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Blood, Vol. 93 No. 5 (March 1), 1999:
pp. 1496-1501
RAPID COMMUNICATION
Susceptibility to Childhood Acute Lymphoblastic Leukemia: Influence
of CYP1A1, CYP2D6, GSTM1, and GSTT1 Genetic Polymorphisms
Maja Krajinovic,
Damian Labuda,
Chantal Richer,
Sepideh Karimi, and
Daniel Sinnett
From Service d'Hématologie-Oncologie, Centre de
Cancérologie Charles-Bruneau et Centre de Recherche,
Hôpital Sainte-Justine; and Département de Pédiatrie,
Université de Montréal, Montréal, Quebec, Canada.
Although acute lymphoblastic leukemia (ALL) is the most common
childhood cancer, factors governing susceptibility to this disease have
not yet been identified. As such, ALL offers a useful opportunity to
examine the glutathione S-transferase and cytochrome P450 genes in
determining susceptibility to pediatric cancers. Both enzymes are
involved in carcinogen metabolism and have been shown to influence the
risk a variety of solid tumors in adults. To determine whether these
genes played a similar role in childhood leukemogenesis, we compared
the allele frequencies of 177 childhood ALL patients and 304 controls
for the CYP1A1, CYP2D6, GSTM1, and GSTT1 genes. We chose the French
population of Quebec as our study population because of its relative
genetic homogeneity. The GSTM1 null and CYP1A1*2A genotypes were both
found to be significant predictors of ALL risk (odds ratio
[OR] = 1.8). Those possessing both genotypes were at an even
greater risk of developing the disease (OR = 3.3). None of the
other alleles tested for proved to be significant indicators of ALL
risk. Unexpectedly, girls carrying the CYP1A1*4 were significantly
underrepresented in the ALL group (OR = 0.2), suggesting that a
gender-specific protective role exists for this allele. These results
suggest that the risk of ALL may indeed be associated with
xenobiotics-metabolism, and thus with environmental exposures. Our
findings may also explain, in part, why ALL is more prevalent among
males than females.
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