Vincristine-induced peripheral neuropathy (VIPN) is a debilitating side-effect of vincristine. It remains a challenge to predict which patients will suffer from VIPN. Pharmacogenomics may explain an individuals’ susceptibility to side-effects.
Gene | SNP | Allele, Major/Minor | Author and Year of Publication | MAF (%) | Number of Patients (n) | Method Effect Size | Effect Size with 95% CI (If Applicable) | Effect | |
---|---|---|---|---|---|---|---|---|---|
Cases of VIPN * | Controls * |
Transport |
ABCB1 | rs4728709 | C/T | Ceppi et al., 2014 [8] | TT/TC: 17.1 CC: 82.9 |
63 (grade 1–2) | 214 (grade 0) | Dominant OR | 0.3 (0.1–0.9) |
Gene | SNP | Author and Year of Publication | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
ABCB1 | rs1045642 | Plasschaert et al., 2004 [22], Ceppi et al., 2014 [8], Zgheib et al., 2018 [47] | Protective | 1 | |||||||||||
rs1128503 | Ceppi et al., 2014 [8], Zgheib et al., 2018 [47] | rs10244266 | T/G | Lopez-Lopez et al., 2016 [11] | 14.3 | 46 (WHO grade 1–4) | 103 (WHO grade 0) | Dominant OR | 2.60 (1.16–5.83) | ||||||
rs2032582 | Plasschaert et al., 2004 [ | Risk | 2 | ||||||||||||
22 | ] | , Ceppi et al., 2014 [8] | rs10268314 | T/C | Lopez-Lopez et al., 2016 [11] | 14.3 | |||||||||
ABCC2 | rs717620 | 27 (WHO grade 1–2) | 103 (WHO grade 0) | Dominant OR | 3.19 (1.23–8.25) | Risk | 2 | ||||||||
Zgheib et al., 2018 | [47] | rs10274587 | G/A | Lopez-Lopez et al., 2016 [11] | 14.6 | 27 (WHO grade 1–2) | 103 (WHO grade 0) | Dominant OR | 3.48 (1.36–8.86) | Risk | 2 | ||||
ACTG1 | rs1139405 | Ceppi et al., 2014 [8] | ABCC1 | rs1967120 | T/C | Lopez-Lopez et al., 2016 [11] | 27.3 | 18 (WHO grade 3–4) | 103 (WHO grade 0) | Dominant OR | 0.29 (0.09–0.99) | ||||
Protective | 2 | ||||||||||||||
rs7406609 | Ceppi et al., 2014 [8] | rs3743527 | C/T | Lopez-Lopez et al., 2016 [11] | 19.7 | 46 (WHO grade 1–4) | 103 (WHO grade 0) | Dominant OR | 0.32 (0.13–0.79) | Protective | 2 | ||||
CAPG | rs6886 | Ceppi et al., 2014 [8] | rs3784867 | C/T | Wright et al., 2019 [51] | Wright et al., 2019 [45] | 32.0 | 170 (grade 2–4) | 57 (grade 0) | Additive OR | 4.91 (1.99–12.10) | Risk | 3 | ||
CYP1A1 | rs4646903 | Abo-Bakr et al., 2017 1 [49] | rs11642957 | T/C | Lopez-Lopez et al., 2016 [11] | 48.1 | |||||||||
GSTP1 | rs1695 | Kishi et al., 2007 [13], Abo-Bakr et al., 2017 1 [49 | 46 (WHO grade 1–4) | ] | 103 (WHO grade 0) | Dominant OR | 0.43 (0.19–0.98) | Protective | 2 | ||||||
rs11864374 | G/A | Lopez-Lopez et al., 2016 [11] | 24.4 | 46 (WHO grade 1–4) | 103 (WHO grade 0) | Dominant OR | 0.35 (0.15–0.79) | Protective | |||||||
GSTT1 | 2 | ||||||||||||||
Deletion | Kishi et al., 2007 [13] | rs12923345 | T/C | Lopez-Lopez et al., 2016 [11] | 15.4 | 46 (WHO grade 1–4) | 103 (WHO grade 0) | Dominant OR | 2.39 (1.08–5.25) | Risk | 2 | ||||
MAP4 | rs11268924 | Ceppi et al., 2014 [8] | rs17501331 | A/G | Lopez-Lopez et al., 2016 | ||||||||||
[ | 11] | 13.2 | 46 (WHO grade 1–4) | 103 (WHO grade 0) | Dominant OR | 2.50 (1.10–5.68) | Risk | 2 | |||||||
rs1137524 | Ceppi et al., 2014 [8] | ABCC2 | rs12826 | G/A | Lopez-Lopez et al., 2016 [ | ||||||||||
rs1875103 | 11] | 42.6 | 46 (WHO grade 1–4) | 103 (WHO grade 0) | Dominant OR | 0.24 (0.10–0.54) | Ceppi et al., 2014 | Protective | |||||||
[ | 8 | ] | rs3740066 | G/A | Lopez-Lopez et al., 2016 [11] | 36.2 | 46 (WHO grade 1–4) | 103 (WHO grade 0) | Dominant OR | 0.23 (0.10–0.53) | Protective | ||||
rs11711953 | Ceppi et al., 2014 [8] | rs2073337 | A/G | Lopez-Lopez et al., 2016 [11] | 45.8 | 18 (WHO grade 3–4) | 103 (WHO grade 0) | Dominant OR | 0.35 (0.10–1.24) | Protective | |||||
MDR1 | Exon 21, G > T/A | Kishi et al., 2007 [13] | rs4148396 | C/T | Lopez-Lopez et al., 2016 [11] | 42.1 | 46 (WHO grade 1–4) | 103 (WHO grade 0) | Dominant OR | 0.36 (0.16–0.81) | Protective | ||||
Exon 26, C/T | Kishi et al., 2007 [13] | rs11190298 | G/A | Lopez-Lopez et al., 2016 [11] | 45.0 | 46 (WHO grade 1–4) | 103 (WHO grade 0) | Recessive OR | 2.44 (1.01–5.86) | ||||||
MTHFR | Risk | ||||||||||||||
rs1801133 | Kishi et al., 2007 [13] | ABCC1/RALPB1: miR–3117 | rs12402181 | G/A | Gutierrez–Camino et al., 2017 [48] | Gutierrez–Camino et al., 2017 [46] | 14.8 | ||||||||
rs1801131 | Kishi et al., 2007 | 19 (WHO grade 3–4) | [ | 128 (WHO grade 0) | Dominant OR | 13 | 0.13 (0.02–0.99) | Protective | 2 | ||||||
] | Vincristine metabolism | ||||||||||||||
SLC19A1 | rs1051266 | Kishi et al., 2007 [13] | CYP3A4 | rs2740574 | A/G(*1B) | Aplenc et al., 2003 [ | |||||||||
TPMT | Combined genotypes: 238GG, 460GG, 719AA/others | Kishi et al., 2007 [13]28] | 8.6 | 28 (CCG grade 3–4) | 505 (CCG grade 0–2) | Allelic OR | 0 (0–0.75) | Protective | 2 | ||||||
Guilhaumou et al., 2011 [20] | 6.3 | Nr of neurotoxicity events | Chi–square | p = 1.00 | Not significant | ||||||||||
Kishi et al., 2007 [13] | AA: 79.6 AG + GG: 20.4 |
30 (grade 2–4) | 210 (grade 0–1) | Dominant OR | 1.37 (0.57–3.29) | Not significant | |||||||||
GSTM1 | Deletion | Non–null/null | Kishi et al., 2007 [13] | Non–null: 57.5 Null: 42.5 |
30 (grade 2–4) | 210 (grade 0–1) | OR | 0.46 (0.22–0.94) | Protective | 2 | |||||
VDR | rs1544410 | G/A | Kishi et al., 2007 [13] | GG: 45.8 AA and AG: 54.2 |
30 (grade 2–4) | 210 (grade 0–1) | Recessive OR | 2.22 (1.06–4.67) | Risk | ||||||
Cytoskeleton–associated | |||||||||||||||
ACTG1 | rs1135989 | G/A | Ceppi et al., 2014 [8] | 36.5 | 38 (grade 3–4) | 214 (grade 0) | Dominant OR | 2.8 (1.3–6.3) | Risk | 1 | |||||
CAPG | rs2229668 | G/A | Ceppi et la. 2014 [8] | 12.6 | 39 (grade 3–4) | 214 (grade 0) | Dominant OR | 2.1 (1.1–3.7) | Risk | 1 | |||||
rs3770102 | C/A | Ceppi et al., 2014 [8] | 41.4 | 39 (grade 3–4) | 214 (grade 0) | Dominant OR | 0.1 (0.01–0.8) | Protective | 1 | ||||||
CEP72 | rs924607 | C/T | Diouf et al., 2015—St. Jude cohort [9] | 36.7 | 64 (grade 2–4) | 158 (grade 0) | Recessive OR | 5.5 (2.5–12.2) | Risk | ||||||
Diouf et al., 2015—COG cohort [9] | 36.4 | 22 (grade 2–4) | 74 (grade 0) | Recessive OR | Wright et al., 2019 [51] | Wright et al., 2019 [45] | TT: 13.5 CT and CC: 86.5 |
156 (grade 2–4) | 56 (grade 0) | Recessive OR | 3.4 (0.9–12.6) | Not significant | |||
Zgheib et al., 2018 [50] | Zgheib et al., 2018 [ | ||||||||||||||
TUBB | rs6070697 | Ceppi et al., 2014 [8] | |||||||||||||
rs10485828 | Ceppi et al., 2014 [8] | ||||||||||||||
TYMS | Enhancer repeat: others/3AND3 | Kishi et al., 2007 [13] | 3.8 (1.3–11.4) | Risk | |||||||||||
47 | ] | 36.9 | 23 (grade 2–4) | 107 (grade 0–1) | Recessive OR | 1.04 (0.32–3.43) | Not significant | ||||||||
MAPT | rs11867549 | A/G | Martin–Guerrero et al., 2019 [49] | Martin–Guerrero et al., 2019 [43] | 22.5 | 18 (WHO grade 3–4) | 103 (WHO grade 0) | Dominant OR | 0.21 (0.04–0.96) | Protective | 2 | ||||
SYNE2 | rs2781377 | G/A | Abaji et al., 2018—QcALL cohort [52] | Abaji et al., 2018—QcALL cohort [44] | 7.8 | 35 (grade 3–4) | 201 (grade 0) | Additive OR | 2.5 (1.2–5.2) | Risk | |||||
TUBB2B: miR–202 | rs12355840 | T/C | Martin–Guerrero et al., 2019 [49] | Martin–Guerrero et al., 2019 [43] | 23.4 | 27 (WHO grade 1–2) | 103 (WHO grade 0) | Dominant OR | 2.88 (1.07–7.72) | Risk | |||||
Hereditary neuropathy | |||||||||||||||
SLC5A7 | rs1013940 | T/C | Wright et al., 2019 [51] | Wright et al., 2019 [45] | 15.2 | 170 (grade 2–4) | 57 (grade 0) | ||||||||
UGT1A1 | Enhancer repeat: others/7AND7 | Kishi et al., 2007 [13] | |||||||||||||
VDR | rs2228570 | Kishi et al., 2007 [13] | |||||||||||||
XRCC1 | rs1799782 | Abo-Bakr et al., 2017 1 [49] | Gutierrez–Camino et al., 2016 [10] | 39.4 | 36 (WHO grade 2–4) | 106 (WHO grade 0–1) | Recessive OR | 0.7 (0.2–2.4) | Not significant | ||||||
Additive OR | 8.60 (1.68–44.15) | Risk | 3 | ||||||||||||
Other (GWAS/EWAS studies) | |||||||||||||||
BAHD1 | rs3803357 | C/A | Abaji et al., 2018—QcALL cohort [52] | Abaji et al., 2018—QcALL cohort [44] | 41.7 | 35 (grade 3–4) | 201 (grade 0) | Dominant OR | 0.35 (0.2–0.7) | Protective | |||||
COCH | rs1045466 | T/G | Li et al., 2020—POG cohort [53] | Li et al., 2020—POG cohort [48] | 38 | Maximum neuropathy score | Dominant HR | 0.27 (0.16–0.50) | Protective | ||||||
Li et al., 2020—ADVANCE cohort [53] | Li et al., 2020—ADVANCE cohort [48] | 33 | Linear regression | −3.56 (−5.45;−1.67) | Protective | ||||||||||
Chromosome 12/ chemerin | rs7963521 | T/C | Li et al., 2020—POG cohort [53] | Li et al., 2020—POG cohort [48] | 41 | Maximum neuropathy score | Additive HR | 2.23 (1.49–3.35) | Risk | ||||||
Li et al., 2020—ADVANCE cohort [53] | Li et al., 2020—ADVANCE cohort [48] | 43 | Additive HR | 2.16 (0.53–3.70) | Not significant | ||||||||||
ETAA1 | rs17032980 | A/G | Diouf et al., 2015—St. Jude cohort [9] | 26.6 | 64 (grade 2–4) | 158 (grade 0) | Allelic OR | 3.17 (1.95–5.17) | Risk | ||||||
Diouf et al., 2015—COG cohort [9] | 19.2 | 22 (grade 2–4) | 74 (grade 0) | Allelic OR | 10.4 (2.97–36.15) | Risk | |||||||||
MRPL4 | rs10513762 | C/T | Abaji et al., 2018—QcALL cohort [52] | Abaji et al., 2018—QcALL cohort [44] | 7.0 | 35 (grade 3–4) | 202 (grade 0) | Dominant OR | 3.3 (1.4–7.7) | Risk | |||||
MTNR1B | rs12786200 | C/T | Diouf et al., 2015—St. Jude cohort [9] | 22.7 | 64 (grade 2–4) | 158 (grade 0) | Allelic OR | 0.23 (0.13–0.40) | Protective | ||||||
Diouf et al., 2015—COG cohort [9] | 20.7 | 22 (grade 2–4) | 74 (grade 0) | Allelic OR | 0.24 (0.08–0.76) | Protective | |||||||||
Zgheib et al., 2018 [50] | Zgheib et al., 2018 [47] | 18.1 | 23 (grade 2–4) | 107 (grade 0–1) | Dominant OR | 0.59 (0.22–1.62) | Not significant | ||||||||
NDUFAF6 | rs7818688 | C/A | Diouf et al., 2015—St. Jude cohort [9] | 12.6 | 64 (grade 2–4) | 158 (grade 0) | Allelic OR | 4.26 (2.45–7.42) | Risk | ||||||
Diouf et al., 2015—COG cohort [9] | 14.1 | 22 (grade 2–4) | 74 (grade 0) | Allelic OR | 4.59 (1.35–15.59) | Risk | |||||||||
TMEM215 | rs4463516 | C/G | Diouf et al., 2015—St. Jude cohort [9] | 33.6 | 64 (grade 2–4) | 158 (grade 0) | Allelic OR | 3.17 (1.95–5.17) | Risk | ||||||
Diouf et al., 2015—COG cohort [9] | 24.2 | 22 (grade 2–4) | 74 (grade 0) | Allelic OR | 4.94 (1.65–14.79) | Risk | |||||||||
miRNA | |||||||||||||||
miR–4481 | rs7896283 | T/C | Gutierrez–Camino et al., 2017 [48] | Gutierrez–Camino et al., 2017 [46] | 37.5 | 19 (WHO grade 3–4) | 128 (WHO grade 0) | Dominant OR | 4.69 (1.43–15.43) | Risk | 2 | ||||
miR–6076 | rs35650931 | G/C | Gutierrez–Camino et al., 2017 [48] | Gutierrez–Camino et al., 2017 [46] | 8.7 | 47 (WHO grade 1–4) | 128 (WHO grade 0) | Dominant OR | 0.22 (0.05–0.97) | Protective | 2 |