AI Article Synopsis
- Bevacizumab, a drug with strong anti-tumor effects, is linked to a high risk of hypertension without clear predictive markers for this condition.
- A genome-wide association study (GWAS) was conducted during the ECOG-5103 trial to identify genetic links to hypertension in patients experiencing high blood pressure while on bevacizumab treatment.
- The study found that a specific genetic variant (rs6453204) in the SV2C gene significantly predicted the occurrence of severe hypertension, confirmed in a subsequent trial (ECOG-2100).
Article Abstract
Background: Bevacizumab has broad anti-tumour activity, but substantial risk of hypertension. No reliable markers are available for predicting bevacizumab-induced hypertension.
Methods: A genome-wide association study (GWAS) was performed in the phase III bevacizumab-based adjuvant breast cancer trial, ECOG-5103, to evaluate for an association between genotypes and hypertension. GWAS was conducted in those who had experienced systolic blood pressure (SBP) >160 mm Hg during therapy using binary analysis and a cumulative dose model for the total exposure of bevacizumab. Common toxicity criteria (CTC) grade 3-5 hypertension was also assessed. Candidate SNP validation was performed in the randomised phase III trial, ECOG-2100.
Results: When using the phenotype of SBP>160 mm Hg, the most significant association in SV2C (rs6453204) approached and met genome-wide significance in the binary model (P=6.0 × 10(-8); OR=3.3) and in the cumulative dose model (P=4.7 × 10(-8); HR=2.2), respectively. Similar associations with rs6453204 were seen for CTC grade 3-5 hypertension but did not meet genome-wide significance. Validation study from ECOG-2100 demonstrated a statistically significant association between this SNP and grade 3/4 hypertension using the binary model (P-value=0.037; OR=2.4).
Conclusions: A genetic variant in SV2C predicted clinically relevant bevacizumab-induced hypertension in two independent, randomised phase III trials.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4453857 | PMC |
| http://dx.doi.org/10.1038/bjc.2014.430 | DOI Listing |
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