Table 3. Genetic susceptibility publications in childhood leukaemia involving genes related to cell cycle regulation, signaling, proliferation and differentiation.
| Continent | Country | Leukaemia subtype | Number of cases/controls | Age of cases(years) | Investigate dgenes | Significant results | First author, year | Reference | ||
|---|---|---|---|---|---|---|---|---|---|---|
| Genetic variation | OR (95%CI) | P-value | ||||||||
| Europe | United Kingdom | ALL | 114/414 | ≤14 | TP53, MDM2, and others(DAXX, BAT3, LTA, DDR1, IER3) |
TP53 codon 72-Arg/Pro +Pro/Pro BAT3 rs805303 BAT3 rs2077102 DAXX rs2239839-rs1059231rs2073524 |
1.67 (1.21–2.30) 0.68 (0.49–0.95) 0.62 (0.39–0.99) 2.45 (1.22–4.91) |
0.002 0.020 0.040 0.010 |
Do, 2009 | [83] |
| Germany/United Kingdom | Pre-B ALL | 1384/1877 | mean 6 | IKZF1, ARID5B, CEBPE |
IKZF1 rs4132601-AC IKZF1 rs4132601-CC ARID5B rs7089424-AC ARID5B rs7089424-CC CEBPE rs2239633-GG |
1.80 (1.50–2.00) 2.80 (2.20–3.60) 1.80 (1.50–2.10) 3.20 (2.60–4.00) 1.60 (1.30–1.90) |
<0.001 <0.001 <0.001 <0.001 <0.001 |
Prasad, 2010 | [95] | |
| Poland | ALL | 398/731 | med. 4,9 | IKZF1, ARID5B, CEBPE, CDKN2A |
IKZF1 rs4132601-G ARID5B rs7089424-G |
1.34 (1.11–1.61) 1.33 (1.10–1.61) |
0.002 0.003 |
Pastorczak, 2011 | [77] | |
| Hungary | ALL | 543/529 | 1–15 | 16 genesa |
ARID5B rs10821936 in B-ALL ARID5B rs7089424 in B-ALL ARID5B rs4506592 in B-ALL IKZF1 rs6964969 in B-ALL IKZF1 rs11978267 in B-ALL IKZF1 rs4132601 in B-ALL STAT3 rs3816769 in hyperdiploid ALL STAT3 rs12949918 in hyperdiploid ALL |
1.53 (1.26–1.85) 1.52 (1.25–1.84) 1.51 (1.24–1.83) 1.70 (1.40–2.08) 1.68 (1.38–2.05) 1.69 (1.38–2.06) 0.62 (0.49–0.79) 0.64 (0.50–0.81) |
<0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 |
Lautner-Csorba, 2012 | [43] | |
| Asia | Israel | T-ALL | 39/200 | NA | ATMTP53 |
ATM-T1229C, T1744C, T4388G ATM-C103T, -30del215, 2284delCT |
4.90 (1.20–18.20) 12.90(2.50–42.70) |
0.030 0.004 |
Liberzon, 2004 | [84] |
| China | ALL | 183/190 | mean 9.32 | CCND1 | CCND1 870AA versus. AG+GG | 3.29 (1.99–9.02) | 0.021 | Hou, 2005 | [82] | |
| China | ALL | 570/673 | 1–18 | TERT |
TERT rs2735940-TT TERT rs2853676-AG TERT rs2736100-CC TERT rs10069690-AA TERT rs4246742-TA |
1.38 (1.00–1.90) 1.36 (1.06–1.74) 1.56 (1.11–2.21) 2.00 (1.03–3.88) 0.78 (0.61–1.00) |
0.034 0.010 0.006 0.032 0.029 |
Sheng, 2013 | [85] | |
| Thailand | ALL | 190/182 | mean 6.0 | IKZF1, ARID5B, CEBPE, CDKN2A |
IKZF1 rs4132601-C ARID5B rs10821938-C inpre-B ALL |
1.57 (1.01–2.44) 0.73 (0.55–0.97) |
0.040 0.030 |
Vijayakrishnan, 2010 | [97] | |
| North America | Canada | Pre-B ALL | 240/277 | 0.4–18 | CDKN2A, CDKN2B, CDKN1A, CDKN1B |
CDKN2A -222-A CDKN2A -222-TA CDKN2B -593-T CDKN2B -1270/-593/-287CTG haplotype CDKN2B -1270/-593/-287CAG haplotype CDKN1B -1608-GA |
2.20 (1.20–4.00) 2.60 (1.10–4.30) 0.70 (0.60–1.00) 0.80 (0.60–1.00) 1.70 (1.20–2.40) 1.70 (1.00–2.80) |
0.008 0.010 0.020 0.040 0.004 0.030 |
Healy, 2007 | [16] |
| Canada | Pre-B ALL | 284/270 | med. 4.2 | ARID5B |
ARID5B rs7073837-AA ARID5B rs10994982-AA ARID5B rs10740055-CC ARID5B rs10821936-CC ARID5B rs7089424-CC ARID5B-AACCG haplotype |
2.37 (1.45–3.85) 2.29 (1.42–3.69) 2.76 (1.68–4.53) 3.11 (1.90–5.10) 3.11 (1.89–5.12) 1.93 (1.47–2.53) |
<0.001 <0.001 <0.001 <0.001 <0.001 <0.001 |
Healy, 2010 | [94] | |
| United States (Caucasians) | AML | 432/496 | <21 | MDM2 | MDM2 309-GG | 1.50 (1.03–2.20) | NA | Phillips, 2010 | [86] | |
| United States (Caucasians) | ALL | 163/251 | <21 | 23 genesb |
LMO1 rs442264 LMO1 rs442264 in B-ALL |
1.90 (1.41–2.56) 1.98 (1.44–2.73) |
<0.001 <0.001 |
Beuten, 2011 | [21] | |
| United States (Hispanics/non-Hispanics) | B-ALL | 203/414 | mean6.8/6.0 | MLL, CREBBP, TOP2A,EP300 |
MLL rs525549-AA versus AT/TT in Hispanics MLL rs6589664-GG versusAG/AA in Hispanics MLL rs6589664-AA versus AG/GG in Whites EP300 rs5758222-GG/AG versus AA in Hispanics EP300 rs7286979-AA/AG versus GG in Hispanics EP300 rs20551-AA/AG versus GG in Hispanics MLL-EP300 AG-GAA haplotype |
2.56 (1.02–6.41) 2.49 (1.23–5.04) 0.39 (0.17–0.91) 2.79 (1.46–5.32) 2.67 (1.40–5.07) 2.79 (1.26–6.18) 5.68(2.82–11.44) |
0.044 0.011 0.029 0.002 0.003 0.011 <0.001 |
Piwkham, 2011 | [87] | |
| United States (Hispanics/non-Hispanics) | ALL | 335/490 | mean 5.5/5.6 | Haplotypes of 32 genes(8 genes related to cell cycle and to poisomerase c) |
CDKN2A (rs3731257rs2518719) GG in hyperdiploid AL CDKN2A (rs3731257rs2518719) AA and GG in AL with any numerical ploidy change |
0.30 (0.14–0.64) 0.67 (0.50–0.90) 0.44 (0.26–0.73) |
0.0020.0080.001 | Chokkalingam, 2011 | [70] | |
| United States (Hispanics/non-Hispanics) | Pre-B ALL | 1308/1587 | <21 | ARID5B |
ARID5B rs10821936 in non-Hispanics ARID5B rs10821936 in Hispanics ARID5B rs7915732 in Hispanics |
2.13 (1.77–2.58) 1.92 (1.50–2.45) 2.58 (1.27–3.52) |
<0.001 <0.001 0.009 |
Xu, 2012 | [98] | |
| United States (non-Hispanics) | ALL, AML | 171/384 | <1 | IKZF1, ARID5B, CEBPE |
IKZF1 rs11978267-GG ARID5B rs10821936-C allele in ALL MLL- ARID5B rs10994982-A allele in AML MLL+ |
2.30 (1.30–4.20) 2.80 (1.60–5.00) 0.50 (0.30–0.90) |
<0.050 <0.050 <0.050 |
Ross, 2013 | [96] | |
med.: median of age.
MLL+: positive for MLL gene rearrangement.
MLL–: negative for MLL gene rearrangement.
AL: acute leukaemia.
ALL: acute lymphoblastic leukaemia.
AML: acute myeloid leukaemia.
OR: odds ratio. 95% CI: 95% confidence interval.
NA: not available.
a
ARID5B, BAX, BCL2A, BCL2B, CCR5, CEBPA, CEBPE, IKZF1, JAK1, JAK3, NOTCH1, STAT1, STAT3, STAT5A, STAT5B, STAT6.
b
BCR, ABL1, ETV6, FBXW7, LMO1, LYL1, EP300, CREBBP, MLL, JAK2, RUNX1, TCF3, CHEK2, ATM, CCND1, TOP2A, CDKN1B, IKZF1, NR3C1, TP53, BLNK, CD6, SAMSN1.
c
TP53, TP53BP1, CCND1, CDKN2A (p16), CDKN2B (p15), TOP1, TOP2A, TOP2B.