J Epidemiol, 42, pp.1497~1501 (2013)
  38. Staley JR, "PhenoScanner : a database of human genotype-phenotype associations", Bioinformatics, 32, pp.3207~3209 (2016)
  39. Ligthart S, "Bivariate genome-wide association study identifies novel pleiotropic loci for lipids and inflammation", BMC Genomics, 17, pp.443~ (2016)
  40. Surakka I, "The impact of low-frequency and rare variants on lipid levels", Nat Genet, 47, pp.589~597 (2015)
  41. Bowden J, "Consistent estimation in Mendelian randomization with some invalid instruments using a weighted median estimator", Genet Epidemiol, 40, pp.304~314 (2016)
  42. Bowden J, "Mendelian randomization with invalid instruments : effect estimation and bias detection through Egger regression", Int J Epidemiol, 44, pp.512~525 (2015)
  43. Prins BP, "Genome-wide analysis of health-related biomarkers in the UK Household Longitudinal Study reveals novel associations", Sci Rep, 7, pp.11008~ (2017)
  44. Naitza S, "A genome-wide association scan on the levels of markers of inflammation in Sardinians reveals associations that underpin its complex regulation", PLoS Genet, 8, pp.e1002480~ (2012)
  45. Han KH, "C-reactive protein promotes monocyte chemoattractant protein-1--mediated chemotaxis through upregulating CC chemokine receptor 2 expression in human monocytes", Circulation, 109, pp.2566~2571 (2004)
  46. Theodoratou E, "Genome-wide scan of the effect of common nsSNPs on colorectal cancer survival outcome", Br J Cancer, 119, pp.988~993 (2018)
  47. Phipps AI, "Common genetic variation and survival after colorectal cancer diagnosis : a genome-wide analysis", Carcinogenesis, 37, pp.87~95 (2016)
  48. Ghuman S, "Serum inflammatory markers and colorectal cancer risk and survival", Br J Cancer, 116, pp.1358~1365 (2017)
  49. Allin KH, "Baseline C-reactive protein is associated with incident cancer and survival in patients with cancer", J Clin Oncol, 27, pp.2217~2224 (2009)
  50. Zhao H, "Inflammation and tumor progression : signaling pathways and targeted intervention", Signal Transduct Target Ther, 6, pp.263~ (2021)

관련 논문AI추천

이 간행물의 다른 논문 (102건)

Changes in health behaviors and obesity of Korean adolescents before and during the COVID-19 pandemic: a special report using the Korea Youth Risk Behavior SurveyChoi Sunhye, Oh Kyungwon, 오창모, Kim Yangha, Yang Ji Eunpp. 1-8Korea Seroprevalence Study of Monitoring of SARS-COV-2 Antibody Retention and Transmission (K-SEROSMART): findings from national representative sample황태윤, 오경재, 홍영습, Kim Su Young, 이계오, 윤규현, 김정애, 이혁민, 신민호, 이순영, 이원영, 김동현, 박재현, 이훈재, 조성일, 남해성, 이무식, Lee June-Woo, Kim Sung Soon, 설로마, Kim Byoungguk, 이중정, 오창모, Jung Sun Jae, 오성수, Yim Hyeon Woo, 한미아, 김유미, 조희숙, Lee Ju-Hyung, Jung Jaehun, Kim Ah-Ra, Han Jina, Baek Hye Jin, Noh Eunbi, Ryu Sukhyun, 박노례, Jung Eunok, Kim Sang Il, Hwang Yoo-Sung, Oh Sangcheol, Kim Migyeong, Yu Byengchul, Kim Keonyeop, Hwangbo Young, Lee Joongyub, Kim Hyeongsu, Kang Gilwon, Ryu So Yeon, Park Soon-Woo, Kim Sang Kyu, Park Ki Soo, Kwon Jun-wook, Jang Eun Young, Nam Jeonghyunpp. 1-13Genetically determined alcohol consumption and cancer risk in Korea지선하, 정금지, 백지우, Shin Sang Yoppp. 1-7Self-reported adverse events after 2 doses of COVID-19 vaccine in Korea고미정, 김형준, 황인섭, Kwon Yunhyung, Kim Seontae, Seo Soon-Young, Cho Enhi, Yeon-Kyeng Leepp. 1-7Detecting mpox infection in the early epidemic: an epidemiologic investigation of the third and fourth cases in KoreaChoi Jihyun, Choi Yunsang, Kim Jong Mu, 박숙경, Kim Taeyoung, Park Eonjoo, Eun Juk Suk, Lee Eun-young, Mun Ji Won, Lee Sinyoung, Yeom Hansol, Kim Eun Kyoung, Ha Jinhopp. 1-7