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DNA Repair Gene Variants Linked to Leukemia Outcomes

Variants associated with response to treatment, toxicity

WEDNESDAY, May 9 (HealthDay News) -- Variants in DNA repair genes are associated with response to treatment and toxicity in elderly patients with acute myeloid leukemia, researchers report in the May 1 issue of Blood.

Christine B. Ambrosone, Ph.D., from Roswell Park Cancer Institute in Buffalo, N.Y., and colleagues examined polymorphisms in the DNA repair genes APE1, XRCC1, ERCC1, XPD and XRCC3 in 200 elderly patients with acute myeloid leukemia. All patients received standard chemotherapy.

The researchers found that the XPD variant Gln751C/Asp312G ('D') haplotype was associated with a higher likelihood of complete response (odds ratio 3.06) and a lower likelihood of resistant disease (OR 0.32). ERCC1 variants were associated with a significantly lower risk of lung and metabolic toxicity, the XRCC3241Met variant was associated with a reduced risk of liver toxicity. Significant associations with other toxicities in relation to variant XPD haplotypes were also found.

"These data from clinical trials of older patients treated for acute myeloid leukemia indicate that variants in DNA repair pathways may have an impact on both outcomes of patients and toxicities associated with treatments," Ambrosone and colleagues conclude.

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