Single-nucleotide polymorphisms (SNPs) associated with outcomes in patients with localized and metastatic renal cell carcinoma (RCC).

Authors

null

Carmen Garrigos

Instituto de Biomedicina de Sevilla, IBiS/Hospital Universitario Virgen del Rocio/CSIC/Universidad de Sevilla., Sevilla, Spain

Carmen Garrigos , Marta Espinosa , Ignacio Osman , Rainiero Ávila , Rafael Medina , Ricardo Melendez , Ana Salinas , Begona Perez Valderrama , Ignacio Duran

Organizations

Instituto de Biomedicina de Sevilla, IBiS/Hospital Universitario Virgen del Rocio/CSIC/Universidad de Sevilla., Sevilla, Spain, Medical Oncology Department. Hospital Universitario Virgen del Rocio., Sevilla, Spain, Hospital Universitario Virgen del Rocio, Seville, Spain, Hospital Universitario Virgen del Rocio, Sevilla, Spain, Instituto de Biomedicina de Sevilla, IBiS/Hospital Universitario Virgen del Rocio/CSIC/Universidad de Sevilla, Seville, Spain, Instituto de Biomedicina de Sevilla, IBiS/Hospital Universitario Virgen del Rocio/CSIC/Universidad de Sevilla, Sevilla, Spain

Research Funding

Other

Background: Despite major advances in the knowledge of the molecular basis of RCC, prognosis is still defined using clinical and pathological parameters. Moreover, no valid predictive biomarkers exist to help us selecting the best treatment for each patient. The aim of this work is analyzing the expression and determining the prognostic and predictive value of 64 key SNPs in 18 genes related with angiogenesis or metabolism of antiangiogenics in patients (pts) with both localized and advanced RCC treated at Hospital Universitario Virgen del Rocío. Methods: DNA from formalin fixed paraffin embedded tumor and non-tumor samples from 99 pts with RCC (26 advanced/ 73 localized) was extracted with QiAGEN Kit and amplified with a specific primers pool for every SNP as determined by the manufacturer (Lifetech). 64 SNPs were chosen based on their Minor Allele Frequency by HapMap, linkage disequilibrium by Haploview, and information from SNP data base (dSNP) and were studied by TaqMan OpenArray (Lifetech). The presence of the selected SNPs was correlated with clinical features, disease free survival (DFS), overall survival (OS), and response to treatment (RR). SPSS v16 was utilized for statistical analyses. Results: In pts with localized RCC, 6 SNPs in 3 genes involved in angiogenesis predicted for worse DFS (VEGFR2: rs10013228, rs2071559; PDGFRA: rs2228230) and shorter OS (VEGFR2: rs10013228; VEGFR3: rs6877011, rs307826) (p<0.05). In the advanced setting, 7 SNPs in genes related to both angiogenesis and metabolism of antiangiogenics determined inferior OS (IL8: rs2227543, NR1l2: rs3814055, NR1l3: rs2307424, PDGFA: rs9800958, PDGFRB: rs2302273) and worse RR (VEGFA: rs699947, rs3025010 p<0.01)). Additionally 3 SNPs in PDGFR-B and VEGF isoforms predicted for better RR (PDGFRB: rs17708574 (p=0.08), VEGFB: rs594942 (p=0.03), VEGFC: rs2016110 (p=0.07). Conclusions: Genetic analysis of RCC patients might provide valuable prognostic/predictive information. A set of SNPs in genes critical to angiogenesis and metabolism of antiangiogenics seem to determine post-surgical outcomes and treatment response in our series. These results are promising. Validation of the results is ongoing.

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Abstract Details

Meeting

2017 Genitourinary Cancers Symposium

Session Type

Poster Session

Session Title

Poster Session C: Penile, Urethral, and Testicular Cancers; Renal Cell Cancer

Track

Renal Cell Cancer,Penile, Urethral, and Testicular Cancers

Sub Track

Renal Cell Cancer

Citation

J Clin Oncol 35, 2017 (suppl 6S; abstract 437)

DOI

10.1200/JCO.2017.35.6_suppl.437

Abstract #

437

Poster Bd #

C28

Abstract Disclosures

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