Genetic variants associated with circulating C-reactive protein levels and colorectal cancer survival: Sex-specific and lifestyle factors specific associations

Yuhan Huang, Xinwei Hua, Julia D. Labadie, Tabitha A. Harrison, James Y. Dai, Sara Lindstrom, Yi Lin, Sonja I. Berndt, Daniel D. Buchanan, Peter T. Campbell, Graham Casey, Steven J. Gallinger, Marc J. Gunter, Michael Hoffmeister, Mark A. Jenkins, Lori C. Sakoda, Robert E. Schoen, Brenda Diergaarde, Martha L. Slattery, Emily WhiteGraham Giles, Hermann Brenner, Jenny Chang-Claude, Amit Joshi, Wenjie Ma, Rish K. Pai, Andrew T. Chan, Ulrike Peters, Polly A. Newcomb

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Elevated blood levels of C-reactive protein (CRP) have been linked to colorectal cancer (CRC) survival. We evaluated genetic variants associated with CRP levels and their interactions with sex and lifestyle factors in association with CRC-specific mortality. Our study included 16 142 CRC cases from the International Survival Analysis in Colorectal Cancer Consortium. We identified 618 common single nucleotide polymorphisms (SNPs) associated with CRP levels from the NHGRI-EBI GWAS Catalog. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between SNPs and CRC-specific mortality adjusting for age, sex, genotyping platform/study and principal components. We investigated their interactions with sex and lifestyle factors using likelihood ratio tests. Of 5472 (33.9%) deaths accrued over up to 10 years of follow-up, 3547 (64.8%) were due to CRC. No variants were associated with CRC-specific mortality after multiple comparison correction. We observed strong evidence of interaction between variant rs1933736 at FRK gene and sex in relation to CRC-specific mortality (corrected Pinteraction =.0004); women had higher CRC-specific mortality associated with the minor allele (HR = 1.11, 95% CI = 1.04-1.19) whereas an inverse association was observed for men (HR = 0.88, 95% CI = 0.82-0.94). There was no evidence of interactions between CRP-associated SNPs and alcohol, obesity or smoking. Our study observed a significant interaction between sex and a CRP-associated variant in relation to CRC-specific mortality. Future replication of this association and functional annotation of the variant are needed.

Original languageEnglish (US)
Pages (from-to)1447-1454
Number of pages8
JournalInternational Journal of Cancer
Volume150
Issue number9
DOIs
StatePublished - May 1 2022
Externally publishedYes

Keywords

  • C-reactive protein
  • colorectal cancer
  • genetic variants
  • survival

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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