Maternal smoking during pregnancy, genetic polymorphisms of metabolic enzymes, and childhood acute leukemia: the ESCALE study (SFCE).
OBJECTIVE
This study explored interactions between prenatal exposure to maternal smoking and polymorphisms in metabolic genes in the risk of childhood acute leukemia (AL).


METHODS
The data were generated by the ESCALE study, which included 764 AL cases and 1,681 controls in 2003-2004. The data on maternal smoking during pregnancy were obtained by standardized telephone interview of the cases' and controls' mothers. The genotypes CYP1A1*2A/2B (rs4646903), CYP2E1*5 (rs2031920, rs3813867), NQO1*2 (rs1800566), NAT2*5 (rs1801280), and EPHX1 exon 3 (rs1051740) and exon 4 (rs2234922) were obtained using a high-throughput platform and imputation for untyped polymorphisms. The analyses were restricted to the 493 cases (433 cases of lymphoblastic (ALL) and 51 of myeloblastic (AML) leukemia) and 441 controls with at least 2 grandparents born in Europe, who were genotyped with individual call rates greater than 95%. Odds ratios were estimated by logistic regression in case-control analyses and, for gene-gene and gene-environment interactions, by case-only analyses.


RESULTS
ALL and AML were not associated with either maternal smoking during pregnancy or candidate polymorphisms in CYP1A1, CYP2E1, EPHX1, and NQO1. Carrying two NAT2*5 alleles was significantly associated with ALL (OR = 1.8 [1.3-2.5]). The analyses also suggested an interaction between three genes involved in benzene metabolism CYP2E1, NQO1, and EPHX1. There was no interaction between maternal smoking and any of the polymorphisms under study.


CONCLUSIONS
The ESCALE study did not evidence the interaction between CYP1A1*2A/2B and maternal smoking suggested previously. The association with NAT2*5 and the gene-gene interactions need to be replicated.
Inserm, UMRS 1018, CESP, Team 6 Environmental Epidemiology of Cancer, Villejuif, France. audrey.bonaventure@inserm.fr
Audrey
A
Bonaventure
Stéphanie
S
Goujon-Bellec
Jérémie
J
Rudant
Laurent
L
Orsi
Guy
G
Leverger
André
A
Baruchel
Yves
Y
Bertrand
Brigitte
B
Nelken
Marlène
M
Pasquet
Gérard
G
Michel
Nicolas
N
Sirvent
Pierre
P
Bordigoni
Stéphane
S
Ducassou
Xavier
X
Rialland
Diana
D
Zelenika
Denis
D
Hémon
Jacqueline
J
Clavel
D000293:Adolescent; D000483:Alleles; D001554:Benzene / Q000378:metabolism; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D000072467:Cytochrome P450 Family 2; D004851:Epoxide Hydrolases / Q000235:genetics; D005060:Europe; D005091:Exons / Q000235:genetics; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods; D005838:Genotype; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000201:enzymology* / Q000235:genetics* / Q000378:metabolism; D016015:Logistic Models; D008297:Male; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011252:Pregnancy Complications, Neoplastic / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D011297:Prenatal Exposure Delayed Effects / Q000201:enzymology* / Q000235:genetics* / Q000378:metabolism; D012907:Smoking / Q000009:adverse effects*
D003577:Cytochrome P-450 Enzyme System; C569463:CYP1A1 protein, human; C110332:CYP2F1 protein, human; D019363:Cytochrome P-450 CYP1A1; D000072467:Cytochrome P450 Family 2; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; D004851:Epoxide Hydrolases; C522330:EPHX1 protein, human; D001554:Benzene