Single nucleotide polymorphisms of CYP19A1 predict clinical outcomes and adverse events associated with letrozole in patients with metastatic breast cancer View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2011-11

AUTHORS

In Hae Park, Yeon-Su Lee, Keun Seok Lee, Sook-young Kim, Seung-Hyun Hong, Jaeheon Jeong, Hyewon Lee, Jungsil Ro, Byung-Ho Nam

ABSTRACT

PURPOSE: The CYP19A1 gene encodes the aromatase enzyme involved in the peripheral conversion of androgen to estrogen. We evaluated the efficacy of the aromatase inhibitor letrozole in patients with metastatic breast cancer (MBC) as related to DNA polymorphisms of CYP19A1. PATIENTS AND METHODS: One hundred and nine patients with hormone receptor-positive MBC were treated with letrozole alone or in combination with a GnRH agonist. DNA was isolated from peripheral blood and genotyped for 46 single nucleotide polymorphisms (SNPs) of CYP19A1. RESULTS: Among 46 SNPs examined, rs700518, rs10459592, and rs4775936 were significantly associated with higher clinical benefit rate (CBR, CR + PR + SD ≥ 6 months) (OR = 2.61 [95% CI; 1.13-6.03], P = 0.025; OR = 2.45 [95% CI; 1.06-5.65], P = 0.036; OR = 2.60 [95% CI; 1.12-6.02], P = 0.026, respectively). Median time to progression (TTP) was improved without statistical significance in patients having an over-dominant form of rs700518. In haplotype analysis, the specific haplotypes M_1_3 and M_2_1 showed a strong association with CBR (OR = 3.37 [95% CI 1.43-7.90], P = 0.005; OR = 5.33 [95% CI 1.63-17.45], P = 0.006, respectively). There was a statistically significant difference in TTP in patients with haplotype M_1_3 (5.61 months [95% CI 0.00-11.45] vs. 11.08 months [95% CI 6.75-15.42], P = 0.040) and M_2_1 (7.31 months [95% CI 4.63-9.99] vs. 12.95 months [95% CI 9.27-16.63], P = 0.038). Haplotypes M_3_5 (OR = 11.25 [95% CI 1.17-108.28], P = 0.01) and M_5_3 (OR = 4.12, [95% CI 1.09-15.61], P = 0.03) were associated with side effects of arthralgia and hot flash, respectively. CONCLUSION: The genetic variations of CYP19A1 were significantly associated with clinical efficacy, suggesting potential predictive markers for letrozole treatment in patients with metastatic breast cancer. More... »

PAGES

1263-1271

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00280-011-1615-y

DOI

http://dx.doi.org/10.1007/s00280-011-1615-y

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1020977271

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/21442439


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Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1007/s00280-011-1615-y'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1007/s00280-011-1615-y'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1007/s00280-011-1615-y'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1007/s00280-011-1615-y'


 

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