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Gynecologic oncology v.147 no.3, 2017년, pp.621 - 625   SCI SCIE
본 등재정보는 저널의 등재정보를 참고하여 보여주는 베타서비스로 정확한 논문의 등재여부는 등재기관에 확인하시기 바랍니다.

Genetic predisposition to bevacizumab-induced hypertension

Frey, Melissa K. (Weill Cornell Medicine, New York, NY, United States ) ; Dao, Fanny (New York University Langone Medical Center, New York, NY, United States ) ; Olvera, Narciso (New York University Langone Medical Center, New York, NY, United States ) ; Konner, Jason A. (Memorial Sloan Kettering Cancer Center, New York, NY, United States ) ; Dickler, Maura N. (Memorial Sloan Kettering Cancer Center, New York, NY, United States ) ; Levine, Douglas A. (New York University Langone Medical Center, New York, NY, United States ) ;
  • 초록  

    Abstract Objective Bevacizumab, a monoclonal antibody to VEGF, has shown efficacy in ovarian, cervical and endometrial cancer in addition to several other solid tumors. Serious side effects include hypertension, proteinuria, bowel perforation, and thrombosis. We tested the hypothesis that genetic variation in hypertension-associated genes is associated with bevacizumab-induced hypertension (BIH). Methods Patients with solid tumors treated with bevacizumab in combination with other therapy were identified from six clinical trials. Haplotype-tagging (ht) SNPs for 10 candidate genes associated with hypertension were identified through the International Hapmap Project. Germline DNA was genotyped for 103 htSNPs using mass spectrometry. Bevacizumab toxicities were identified from clinical trial reports. Haplotypes were reconstructed from diploid genotyping data and frequencies were compared using standard two-sided statistical tests. Results The study included 114 patients with breast, lung, ovarian, or other cancers, of whom 38 developed BIH. WNK1 , KLKB1 , and GRK4 were found to contain single loci associated with BIH. Haplotype analysis of WNK1 , KLKB1 , and GRK4 identified risk haplotypes in each gene associated with grade 3/4 BIH. A composite risk model was created based on these haplotypes. Patients with the highest risk score were the most likely to develop grade 3/4 BIH (OR=6.45; P = 0.005; 95%CI, 1.86–22.39). Conclusions We concluded that genetic variation in WNK1 , KLKB1 , and GRK4 may be associated with BIH. These genes are biologically plausible mediators due to their role in blood pressure control, regulating sodium homeostasis and vascular tone. This preliminary risk model performed better than population-based risk models and when further validated may help risk-stratify patients for BIH prior to initiating therapy. Highlights Variation in WNK1 , KLKB1 , and GRK4 may be associated with BIH. WNK1 , KLKB1 , and GRK4 are biologically plausible mediators of BIH. A composite risk model identified 43% of patients who developed BIH.


  • 주제어

    Bevacizumab .   Hypertension .   Haplotype .   WNK1 .   KLKB1 .   GRK4.  

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