556P - Integrin beta-3 genetic variants predict the risk of thrombo-embolic events in patients with colorectal cancer

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics Supportive Measures
Colon and Rectal Cancer
Translational Research
Basic Principles in the Management and Treatment (of cancer)
Presenter Gerald Prager
Citation Annals of Oncology (2014) 25 (suppl_4): iv167-iv209. 10.1093/annonc/mdu333
Authors G. Prager1, A. Schuler2, C. Pausz2, D. Bianconi2, H. Lenz3, C. Ay4, I. Pabinger4, C. Zielinski5
  • 1Department Of Medicine I, Vienna General Hospital (AKH) - Medizinische Universität Wien, 1090 - Vienna/AT
  • 2Department Of Medicine I, Medical University of Vienna, Vienna/AT
  • 3Norris Comprehensive Cancer Center, University of Southern California, Los Angeles/US
  • 4Department Of Medicine I, Medical University of Vienna, 1090 - Vienna/AT
  • 5Department Of Medicine I, Medical University of Viennas, 1090 - Vienna/AT

Abstract

Aim

Colorectal cancer patients are at increased risk for venous thromboembolism (VTE). Beta-3 integrin adhesion receptors play a central role in tumor cell biology, platelet aggregation and endothelial cell behavior. Therefore, we hypothesized that the germline single nucleotide polymorphisms (SNPs) rs3809865, which is thought to affect integrin expression, might predict the risk of VTE in colorectal cancer patients.

Methods

114/139 colorectal cancer patients were assessable for integrin beta-3 germline SNPs rs3809865 characterization within the study population recruited into the Vienna Cancer and Thrombosis Study (CATS) (Ay, C et al; JCO 2011 vol. 29 no. 15), an ongoing prospective observational cohort study initiated in October 2003 at the Medical University of Vienna. Whole blood samples were analyzed using PCR-RFLP or direct DNA-sequencing. VTE events were statistical analyzed using one-way Anova testing.

Results

The patient's demographics and tumor characteristics were balanced between groups. In 14 patients (12.28%) VTE occurred. 12 (25%) of 48 colorectal cancer patients with an rs3809865 A/A allele profile experienced a VTE, representing a statistical significant (p = 0.0015) increased risk of VTE when compared to other subgroups. Only 2 of 52 patients (3.85%) harboring an A/T allele VTE was of diagnosed and none (0%) of the T/T subgroup had any VTE. Other SNPs of the integrin beta-3 gene revealed no predictive value for VTE. In multivariable analysis including age, sex, chemotherapy, and anti-VEGF therapy rs3809865 A/A allele profile remained a statistical significant risk factor for VTE.

Conclusions

This study identifies the germline polymorphisms in integrin beta-3 gene rs3809865 as independent prognostic markers for VTE in colorectal cancer. These data may help to select subgroups of patients who may benefit from an enforced prophylaxis of venous thromboembolism (VTE).

Disclosure

All authors have declared no conflicts of interest.