ArticleJournal of cancer research and clinical oncology2016
A novel genetic score model of UGT1A1 and TGFB pathway as predictor of severe irinotecan-related diarrhea in metastatic colorectal cancer patients.
Article in Journal of cancer research and clinical oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01282658 (Genetic Variants and the Efficacy or Severe Adverse Reactions of CPT-11 Based Regimens in mCRC), which is not on this map. Cited by 3 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Genetic Variants and the Efficacy or Severe Adverse Reactions of CPT-11 Based Regimens in mCRC
Who cites it
3 citing papers in PubMed, 6 citations in OpenAlex.
- A Systematic Review of Polygenic Models for Predicting Drug Outcomes.Journal of personalized medicine · 2022Review
- The Road so Far in Colorectal Cancer Pharmacogenomics: Are We Closer to Individualised Treatment?Journal of personalized medicine · 2020Review
- Predictive Value of UGT1A1*28 Polymorphism In Irinotecan-based Chemotherapy.Journal of Cancer · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeUGT1A1*28/*6 as predictors of severe irinotecan-related diarrhea (SIRD) were duplicated by many studies. However, some patients of lower risk genotype (UGT1A1*1/*1) still suffered SIRD and the extremely low frequency of UGT1A1*6/*6 limited its clinical usage. Previous studies proved that the transforming growth factor (TGFB) family may have some effect on MTX-induced mucositis. However, the associations between TGFB gene variants and SIRD have never been reported so far. Our aim was to improve the predictive value of UGT1A1 gene variants on SIRD.
methodsSix SNPs (TGFB1 rs1800469; TGFBR1 rs10733710, rs334354 and rs6478974; TGFBR2 rs3087465; UGT1A1*6) and UGT1A1*28 were selected for genotyping in 160 metastatic colorectal cancer patients treated with irinotecan in a prospective multicenter trial (NCT01282658).
resultsUGT1A1*6, UGT1A1*28, rs1800469 and rs3087465 were all associated with SIRD (p = 0.026, 0.014, 0.047 and 0.045 respectively). A novel genetic score model (with a cut off value of 1.5) based on them was created to predict SIRD (OR = 11.718; 95 % CI 2.489-55.157, p = 0.002). In patients of gene score > 1.5, the risk of SIRD was much higher (23.5 vs. 2.8 %, p = 2.24E-04) and continued in the first 6 cycles of chemotherapy, while in patients with gene score ≤1.5, the risk was much lower and none of them suffered SIRD after the first cycle of chemotherapy (p = 0.0003).
conclusionsThe novel genetic score model improved the predictive value of UGT1A1 on SIRD. If validated, it will provide valuable information for clinical use of irinotecan.
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