ArticleJournal of the National Cancer Institute2019
Pattern Recognition Receptor Polymorphisms as Predictors of Oxaliplatin Benefit in Colorectal Cancer.
Article in Journal of the National Cancer Institute, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.
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Who cites it
9 citing papers in PubMed, 1 synthesis or guideline pooled it, 11 citations in OpenAlex.
- Contribution of TLR4 to colorectal tumor microenvironment, etiology and prognosis.Journal of cancer research and clinical oncology · 2023Pooled it
- Pharmacogenetics Role of Genetic Variants in Immune-Related Factors: A Systematic Review Focusing on mCRC.Pharmaceutics · 2022Review
- Identification of a Novel Risk Model: A Five-Gene Prognostic Signature for Pancreatic Cancer.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- A loss-of-function polymorphism inOncoimmunology · 2022Article
- Polymorphism of formyl peptide receptor 1 (FPR1) reduces the therapeutic efficiency and antitumor immunity after neoadjuvant chemoradiotherapy (CCRT) treatment in locally advanced rectal cancer.Cancer immunology, immunotherapy : CII · 2021Article
- TRIM29 Reverses Oxaliplatin Resistance of P53 Mutant Colon Cancer Cell.Canadian journal of gastroenterology & hepatology · 2021Article
- Immunogenic cell death pathway polymorphisms for predicting oxaliplatin efficacy in metastatic colorectal cancer.Journal for immunotherapy of cancer · 2020Article
- What Should We Do Better? Lessons from Negative Results of a Biomarker Validation Study.Journal of the National Cancer Institute · 2019Article
- Impact of Pattern Recognition Receptors on the Prognosis of Chemotherapy-treated Rectal Cancer Patients.In vivo (Athens, Greece)Article
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Abstract
backgroundConstitutional loss of function (LOF) single nucleotide polymorphisms (SNPs) in pattern recognition receptors FPR1, TLR3, and TLR4 have previously been reported to predict oxaliplatin benefit in colorectal cancer. Confirmation of this association could substantially improve patient stratification.
methodsWe performed a retrospective biomarker analysis of the Short Course in Oncology Therapy (SCOT) and COIN/COIN-B trials. Participant status for LOF variants in FPR1 (rs867228), TLR3 (rs3775291), and TLR4 (rs4986790/rs4986791) was determined by genotyping array or genotype imputation. Associations between LOF variants and disease-free survival (DFS) and overall survival (OS) were analyzed by Cox regression, adjusted for confounders, using additive, dominant, and recessive genetic models. All statistical tests were two-sided.
resultsOur validation study populations included 2929 and 1948 patients in the SCOT and COIN/COIN-B cohorts, respectively, of whom 2728 and 1672 patients had functional status of all three SNPs determined. We found no evidence of an association between any SNP and DFS in the SCOT cohort, or with OS in either cohort, irrespective of the type of model used. This included models for which an association was previously reported for rs867228 (recessive model, multivariable-adjusted hazard ratio [HR] for DFS in SCOT = 1.19, 95% confidence interval [CI] = 0.99 to 1.45, P = .07; HR for OS in COIN/COIN-B = 0.92, 95% CI = 0.63 to 1.34, P = .66), and rs4986790 (dominant model, multivariable-adjusted HR for DFS in SCOT = 0.86, 95% CI = 0.65 to 1.13, P = .27; HR for OS in COIN/COIN-B = 1.08, 95% CI = 0.90 to 1.31, P = .40).
conclusionIn this prespecified analysis of two large clinical trials, we found no evidence that constitutional LOF SNPs in FPR1, TLR3, or TLR4 are associated with differential benefit from oxaliplatin. Our results suggest these SNPs are unlikely to be clinically useful biomarkers.
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