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Table 2 Genotype’s counts for the 13 variants described as related to breast cancer medications in Italian isolated populations

From: Pharmacogenetics driving personalized medicine: analysis of genetic polymorphisms related to breast cancer medications in Italian isolated populations

Snp Id
(gene)
Functional
annotation
Level of evidence Druga Minor Major Parameters Risk allele Genotype
(A1A1-A1A2-A2A2)
A
 rs4244285
(CYP2C19)
exonic,
synonymous
4 Doxorubicin, cyclophosphamide, tamoxifen A G Efficacy A (FVG freq <1000G/ExAC) 3AA-48AG-265GG
 rs714368
(SLC22A16 )
exonic,
nonsynonymous
4 Doxorubicin, doxorubicinol, cyclophosphamide C T Toxicity T (FVG freq >1000G/ExAC) 118CC-618CT-836TT
 rs4880
(SOD2)
exonic,
nonsynonymous
2B/3* Cyclophosphamide/tamoxifen A G Efficacy G (FVG freq >1000G/ExAC) 110GG-157GA-49AA
 rs1801274
(FCGR2A)
exonic,
nonsynonymous
2B Trastuzumab, doxorubicin, paclitaxel, cyclophosphamide G A Efficacy G (FVG freq <1000G/ExAC) 289GG-741GA-542AA
 rs1136201
(ERBB2)
exonic,
nonsynonymous
3 Trastuzumab G A Toxicity G (FVG freq <1000G/ExAC) 49GG - 437GA - 1095AA
 rs2297595
(DPYD)
exonic,
nonsynonymous
2A Capecitabine, fluorouracil C T Toxicity C (FVG freq <1000G/ExAC) 20CC-247CT-1314TT
 rs3918290
(DPYD)
splicing,
NA
1 Capecitabine, fluorouracil T C Toxicity T (FVG freq <1000G/ExAC) 0TT-2TC-1579CC
 rs1048943
(CYP1A1)
exonic,
nonsynonymous
3 Docetaxel, capecitabine C T Efficacy T (FVG freq >1000G/ExAC) 6CC-189CT-1386TT
 rs776746b
(CYP3A5)
splicing,
NA
3/Not reported Paclitaxel/tamoxifene T C Toxicity T (FVG freq >1000G) 18TT-216TC-1337CC
B
 rs2369049
(TCL1A)
intergenic,
NA
Not reported Exemestane, anastrozole G A Not defined Not defined 18GG-315GA-1247AA
 rs2072671
(CDA)
exonic,
nonsynonymous
Not reported Capecitabine C A Not defined Not defined 255CC-721CA-605AA
 rs180  1159
(DPYD)
exonic,
nonsynonymous
Not reported Capecitabine C T Not defined Not defined 84CC-518CT-979TT
 rs6214
(IGF1)
UTR3,NA Not reported Tamoxifen T C Not defined Not defined 198TT-707TC-666CC
  1. A) variants that show significant difference in frequency between FVG sample set and EUR/ExAC populations in terms of level of association with drug response
  2. B) variants that don’t show a level of evidence for drug response
  3. As in most case the association has been evaluated in the context of polychemotherapeutic regimens, the most likely drug related to the target polymorphism is reported in italic
  4. Snp id (gene) variant name, gene name, Functional annotation functional annotation for the variant, Level of evidence based on the amount of evidence reported at https://www.pharmgkb.org/that supports the association, Drug a medication reported to be correlated with a variant/gene after checking the literature thus filtering out the non-significative association reported in PharmGKB database, Minor minor allele, Major major allele, Genotype genotype’s count for FVG population
  5. Most of the studies were conduced in the context of polychemitherapeutic regimens; in such studies the drugs most likely related to the targeted polymorphisms according to the available literature are highlighted in italics; Parameters reported by PharmaGKB database. efficacy poor outcome, toxicity significant side effects, Risk allele risk allele reported in literature.b for variant rs776746 data for this variant was not available in the ExAC database at the time of the analysis, Genotype genotype’s counts
  6. Level 1A: annotation for a variant-drug combination in a CPIC or medical society-endorsed PGx guideline, or implemented at a PGRN site or in another major health system; Level 1B: annotation for a variant-drug combination where the preponderance of evidence shows an association. The association must be replicated in more than one cohort with significant p-values, and preferably will have a strong effect size; Level 2A: annotation for a variant-drug combination that qualifies for level 2B where the variant is within a VIP (very important pharmacogene) as defined by PharmGKB. The variants in level 2A are in known pharmacogenes, so functional significance is more likely; Level 2B: annotation for a variant-drug combination with moderate evidence of an association. The association must be replicated but there may be some studies that do not show statistical significance, and/or the effect size may be small; Level 3: annotation for a variant-drug combination based on a single significant (not yet replicated) or annotation for a variant-drug combination evaluated in multiple studies but lacking clear evidence of an association; Level 4: annotation based on a case report, non-significant study or in vitro, molecular or functional assay evidence only