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Poster Display session

453 - Lymphotoxin alpha functional germline genetic variant: A future prognostic factor in colorectal cancer?

Date

14 Dec 2018

Session

Poster Display session

Presenters

Mariana Rocha

Citation

Annals of Oncology (2018) 29 (suppl_10): x1-x10. 10.1093/annonc/mdy493

Authors

M.S. Rocha1, F. Pinheiro2, B. Cardoso2, M. Del Rio1, A. Lojo Teira3, M. Pires4, E. Bastos2, R. Ribeiro5

Author affiliations

  • 1 Medical Oncology, Hospital Vila Real (CHTMAD), 5000-008 - Vila Real/PT
  • 2 Department Of Genetics And Biotechnology, School of Life and Environmental Sciences (ECVA), University of Trás-os-Montes e Alto Douro (UTAD), Vila Real/PT
  • 3 Medical Oncology, Hospital Vila Real (CHTMAD), 5000-000 - Vila Real/PT
  • 4 Animal And Veterinary Research Centre (cecav), University of Trás-os-Montes & Alto Douro (UTAD), Vila Real/PT
  • 5 Tumor & Microenvironment Interactions Group, i3S/INEB Institute for Research and Innovation in Health/Institute of Biomedical Engineering, University of Porto, Porto/PT
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Resources

Abstract 453

Background

Lymphotoxin alpha (LTa) is a pro-inflammatory cytokine expressed by inflammatory cells with a role in the regulation of tumor microenvironment (TM). A putatively functional genetic polymorphism in LTA, at locus +80 (Thr26Asn, rs1041981), has been associated with altered expression of LTa. Here, we sought to evaluate whether this polymorphism associates with 2 main endpoints (progression-free survival (PFS) and overall survival(OS)) in colorectal cancer (CRC).

Methods

This retrospective cohort study was conducted in 166 CRC patients from a single tertiary hospital. Whole blood was used to isolate genomic DNA. Genotyping of LTA +80 C > A was performed through real time-PCR allelic discrimination using specific Taqman probes, and confirmed by sequencing. Retrospective data and long-term outcomes were reviewed. Age and gender-adjusted logistic regression analyses were undertaken. Analyses were conducted after stratification by baseline lymphocyte count (LC) (LC < 1x103/µL vs > 1x103/µL). Kaplan-Meier curves with Log-Rank test were used. Subsequent multivariate Cox regression proportional hazards models were calculated (P for retention > 0.1).

Results

Participants’ median age was 65.9 (IR, 57.5-74.3) years, the majority were males (63%), and 58% with colon cancer. At diagnosis, 45,2% were stage III and 18,1% stage IV. The median follow up time was approximately 4 years (IQR, 25.5-67.0 months). We found a significant association in carriers of the A-allele to have lower LC on linear trend analysis (P for trend = 0.013). Multivariate comparisons between LTA genotypes of additive model showed an independent protective effect for heterozygous compared with C-homozygous in the association with disease progression (HR = 0.5, 95CI = 0.3-0.97, P = 0.041), only in subjects with baseline LC > 1x103/µL. In this group, a significant independent protective effect for all-cause mortality was observed in A-carriers (HR = 0.4, 95CI = 0.1-0.97, P = 0.042).

Conclusions

This LTA genetic variant in subjects with baseline LC > 1x103/µL is associated with PFS and OS in CRC. The understanding of the impact of this polymorphisms on the evolution of the disease can bring us new information on TM regulation.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

Ricardo Ribeiro.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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