Genetic polymorphisms linked to childhood acute lymphoblastic leukemia

By Will Boggs, MD

NEW YORK (Reuters Health) – Polymorphisms in the genes for three enzymes involved in biotransformation of potential carcinogens increase the risk of childhood acute lymphoblastic leukemia (ALL), according to a report in the January 10th International Journal of Cancer.

NQO1, MPO, and CYP2E1 participate in the biotransformation of a variety of xenobiotics and catalyze the formation of free radicals or protect cells from their deleterious effects, the authors explain. Whether these enzymes influence an individual's susceptibility to childhood ALL has not been investigated previously.

Dr. Daniel Sinnett, from Charles-Bruneau Cancer Center of Sainte-Justine Hospital in Montreal, Canada, and colleagues tested whether variants in the NQO1, MPO, and CYP2E1 genes affected the risk of childhood ALL in a relatively homogeneous population of French-Canadians.

Carriers of the CYP2E1*5 variant (favoring higher CYP2E1 levels) had a 2.8-fold higher risk of childhood ALL compared to those without the polymorphism, the authors report, and NQO1*2 or NQO1*3 variants (favoring lower NQO1 levels) carried a 1.7-fold increased risk.

According to the report, increased CYP2E1 levels would be expected to increase the levels of reactive oxygen species, whereas decreased NQO1 levels would be expected to increase one's susceptibility to the toxic and carcinogenic effects of certain xenobiotics.

MPO2 polymorphisms did not differ between childhood ALL patients and controls, the researchers note, but the presence of MPO*2 in combination with CYP2E1 and NQO1 variants did increase the overall risk of ALL.

"CYP2E1 and NQO1 genetic polymorphisms play a role in the development of childhood ALL," the authors conclude.

"There is a genetic contribution to the etiology of childhood leukemia," Dr. Sinnett told Reuters Health. "The underlying genetic susceptibility will be expressed when the child or the fetus is exposed to given chemicals."

"Several susceptibility genes as well as protective genes will be identified over the next years," Dr. Sinnett continued. "Only then we will start to have a better picture of the genetic susceptibility to childhood cancer."

"The gene-gene and gene-environment interactions are other aspects that will need to be addressed in the near future," Dr. Sinnett added. "Our work is oriented towards preventive medicine, i.e., prevention at the level of the population by identifying risk factors."

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