Identification of polymorphic variants associated with erlotinib-related skin toxicity in advanced non-small cell lung cancer patients by DMET microarray analysis
Cancer Chemotherapy and Pharmacology, ISSN: 1432-0843, Vol: 77, Issue: 1, Page: 205-209
2016
- 40Citations
- 35Captures
Metric Options: CountsSelecting the 1-year or 3-year option will change the metrics count to percentiles, illustrating how an article or review compares to other articles or reviews within the selected time period in the same journal. Selecting the 1-year option compares the metrics against other articles/reviews that were also published in the same calendar year. Selecting the 3-year option compares the metrics against other articles/reviews that were also published in the same calendar year plus the two years prior.
Example: if you select the 1-year option for an article published in 2019 and a metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019. If you select the 3-year option for the same article published in 2019 and the metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019, 2018 and 2017.
Citation Benchmarking is provided by Scopus and SciVal and is different from the metrics context provided by PlumX Metrics.
Example: if you select the 1-year option for an article published in 2019 and a metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019. If you select the 3-year option for the same article published in 2019 and the metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019, 2018 and 2017.
Citation Benchmarking is provided by Scopus and SciVal and is different from the metrics context provided by PlumX Metrics.
Metrics Details
- Citations40
- Citation Indexes40
- 40
- CrossRef24
- Captures35
- Readers35
- 35
Article Description
Purpose: Erlotinib is a targeted agent commonly used in advanced non-small cell lung cancer (aNSCLC). However, drug-related skin toxicity often may affect the quality of life of cancer patients and lead to treatment discontinuation. Genetic polymorphisms in drug transporters and metabolizing enzymes play a major role in the interindividual variability in terms of efficacy and toxicity of erlotinib treatment. The aim of our study was to identify genetic determinants in adsorption, distribution, metabolism, and excretion genes influencing skin rash (SR) by the novel drug-metabolizing enzyme and transporter (DMET) microarray Affymetrix platform in aNSCLC patients. Methods: In a retrospective study, 34 erlotinib-treated aNSCLC patients were genotyped by DMET Plus chip: 23 patients experienced SR (cases), while 11 patients did not (controls). Peripheral blood DNA was genotyped. Genotype association was analyzed by Fisher's exact test, and the toxicity-associated gene sets underwent Ingenuity Pathway Analysis (IPA). Results: Seven SNPs in six genes (CYP27B1, MAT1A1, CHST1, CYP4B1, ADH6, and SLC22A1) were associated with the occurrence of SR or with a protective effect. Specifically, the rs8176345 in CYP27B1 gene was significantly correlated with SR (p = 0.0003, OR 55.55, 95 % CI 2.7036-1141.1707). The IPA on SR-related genes highlighted the role of a variety of canonical pathways including 1,25-dihydroxyvitamin D3 biosynthesis, S-adenosyl-l-methionine biosynthesis, and methionine degradation I (to homocysteine) in SR development. Conclusion: Although exploratory, this study indicates rs8176345 in CYP27B1 gene as significantly correlated with erlotinib-induced SR in aNSCLC patients probably through a mechanism mediated by vitamin D3 and inflammation at skin level.
Bibliographic Details
http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84954077107&origin=inward; http://dx.doi.org/10.1007/s00280-015-2916-3; http://www.ncbi.nlm.nih.gov/pubmed/26607259; http://link.springer.com/10.1007/s00280-015-2916-3; https://dx.doi.org/10.1007/s00280-015-2916-3; https://link.springer.com/article/10.1007/s00280-015-2916-3; http://link.springer.com/article/10.1007/s00280-015-2916-3; https://link.springer.com/content/pdf/10.1007%2Fs00280-015-2916-3.pdf; http://link.springer.com/content/pdf/10.1007/s00280-015-2916-3.pdf; https://link.springer.com/content/pdf/10.1007/s00280-015-2916-3.pdf; http://link.springer.com/article/10.1007/s00280-015-2916-3/fulltext.html; http://link.springer.com/article/10.1007%2Fs00280-015-2916-3; http://link.springer.com/content/pdf/10.1007/s00280-015-2916-3
Springer Science and Business Media LLC
Provide Feedback
Have ideas for a new metric? Would you like to see something else here?Let us know