Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2017

Interleukin-1 beta (IL1B) genetic variability is predictive of chemotherapy-induced gastrointestinal toxicity (CIGT) risk in patients receiving 5-fluorouracil. (#172)

Samantha K Korver 1 , Imogen A Ball 1 , Rachel J Gibson 1 2 , Jonathan Tuke 1 , Richard M Logan 1 , Alison Richards 3 , Kelly Mead 3 , Chris S Karapetis 3 , Dorothy M Keefe 4 , Joanne M Bowen 1 , Janet K Coller 1
  1. University of Adelaide, Adelaide, SA, Australia
  2. University of South Australia, Adelaide, SA, Australia
  3. Flinders Medical Centre, Adelaide, SA, Australia
  4. Royal Adelaide Hopsital, Adelaide, SA, Australia


Severe chemotherapy-induced gastrointestinal toxicity (CIGT) following 5-fluorouracil (5-FU) treatment is highly prevalent and negatively affects therapy. Currently, there are no diagnostic markers which predict a patient’s risk of severe CIGT prior to treatment. Our small pilot study investigated the relationship between genetic variants in the Toll-interleukin-1 Receptor (TIR) signalling pathway with the incidence of severe CIGT in 34 patients receiving 5-FU-based treatment. We reported an association between severe CIGT risk and TLR2 and TNF genetic variability and cancer type (receiver operator characteristic (ROC) area under the curve (AUC) of 87.3%). This study aimed to validate the results of the pilot study in a new, larger and independent cohort of participants.


Sixty-five participants (49 female) who completed 5-FU treatment at the Royal Adelaide Hospital and Flinders Medical Centre were recruited. CIGT data (severe toxicity: symptoms of Grade ≥3 NCI’s CTCAE v4, and early treatment cessation or reduction), demographics and treatment parameters were collected from clinical case review. Genetic variability in the following genes was determined using a customised Sequenom MassArray: IL1B, IL2, IL6, IL6R, IL10, TNF, TGFB, TLR2, TLR4, MD2, MYD88, BDNF, CRP and OPRM1. Multivariate logistic regression created a prediction model of severe CIGT risk and ROC curves assessed the model performance.


Thirteen (20%) participants experienced severe CIGT. Colorectal and gastric cancer as well as genetic variants in IL1B (rs16944 and rs1143634) were significantly associated with severe CIGT risk (P = 3.4x10-5), with a ROC AUC of 91.9%.


This study is ongoing. Although different genetic loci were identified as predictive in comparison to the pilot study, these results support that genetic variance in the TIR signalling pathway is predictive of severe CIGT risk. Further participants are being recruited to expand the study cohort to 150, giving 99% power at alpha =0.05 to detect toxicity risk.