X Rays and X Chromosomes.

The Leukemia Risk for Girls and Boys

Parents and health care practitioners alike cringe at the mere thought of exposing children to agents associated with cancer. For this reason, the medical world has traditionally shied away from administering prenatal X rays, long known to increase the risk of childhood leukemia. But little research has examined the effects of diagnostic X rays after birth, which are commonly prescribed by doctors. In this issue, a team of Montreal researchers takes a closer look at the underlying interactions between genes and exposure to X rays and concludes that the practice of X-raying youngsters may be putting them at increased risk, as well [EHP 108:495-498].

The team, led by McGill University medical professor Claire Infante-Rivard, first explored the link between childhood X rays and the incidence of leukemia by analyzing data collected from telephone interviews with the parents of nearly 1,000 children in Quebec, half with documented cases of leukemia. Typically, the children had received mainly bone X rays from ages five to nine. The team found that children who had received two or more X rays after birth were 1.6 times as likely to develop leukemia as children receiving no X rays. The effect was inexplicably more marked among girls: those exposed to two or more X rays more than doubled their risk of leukemia, the team reports.

The researchers probed the link further. In the first-ever effort to describe gene-environment interactions in childhood leukemia, the team examined whether inherited genetic variations, or polymorphisms, influence susceptibility to the disease. Specifically, the team looked at differences in several DNA repair genes among a subgroup of roughly 130 children who were exposed to diagnostic X rays and whose blood had been previously genotyped. They focused on four polymorphisms recently identified in three DNA repair genes.

The team found that these polymorphisms produced effects common to many gene variations; that is, they modulated the risk of children developing leukemia in a manner characteristic of polymorphisms, sometimes increasing the risk, sometimes decreasing it. Moreover, they found that the risks do not necessarily increase with higher exposures to X rays; a girl with a different mutation on a different repair gene, for instance, is actually significantly protected against leukemia upon greater exposure to X rays.

The team also determined that some polymorphisms in DNA repair genes modify risk in girls, while others modify risk in boys. Consider this: among girls, carrying a specific mutation on a repair gene and being exposed to two or more X rays results in a risk of developing leukemia that is over 6.5 times greater than the product of the risk from the mutation and the X-ray exposure. The increased risk reveals a synergistic effect between the polymorphism and exposure to X rays. Meanwhile, a boy with the same mutation and exposure actually has a reduced risk of leukemia.

Overall, the study strongly suggests that the effects of diagnostic radiation after birth may be more striking among girls. And for now, the researchers can't offer a tidy explanation for the gender differences. Infante-Rivard suggests, based on the new findings, that perhaps more caution should be exercised in prescribing X rays for both sexes and more research should be conducted on the actual dosages administered. The study authors also call for more study of polymorphisms in DNA repair genes.