Abstract 816: Genetic variants associated with C-reactive protein and colorectal cancer survival: Sex- and lifestyle factors- specific associations
Bibliographic record
Abstract
Abstract Background: Elevated levels of C-reactive protein (CRP) have been linked to colorectal cancer (CRC) survival and CRC prognostic factors, such as obesity, smoking, and alcohol consumption. However, the mechanisms underlying these associations are not well understood. We evaluated genetic variants associated with CRP levels and their interactions with sex and lifestyle factors in association with CRC-specific mortality. Methods: This study included 16,142 CRC cases from the International Survival Analysis in Colorectal Cancer Consortium (ISACC). We identified 741 common single nucleotide polymorphisms (SNPs) associated with CRP (minor allele frequency >5% in European ancestry) from the NHGRI-EBI GWAS Catalog. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for SNP-specific association with CRC-specific mortality adjusting for age, sex, genotyping platform/study, and the first three principal components of genetic ancestry. SNPs were examined using log-additive models. Likelihood ratio tests were used to investigate multiplicative gene-environment interactions between CRP-associated SNPs and sex, obesity, ever smoking, and alcohol consumption. We also conducted stratified analyses according to these factors. P values were adjusted using Bonferroni correction, with corrected P <0.05 considered statistically significant. Results: After a median of 4.7 years (interquartile range = 2.3 to 7.7 years) of follow-up since diagnosis, 5,472 (33.9%) deaths accrued, 3,547 (64.8%) of which were due to CRC. No variants were statistically significantly 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 mortality (corrected Pinteraction = 0.0004); women had higher CRC-specific mortality associated with the minor allele (HR = 1.11, 95% CI = 1.04 to 1.19) whereas an inverse association was observed for men (HR = 0.88, 95% CI = 0.82 to 0.94). There was no evidence of statistically significant interactions between CRP-associated SNPs and alcohol, obesity or smoking in association with CRC-specific mortality. Conclusions: Our study observed a statistically 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. Citation Format: Yuhan Huang, Xinwei Hua, Julia D. Labadie, Tabitha A. Harrison, James 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 White, Roger Milne, Graham Giles, Andrew T. Chan, Ulrike Peters, Polly A. Newcomb. Genetic variants associated with C-reactive protein and colorectal cancer survival: Sex- and lifestyle factors- specific associations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 816.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.005 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".