Academic journal article Environmental Health Perspectives

Risk of Childhood Leukemia Associated with Diagnostic Irradiation and Polymorphisms in DNA Repair Genes

Academic journal article Environmental Health Perspectives

Risk of Childhood Leukemia Associated with Diagnostic Irradiation and Polymorphisms in DNA Repair Genes

Article excerpt

The purpose of the study was to measure risk of childhood acute lymphoblastic leukemia associated with reported postnatal diagnostic X rays and to determine if it was modified in the presence of variants in genes involved in DNA repair. We conducted a population-based case-control study with 491 cases and 491 healthy controls among children 0-9 years of age at diagnosis. To evaluate gene-environment interaction, we used a subgroup of 129 cases. The adjusted odds ratio (OR) for one reported postnatal child X ray versus none was 1.04 [95% confidence interval (CI), 0.72-1.49], whereas the OR for two or more X rays was 1.61 (CI, 1.13-2.28). Among girls, the former ORs were 1.14 (CI, 0.66-1.96) and 2.26 (1.20-4.23), respectively. Among girls who carried the hMSH3 [exon (ex) 23] variant, the ORs were 3.33 (CI, 0.75-14.82) for one X ray and 0.27 (CI, 0.05-1.57) for two or more X rays, whereas among those who carried the XRCCI (ex 6) variant, the ORs were 1.45 (0.11-19.08) and 6.66 (0.78-56.63), respectively. On the other hand, at low levels of exposure, boys seemed protected by the variant hMLH1 (ex 8). The latter results must be interpreted with caution but suggest that the effect of diagnostic X rays could be modified by variants in repair genes according to sex. Few studies have evaluated the risk of postnatal diagnostic irradiation, which was moderately strong here; we are not aware of any studies that also considered the effect of polymorphisms in DNA repair genes. Based on the present results, both aspects deserve further study. Key words: childhood leukemia, diagnostic irradiation, DNA repair genes, gene--environment interaction, polymorphisms. Environ Health Perspect 108:495-498 (2000). [Online 12 April 2000] /abstract.html

Prenatal diagnostic irradiation is a recognized risk factor for childhood cancer (1), but the risk associated with postnatal diagnostic irradiation is not well established. Excluding studies where children received radiation as a treatment, we found only a few studies that considered postnatal diagnostic X rays as a risk factor for childhood leukemia (2-8); however, their results are consistent in that reported exposure in cases was almost always more frequent than in controls.

Reduced DNA repair capacity may increase susceptibility to breast and lung cancers (9,10) as well as to hematologic malignancies. For instance, the development of leukemia and lymphoma in cases of Fanconi anemia or ataxia telangiectasia is associated with defective DNA repair (11,12). Therefore, DNA repair genes may play a key role in tumor development and in radiosensitivity. Recently, common variants were identified at the coding sequence of XRCC1 (13), a gene involved in the base excision repair (14), as well as in the DNA mismatch repair genes hMLH1 and bMSH3 (15). Although the significance of these variants is not completely clear at this time (16), it is plausible that they would be associated with altered DNA repair capacity and with modified susceptibility to cancer. We can then hypothesize that postnatal irradiation in a child with certain forms of DNA repair genes would be at increased risk of cancer.

The objectives of this study were to measure the effect of reported postnatal diagnostic irradiation on childhood acute lymphoblastic leukemia (ALL) and to carry out a preliminary study to assess whether this effect seems modified by DNA repair gene variants.

Materials and Methods

Case ascertainment. The study methods have been described by Infante-Rivard et al. (17). Cases diagnosed between 1980 and 1993 in the province of Quebec (Canada) and aged between 0 and 9 years were recruited from tertiary care centers designated by government policy to treat and hospitalize children in the province with cancer. Tracing cases from these hospitals is equivalent to a population-based ascertainment. For feasibility (cost) reasons, children living in the less populated and the most distant regions from urban centers were not included in the study. …

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