Genetic variations in the VEGF pathway as prognostic factors in stages II and III colon cancer

Date

10 Oct 2016

Session

Poster display

Presenters

Anna Cristina Virgili Manrique

Citation

Annals of Oncology (2016) 27 (6): 15-42. 10.1093/annonc/mdw363

Authors

A.C. Virgili Manrique1, P. Riera Armengol2, J. Salazar Blanco2, M. Tobeña1, A. Sebio Garcia1, M. Martín Richard1, E. del Rio Conde2, N. Dueñas Cid1, A. Vethencourt Casado1, A. Barba Joaquín1, M. Andrés Granyo1, D. Paez1

Author affiliations

  • 1 Medical Oncology, Hospital de la Santa Creu i Sant Pau, 08026 - Barcelona/ES
  • 2 Genetics, Hospital de la Santa Creu i Sant Pau, 08026 - Barcelona/ES
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Background

It is well known that angiogenesis plays an important role in progression and metastasis in solid tumours. We hypothesized whether genetic variations involved in this pathway may impact in stages II-III colon cancer prognosis.

Methods

We retrospectively revised 232 stage II and III colon cancer patients diagnosed between 2009 and 2014 in our institution. DNA was extracted from EDTA blood samples. A total of 27 single-nucleotide polymorphisms (SNPs) in 12 genes in the VEGF-dependent angiogenesis process were genotyped using a dynamic array on the BioMark™ system.

Results

The median age of the patients was 68.1 years (range 31-94) and 53.9% were men. One-hundred twenty-six patients were diagnosed at stage II and 106 at stage III. With a median follow-up of 37.1 months (range 9.3-91.5 months) 23.6% of patients with stage II and 30.5% with stage III relapsed. Median overall survival (OS) was 78.9 and 54.5 months for patients with stages II and III, respectively. Among the clinicopathological risk factors analysed, in the multivariate analysis, N2 (metastasis in 4 or more regional lymph nodes) was significantly associated with worse recurrence free survival (RFS) (HR: 2.56; 95% CI 1.05-6.2; adjusted p = 0.038) and OS (HR: 3.18; 95% CI 1.05-9.6; adjusted p = 0.04); and stage was also associated with worse OS (HR: 3.47; 95% CI 1.2-9.9; adjusted p = 0.019). Regarding the genetic variants analysed, in the univariate analysis, 5 polymorphisms in 4 genes (VEGFA rs1570360 A/G and rs2010963 C/G, VEGFR2 rs1551641 G/A, KRAS rs12813351 C/T and MAP2K6 rs2716191 C/T) were significantly associated with prognosis. In the multivariate analysis, patients homozygous for the variant allele of MAP2K6 rs2716191 C/T, showed significant worse prognosis in terms of RFS (HR: 1.98; 95% CI: 1.03-3.83; adjusted p = 0.041) and OS (HR: 3.38; 95% CI: 1.49-7.72; adjusted p = 0.004). Patients homozygous for the variant allele of VEGFA rs2010963 C/G showed worse OS (HR: 6.36; 95%CI 1.2-32.6; adjusted p = 0.027).

Conclusions

This study provides evidence that functional germline polymorphisms in the VEGF pathway may be helpful as prognostic biomarkers in colon cancer.

Clinical trial identification

Legal entity responsible for the study

Hospital de la Santa Creu i Sant Pau (Barcelona)

Funding

Hospital de la Santa Creu i Sant Pau (Barcelona)

Disclosure

All authors have declared no conflicts of interest.

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