Term
| drugs and/or drug combinations are optimized for each individual's unique genetic makeup |
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Definition
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| sub field within pharmacogenomics refers to genetic differences in metabolic pathways which can affect individual responses to drugs, both in terms of therapeutic effect as well as adverse effects |
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| not something you're born with but something that occurs over time which results in formation of the tumor |
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| signal transduction from cell-surface receptors |
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| signal transduction from nuclear receptors |
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Definition
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Term
| potential mechanisms of varying disease risk (gene regulation): |
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Definition
| signal transduction, cell-cycle control, DNA replication/DNA repair, Metabolism/detoxification |
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Term
| microscopic DNA spots (or probes) attached to a solid surface (glass slide, silicon thin-film cell) |
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Definition
| measure the expression levels of large numbers of genes |
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| Probe-target hybridization |
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Definition
| detected/quantified by chemiluminescense |
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Term
| types of genetic variations |
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Definition
| SNPs, deletions/insertions, copy number variants (CNVs) |
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Term
| single base pair change; may result in a change of a single amino acid within the coded protein; amino acid change may affect protein activity |
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Definition
| Single nucleotide polymorphisms (SNP's) |
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Term
| doesn't change protein sequence, more than likely doesn't affect ones susceptibility/toxicity to drug because protein isn't changed, however it could affect way mRNA is translated, processed, degraded, etc |
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Definition
| Synonymous Variant Allele |
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Term
| changes the protein that is translated, this can cause significant changes |
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Definition
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| may be msall or large; single base pair change causes a frame shift in the coding region, all base pairs are affected downstream; almost always results in significant alterations in or loss of activity |
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Definition
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| increases or decreases number of alleles you have for any one gene |
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Definition
| copy number variants (CNVs) |
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Term
| Phase II detoxification enzyme; glucuronidates many xenobiotics and endogenous substrates; UDP-glucuronic acid as co-substrate |
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Definition
| Uridinediphosphate glucuronosyltransferase (UGT) 1A1 |
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Term
| causative mutation in Gilbert's syndrome; TA repeats in TATA box of the promoter which transcribes the gene, increases from 5 to 8 in *28 |
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| if you have *28/*28 it doesn't eliminate bilirubin very well |
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Definition
| if you have an injury with a lot of RBC breakage --> jaundice |
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Term
| binds to estrogen receptor and estrogen can't bind |
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Definition
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| used in estrogen receptor positive pts; post-menopausal women; breast cancer txtment--- inhibits E2 formation |
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Definition
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| hot flashes, endometrial cancer, thrombosis |
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| Tamoxifen must be metabolized to this (active metabolite) |
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Definition
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| phase I enzyme, hydroxylates variety of substrates |
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Definition
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| pts don't do as well, because they cannot make endoxifen b/c you lack activity of CYP2D6 |
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Definition
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| major phase II metabolism pathway |
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Definition
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Definition
| increases water solubility, excretion; inactivation of agent (usually); mainly hepatic |
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Term
| UDP Glucuronosyltransferases Endogenous compounds |
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Definition
| C18 and C19 steroids; bilirubin |
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Term
| UDP Gluuronosyltransferases Exogenous Compounds |
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Definition
| acetaminophen, ibuprofen, morphine; carcinogens (PAHs, nitrosamines, heterocyclic amines), chemotherapeutic agents (irinotecan, tamoxifen) |
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Term
| have individual exon 1's, basically splice onto common region of exons 2-5 so common region is identical for all the UGT's so if you have a SNP it will affect all of them |
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Definition
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| alters glucuronidation activities against TAM and its metabolites |
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Definition
| changing histadine to tyrosine |
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Term
| may be important in response to TAM |
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Definition
| combined CYP2D6 and UGT2B7 polymorphisms |
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Term
| Androstentendion --> estrone, testosterone --> estradiol via: |
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Definition
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Definition
| anastrozole, exemsestane, letrozole |
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Term
| major mode of metabolism of Exemestane (EXE) is to dihydroexemestane (DHE) |
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Definition
| can be glucoronidated due to its hydroxyl group |
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Term
| analyzing 2 alleles in the same PCR reaction; for UGT2B17 includes exon 1 AND deletion primers |
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Definition
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| much more high-throughput than multiplex PCR |
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