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Blood Res (2024) 59:9
Published online March 4, 2024
https://doi.org/10.1007/s44313-024-00007-9
© The Korean Society of Hematology
Impact of CYP1A1 variants on the risk of acute lymphoblastic leukemia: evidence from an updated meta-analysis
Correspondence to : *Rim Frikha
frikha_rim@yahoo.fr
Objective Our study aimed to investigate the association between cytochrome P450 1A1 (CYP1A1) polymorphisms (T3801C and A2455G) and acute lymphoblastic leukemia (ALL) risk, considering genetic models and ethnicity.
Materials and methods PubMed, Embase, Web of Knowledge, Scopus, and the Cochrane electronic databases were searched using combinations of keywords related to CYP1A1 polymorphisms and the risk of ALL. Studies retrieved from the database searches underwent screening based on strict inclusion and exclusion criteria.
Results In total, 2822 cases and 4252 controls, as well as 1636 cases and 2674 controls of the C3801T and A2455G variants of CYP1A1, respectively, were included in this meta-analysis. The T3801C polymorphism of CYP1A1 significantly increases the risk of ALL, particularly those observed in Asian and Hispanic populations, independent of age. Similarly, the A2455G polymorphism of CYP1A1 plays a significant role in the susceptibility to ALL in all genetic models, except the heterozygous form. This association was observed mainly in mixed populations and in both children and adults (except in the heterozygous model).
Conclusion Our comprehensive analysis indicates that the T3801 and A2455G polymorphisms of CYP1A1 may increase the risk of ALL depending on ethnicity. Therefore, both variants should be considered promising biomarkers for ALL risk. Further large-scale investigations are necessary to assess other factors, such as gene-gene or gene-environment interactions.
Keywords Cytochrome, Acute lymphoblastic leukemia, Risk, Meta-analysis
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RESEARCH
Blood Res 2024; 59():
Published online March 4, 2024 https://doi.org/10.1007/s44313-024-00007-9
Copyright © The Korean Society of Hematology.
Impact of CYP1A1 variants on the risk of acute lymphoblastic leukemia: evidence from an updated meta-analysis
Imen Frikha1,2, Rim Frikha1,3*, Moez Medhaffer1,2, Hanen Charfi1,2, Fatma Turki1,3 and Moez Elloumi1,2
1Faculty of Medicine of Sfax, University of Sfax, Sfax, Tunisia
2Department of Hematology, Hedi Chaker Hospital, Sfax, Tunisia
3Department of Medical Genetics, Hedi Chaker Hospital, Sfax, Tunisia
Correspondence to:*Rim Frikha
frikha_rim@yahoo.fr
Abstract
Objective Our study aimed to investigate the association between cytochrome P450 1A1 (CYP1A1) polymorphisms (T3801C and A2455G) and acute lymphoblastic leukemia (ALL) risk, considering genetic models and ethnicity.
Materials and methods PubMed, Embase, Web of Knowledge, Scopus, and the Cochrane electronic databases were searched using combinations of keywords related to CYP1A1 polymorphisms and the risk of ALL. Studies retrieved from the database searches underwent screening based on strict inclusion and exclusion criteria.
Results In total, 2822 cases and 4252 controls, as well as 1636 cases and 2674 controls of the C3801T and A2455G variants of CYP1A1, respectively, were included in this meta-analysis. The T3801C polymorphism of CYP1A1 significantly increases the risk of ALL, particularly those observed in Asian and Hispanic populations, independent of age. Similarly, the A2455G polymorphism of CYP1A1 plays a significant role in the susceptibility to ALL in all genetic models, except the heterozygous form. This association was observed mainly in mixed populations and in both children and adults (except in the heterozygous model).
Conclusion Our comprehensive analysis indicates that the T3801 and A2455G polymorphisms of CYP1A1 may increase the risk of ALL depending on ethnicity. Therefore, both variants should be considered promising biomarkers for ALL risk. Further large-scale investigations are necessary to assess other factors, such as gene-gene or gene-environment interactions.
Keywords: Cytochrome, Acute lymphoblastic leukemia, Risk, Meta-analysis
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Table 1 . Characteristics of included studies.
First author Year of publication Ethnicity (Country) Polymorphism Study Age group Number Cases Controls Krajinovic [18] 1999 Caucasian (Canada) T3801C, A2455G Child 517 893 Gao [19] 2003 Asian (China) T3801C, A2455G Child 156 225 Balta [20] 2003 Mixed (Turky) T3801C Child 105 145 Joseph [21] 2004 Asian (India) T3801C, A2455G Child 236 236 Canalle [22] 2004 Mixed (Brazil) T3801C Child 113 221 Gallegos-Arreole [23] 2004 Mixed (Mexican) A2455G Adult 136 136 Selvin [24] 2004 Mixed (California) A2455G Child 175 175 Clavel [25] 2005 Mixed (France) T3801C Child 190 105 Liu QX [26] 2005 Asian (China) T3801C Adult 112 179 Pakakasama [27] 2005 Asian (Thailand) T3801C Child 91 320 Aydin-Sayitoglu [28] 2006 Caucasian (Turky) T3801C Adult 36 140 Aydin-Sayitoglu [28] 2006 Caucasian (Turky) T3801C Child 119 140 Bolufer [13] 2007 Caucasian (Spain) T3801C Mixt 92 403 Gallegos-Arreola [29] 2008 Hispanic (Mexican) T3801C Adult 210 228 Chen [30] 2008 Asian (China) T3801C Mixt 120 204 Lee [31] 2009 Asian (Korea) T3801C, A2455G Child 207 321 Yamaguti [14] 2010 Caucasian (Brazil) T3801C, A2455G Mixt 198 198 Swinney [32] 2011 Hispanic (USA) T3801C, A2455G Child 302 814 Swinney [32] 2011 Caucasian (USA) A2455G Child 171 437 Swinney [32] 2011 Caucasian (USA) A2455G Child 71 204 Suneetha [33] 2011 Asian (India) T3801C Child 91 150 Razmkhah [34] 2011 Mixed (Iran) A2455G Child 85 94 Bonaventure [35] 2012 Caucasian (France) T3801C Child 430 548 Agha [36] 2013 African (Egypt) T3801C, A2455G Child 558 600 Ouerhani [37] 2013 African (Tunisia) T3801C Mixt 100 106 Nida [11] 2017 Asian (India) T3801C Child 200 200
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Table 2 . Results of meta-analysis for the CYP1A1 gene T3801C polymorphisms in ALL according to the ethnicity.
Model Ethnicity Number of studies Test of association Test of heterogeneity Publication bias OR 95% CI p-val Model p-val I2 p-val (Egger’s test) Allelecontrast
(C vs. T)Overall 21 1,31 [1.08; 1.58] 0,00* Random 0,00* 75,46% 0,21 Asian 8 1,36 [1.07; 1.71] 0,00* Random 0,00* 64,87% 0,07 African 2 1,48 [0.92; 2.37] 0,10 Fixed 0,16 49,35% NA Caucasian 6 1,10 [0.91; 1.33] 0,31 Fixed 0,14 38,9% 0,47 Hispanic 2 2,22 [0.91; 5.43] 0,07 Random 0,00* 91,94% NA Mixed 3 1,05 [0.80; 1.38] 0,68 Fixed 0,66 0% 0,13 Recessive model
(CC vs. CT+TT)Overall 21 1,36 [0.86; 2.16] 0,18 Random 0,00* 72,21% 0,68 Asian 8 1,01 [0.78; 1.31] 0,92 Fixed 0,16 33,11% 0,07 African 2 2,21 [0.47; 10.44] 0,31 Fixed 0,50 0% NA Caucasian 6 0,63 [0.30; 1.33] 0,23 Fixed 0,94 0% 0,51 Hispanic 2 4,91 [1.61; 14.93] 0,00* Random 0,01* 82,35% NA Mixed 3 1,44 [0.18; 11.56] 0,72 Random 0,05 66,3% 0,77 Dominant model
(CC+CT vs. TT)Overall 21 1,40 [1.17; 1.68] 0,00* Random 0,00* 56,88% 0,56 Asian 8 1,67 [1.30; 2.15] 6,14E-05* Random 0,09 42,96% 0,44 African 2 1,43 [0.86; 2.37] 0,16 Fixed 0,18 41,92% NA Caucasian 6 1,17 [0.95; 1.44] 0,12 Fixed 0,10 45,29% 0,66 Hispanic 2 1,80 [0.71; 4.59] 0,21 Random 0,01* 84,68% NA Mixed 3 1,02 [0.75; 1.39] 0,85 Fixed 0,63 0% 0,59 Homozygous
(CC vs.TT)Overall 21 1,59 [0.99; 2.53] 0,05 Random 0,00* 68,49% 0,47 Asian 8 1,41 [0.92; 2.15] 0,10 Random 0,06 47,23% 0,11 African 2 2,27 [0.48; 10.72] 0,29 Fixed 0,47 0% NA Caucasian 6 0,67 [0.32; 1.41] 0,29 Fixed 0,96 0% 0,42 Hispanic 2 5,02 [1.26; 20.00] 0,02* Random 0,00* 86,21% NA Mixed 3 1,46 [0.19; 10.86] 0,70 Random 0,06 63,5% 0,77 Heterozygous
(CT vs. TT)Overall 21 1,38 [1.17; 1.64] 0,00* Random 0,01* 44,66% 0,55 Asian 8 1,83 [1.48; 2.25] 1,16E-08* Fixed 0,29 17,31% 0,25 African 2 1,34 [0.79; 2.27] 0,26 Fixed 0,23 27,98% NA Caucasian 6 1,22 [0.89; 1.68] 0,20 Random 0,09 47,18% 0,83 Hispanic 2 1,18 [0.81; 1.71] 0,37 Fixed 0,18 43,82% NA Mixed 3 1 [0.73; 1.37] 0,99 Fixed 0,34 05,98% 0,93 NA Not available, OR Odds ratio.
*significance (p < 0.05).
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Table 3 . Results of meta-analysis for the CYP1A1 gene T3801C polymorphisms in ALL according to the Age.
Model Age Number of studies Test of association Test of heterogeneity Publication bias OR 95% CI p-val Model p-val I2 p-val (Egger’s test) Allelecontrast
(C vsT)Overall 21 1,31 [1.08; 1.58] 0,00* Random 0,00* 75,46% 0,21 Child 14 1,27 [1.08; 1.49] 0,00* Random 0,02* 48,67% 0,20 Mixt 4 1,14 [0.76; 1.72] 0,51 Random 0,05 60,27% 0,95 Adult 3 1,57 [0.67; 3.68] 0,29 Random 0,00* 92,11% 0,50 Recessive model
(CC vs CT+TT)Overall 21 1,36 [0.86; 2.16] 0,18 Random 0,00* 72,21% 0,68 Child 14 1,26 [0.81; 1.96] 0,29 Random 0,03* 46,09% 0,57 Mixt 4 1,03 [0.63; 1.69] 0,88 Fixed 0,51 0 0,93 Adult 3 1,88 [0.28; 12.56] 0,51 Random 0,00* 93,74% 0,85 Dominant model
(CC+CT vs TT)Overall 21 1,40 [1.17; 1.68] 0,00* Random 0,00* 56,88% 0,56 Child 14 1,35 [1.12; 1.62] 0,00* Random 0,06 40,07% 0,36 Mixt 4 1,25 [0.76; 2.05] 0,37 Random 0,05 61,45% 0,99 Adult 3 1,85 [1.00; 3.41] 0,04 Random 0,03* 71,08% 0,00 Homozygous
(CC vs TT)Overall 21 1,59 [0.99; 2.53] 0,05 Random 0,00* 68,49% 0,47 Child 14 1,41 [0.90; 2.20] 0,12 Random 0,04* 42,59% 0,51 Mixt 4 1,31 [0.75; 2.28] 0,33 Fixed 0,44 0 0,91 Adult 3 2,56 [0.48; 13.57] 0,26 Random 0,00* 89,84% 0,72 Heterozygous
(CT vs TT)Overall 21 1,38 [1.17; 1.64] 0,00* Random 0,01* 44,66% 0,55 Child 14 1,38 [1.12; 1.69] 0,00* Random 0,03* 45,18% 0,28 Mixt 4 1,27 [0.78; 2.07] 0,32 Random 0,07 57,24% 0,97 Adult 3 1,59 [1.14; 2.21] 0,00* Fixed 0,11 54,17% 0,74 NA Not available, OR Odds ratio.
*significance (p < 0.05).
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Table 4 . Results of meta-analysis for the CYP1A1 gene A2455G polymorphisms and ALL risk according to the ethnicity.
Model Ethnicity Number of studies Test of association Test of Heterogeneity Publication bias OR 95% CI p-val Model p-val I2 p-val (Egger’s test) Allelecontrast
(G vs. A)Overall 12 1,25 [1.09; 1.42] 0,00* Fixed 0,14 30,92% 0,76 Caucasian 5 1,21 [0.95; 1.54] 0,11 Fixed 0,81 0,00% 0,39 Asian 3 1,36 [0.80; 2.31] 0,25 Random 0,01* 76,95% 0,11 Mixed 4 1,26 [1.03; 1.53] 0,02* Fixed 0,13 46,28% 0,69 Recessive model
(GG vs GA+AA)Overall 11 1,94 [1.39; 2.71] 0,00* Fixed 0,79 0,00% 0,58 Caucasian 5 2,03 [1.08; 3.83] 0,02* Fixed 0,78 0,00% 0,76 Asian 3 1,51 [0.81; 2.78] 0,18 Fixed 0,32 10,13% 0,45 Mixed 3 2,25 [1.35; 3.73] 0,00* Fixed 0,52 0,00% 0,46 Dominant model
(GG+GA vs AA)Overall 12 1,19 [1.01; 1.39] 0,03 Fixed 0,19 25,08% 0,77 Caucasian 5 1,13 [0.85; 1.50] 0,37 Fixed 0,72 0,00% 0,54 Asian 3 1,39 [0.75; 2.58] 0,28 Random 0,02* 71,87% 0,46 Mixed 4 1,15 [0.91; 1.46] 0,23 Fixed 0,18 38,39% 0,94 Homozygous
(GG vs AA)Overall 11 2,02 [1.43; 2.85] 0,00* Fixed 0,69 0,00% 0,65 Caucasian 5 1,92 [0.99; 3.70] 0,05 Fixed 0,86 0,00% 0,94 Asian 3 1,67 [0.88; 3.17] 0,11 Fixed 0,22 33,47% 0,46 Mixed 3 2,37 [1.41; 3.97] 0,00* Fixed 0,32 11,46% 0,60 Heterozygous
(GA vs AA)Overall 12 1,09 [0.92; 1.29] 0,3 Fixed 0,31 13,5% 0,54 Caucasian 5 1,05 [0.78; 1.42] 0,72 Fixed 0,51 0,00% 0,64 Asian 3 1,31 [0.75; 2.27] 0,33 Random 0,07 61,24% 0,35 Mixed 4 1,03 [0.80; 1.32] 0,79 Fixed 0,33 11,26% 0,77 NA Not available, OR Odds ratio.
*significance (p < 0.05).
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Table 5 . Results of meta-analysis for the CYP1A1 gene A2455G polymorphisms and ALL risk according to the age.
Model Age Number of studies Test of association Test of heterogeneity Publication bias OR 95% CI p-val Model p-val I2 p-val (Egger’s test) Allelecontrast
(G vs A)Overall 12 1,25 [1.09; 1.42] 0,00* Fixed 0,14 30,92 0,76 Child 10 1,18 [1.02; 1.37] 0,02* Fixed 0,21 24,87 0,93 Adult 1 1,75 [1.22; 2.51] 0,00* Fixed NA NA NA Mixt 1 1,25 [0.76; 2.06] 0,37 Fixed NA NA NA Recessive model
(GG vs GA+AA)Overall 11 1,94 [1.39; 2.71] 0,00* Fixed 0,79 0 0,58 Child 9 1,84 [1.27; 2.67] 0,00* Fixed 0,82 0 0,90 Adult 1 3,08 [1.32; 7.20] 0,00* Fixed NA NA NA Mixt 1 1 [0.19; 5.07] 1 Fixed NA A NA Dominant model
(GG+GA vs AA)Overall 12 1,19 [1.01; 1.39] 0,03* Fixed 0,19 25,08 0,77 Child 10 1,11 [0.93; 1.32] 0,23 Fixed 0,28 17,4 0,65 Adult 1 1,82 [1.12; 2.97] 0,01* Fixed NA NA NA Mixt 1 1,36 [0.75; 2.43] 0,30 Fixed NA NA NA Homozygous
(GG vs AA)Overall 11 2,02 [1.43; 2.85] 0,00* Fixed 0,69 0 0,65 Child 9 1,85 [1.26; 2.71] 0,00* Fixed 0,80 0 0,97 Adult 1 3,87 [1.59; 9.41] 0,00* Fixed NA NA NA Mixt 1 1,11 [0.21; 5.74] 0,89 Fixed NA NA NA Heterozygous
(GA vs AA)Overall 12 1,09 [0.92; 1.29] 0,30 Fixed 0,31 13,5 0,54 Child 10 1,01 [0.84; 1.22] 0,84 Fixed 0,37 7,55 0,42 Adult 1 1,55 [0.93; 2.57] 0,09 Fixed NA NA NA Mixt 1 1,38 [0.76; 2.52] 0,28 Fixed NA NA NA NA Not available, OR Odds ratio.
*significance (p < 0.05).
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