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Table 1 Select examples of SNPs with clinical significance.

From: Genotyping panel for assessing response to cancer chemotherapy

Phase I metabolism enzymes,
Allele nomenclature for Cytochrome P450 enzymes [24]:
Gene rs# location Function SNPlex
CYP2C9 rs1799853 *2, R144C PM 0.25% in Caucasians, life-threatening bleeding after given warfarin No
  rs1057910 *3, I359L   Yes
CYP2C19 rs4244285 *2, 681G>A, exon 5, splicing defect PM phenotype 2–5% in Caucasians, 18–23% in Asians, > 87% PM in Caucasians is *2 and *3; > 99% PM in Asians has *2 and *3. CYP2C19*2 homozygotes did not respond to antiangiogenic drug thalidomide treatment No
  rs4986893 *3, 17948G>A, exon 4 premature stop   Yes
  rs28399504 *4, transcription ablation   Failed
   90033C>T, R433W, *5A, *5B No enzymatic activity Yes
   *7, 19294T>A Splicing defect, no enzymatic activity Yes
CYP2D6 rs16947 *2, 2851C>T, R296C Normal, nucleotide position corrected according to [47] Yes
  rs3892097 or rs1800716 *4, 1847G>A, splicing defect The CYP2D6 PM is about 5–10% of Caucasians. 99% PM has *3, *4, *5, *6, *7, *8 and *11. *3, *5 and *6 are deletions Yes
  rs28371704 983A>G, H94R In *4A, *4B, *4F, *4G, *4H and *4J Failed
  rs5030867 *7, 2936A>C, H324P No enzymatic activity Yes
  rs5030865 *8, 1759G>T Stop codon, no enzymatic activity Yes
  rs1065852 *10, 100C>T, P34S Decrease enzymatic activity Yes
  rs5030863 *11, 882G>C Splicing defect, no enzymatic activity Yes
  rs28371706 *17, 1022C>T, T107I Decrease enzymatic activity Yes
  rs28371717 *33, 2484G>T, A237S Normal Yes
   *44, 2951G>C Splicing defect, no enzymatic activity Yes
CYP3A4 rs11773597 *1F, m747C>G Trans-regulation of gene expression is important. Overall, no major pharmacokinetic consequences for the identified CYP3A4 SNPs have been observed for the metabolism of anti-cancer drugs [12] Yes
  rs2740574 *1B, m392A>G   Yes
   *4, 13989A>G, In AF209389 Yes
   *8, 14026G>A In AF209389, R130Q Yes
CYP3A5 rs28365083 *2, 27289C>A, T398N   Failed
  rs776746 *3, 6986A>G, splicing inclusion *3 is the most frequent polymorphism (about 90% in Caucasians). Splicing defect, severely decrease of enzymatic activity [12] Yes
  rs28365085 *3d, 31551T>C, I488T   Yes
   *5, 12952T>C Splicing defect Yes
   *8, 3699C>T, R28C Decreased enzymatic activity Yes
  rs28383479 *9, 19386G>A, A337T Decreased enzymatic activity Failed
  rs15524 *10, 31611C>T Decreasde enzymatic activity Yes
DPYD rs3918290 splice variant IVS14+1G>A *2A, Skipping exon 14, ↑ 5FU neurotoxicity [12] Yes
NQO1 rs1800566 *2, C609T, R187S *2 and *3 have reduced protein level and enzymatic activity. NQO1 is needed for the activation of mitomycin C, 17AAG (HSP90 inhibitor) and inactivation of benzene-like leukemogenic agents [13] Yes
  rs4986998 *3, C465T, R139W   Yes
Phase II metabolism enzymes
NAT allele nomenclature [26]:
UGT allele nomenclature [25]:
Gene rs# location Function SNPlex
NAT2 rs1801280 341T>C, I114T, *5A to*5J, *14C and *14F Alleles with decreased activity include NAT2*5B, NAT2*6A, NAT*7A or B, NAT2*10, NAT2*14A or B, NAT2*17, NAT2*18 and NAT2*19 [12, 14]
Low NAT2 activity is related to the increased risk of isoniazid hepatotoxicity
  rs1799929 481C>T, L161L, *5A, *5B, *5F, *5G, *5H, *5I, *6E, *11A, *11B, *12C and *14C   Yes
  rs1208 803A>G, K268R,*5B, *5C, *5F, *5G, *5H, *5I, *6C, *12A, *12B, *12C, *12D, *14E and *14F   Yes
  rs1041983 282C>T, Y94Y, *13, *5G, *5J, *6A, *6C, *6D, *7B, *12B, *14B, *14D, *14G   Yes
  rs1799930 590G>A, R197Q *5E, *5J, *6A, *6B to *6E, *14D   Yes
  rs1799931 , 857G>A, G286E *7A, *7B   Yes
   499G>A in sequence X14672, E167K, *10   Yes
  rs1801279 191G>A, R64Q *14A to *14G,   Yes
   434A>C A in sequence X14672, Q145P, *17   Yes
   845A>C A in sequence X14672, K282T, *18   Yes
  rs1805158 190C>T, R64W, *19   Yes
TPMT rs1800462 *2, 238G>C Null genotype associated with hematopoietic thiopurine toxicity, homozygous frequency 1/300 [4] No
  rs1800460 *3A, 460G>A   No
  rs1142345 *3C, 719A>G   No
UGT1A1   TA (5–8) TAA UGT1A1 *28 (7 TAs) associated with increased irinotecan toxicity. Caucasians ~32% No
  rs4148323 211G>A, G71R, *6 Reduced enzymatic activity Yes
  rs34993780 1456T>G, Y486D, *7   Yes
  rs35350960 686C>A, P229Q, *27   Yes
   247T>C, F83L, *62 Causing Gilbert's syndrome Yes
GSTT1   Deletion causing null genotype Null allele has been associated with better or poorer survival in leukemia patients following chemotherapy [12] No
GSTP1 rs947894 313A>G I105V Val associated with decreased enzyme activity and increased survival after 5FU/oxaliplatin treatment of colorectal cancer patients [54] Yes
GSTM1   Deletion causing null genotype Null allele is associated with increased survival after chemotherapy for multiple cancers [13, 14] No
SULT1A1 rs9282861 *2, R213H, HaeII His/His has lower enzymatic activity and is associated with poor survival following tamoxifen therapy [55] No
Transporter Genes
Gene rs# location Function SNPlex
ABCB1 rs1045642 3435C>T C3435 associated with higher drug transport activity Yes
  rs1128503 1236T>C   Yes
  rs2229109 1199G>A   Yes
ABCC2 rs2273697 1249G>A, Val417Ile 1249AA associated with decreased mRNA [56] Yes
ABCG2 rs2231142 421C>A, Q141K Minor alleles with lower BRCP expression, enhanced drug sensitivity [12] Yes
  rs2231137 G34 G>A V12M   No
   944–949 deletion   No
SLC19A1 rs1051266 80G>A Arg27His Patients with the 80AA genotype had higher plasma MTX levels, suggesting decreased cellular uptake of MTX Yes
SLCO1B1/SCL21A6 rs4149056 T521C, Val174Ala, *5 *5 and *15 are associated with decreased transport activity [57] Yes
  rs2306283 Asp130Asn, *15   Yes
DNA repair genes
Gene rs# location Function SNPlex
BRCA2 rs144848 N372H Cancer risk [51] Yes
OGG1 rs1052133 S326C Cancer risk [51] Yes
XRCC1 rs1799782 R194W Cancer risk [51] Yes
  rs25487 R399Q Gln399 associated with oxaliplatin/5-FU resistance Yes
  rs25489 R280H   Yes
ERCC2/XPD rs13181 K751Q Lys751 associated with improved oxaliplatin/5-FU treatment outcome [52] Yes
TP53 rs1042522 R72P Cancer risk Failed
MGMT rs12917 262C>T, L84F Decreased repair of DNA damage [58] Yes
CHEK2   1100delC Protein truncation, cancer risk [59] No
Drug target, pathway genes
Gene rs# location Function SNPlex
DHFR rs5030762 829T>C SNP 829T>C located in the untranslated region of the DHFR, associated with ↑ of DHFR mRNA, ↓ responsiveness to methotrexate No
MTHFR rs1801133 677C>T, A222V minor allele frequency 24–46%% in Caucasians, T allele is associated with reduced enzyme activity, increased toxicity to methotrexate [13, 53] Yes
  rs1801131 1298A>C, E429A Reduced MTHFR enzyme activity [13, 53] Yes
TYMS   2–9 28 bp repeats in the 5' promoter enhancer 3 repeats ↑ RNA, TSER*3 associated with drug resistance of 5FU and methotrexate No
CDA rs2072671 79A>C, K27Q Minor allele has lower activity to inactivate gemcitabine than the wild-type [60] Yes
   208G>A, A70T 70TT has lower activity to inactive cytidine and ara-C than the wild-type [61] Yes
Cell cycle genes
CCND1 rs603965 870A>G Alternative transcript encodes a protein with enhanced cell transformation activity, and modifies caner risk [62] Yes