Association between polymorphisms in the DNA repair genes, XRCC1, APE1, and XPD and acute side effects of radiotherapy in breast cancer patients

Jenny Chang-Claude, Odilia Popanda, Xiang Lin Tan, Silke Kropp, Irmgard Helmbold, Dietrich Von Fournier, Wulf Haase, Marie Luise Sautter-Bihl, Frederik Wenz, Peter Schmezer, Christine B. Ambrosone

    Research output: Contribution to journalArticlepeer-review

    149 Scopus citations

    Abstract

    Purpose: Several DNA repair gene polymorphisms have been described, which affect DNA repair capacity and modulate cancer susceptibility. We evaluated the association of six polymorphisms in the DNA repair genes: XRCC1 (Arg 194Trp, Arg 280His, and Arg 399Gln) , APE1 (ASp 148Glu), and XPD (Lys 751Gln and Asp 312Asn), with the risk of acute skin reactions following radiotherapy. Design: We conducted a prospective study of 446 female patients with breast cancer who received radiotherapy after breast-conserving surgery. Individual genetic polymorphisms were determined using melting point analysis of sequence-specific hybridization probes. The development of acute skin reactions (moist desquamation) associated with DNA repair gene polymorphisms was modeled using Cox proportional hazards, accounting for cumulative biologically effective radiation dose. Results: Overall, the development of acute toxicity, which presented in 77 patients, was not associated with the genetic variants studied, although the hazard ratios (HR) were generally below 1. Risks were however differential by body mass index. Among normal-weight patients only, both carriers of the APE1 148Glu and the XRCC1 399Gln alteles had decreased risk of acute skin reactions after radiotherapy (HR, 0.49 and 0.51, respectively). The results for XRCC1 were confirmed by haplotype analysis. When considering joint effects, we observed that compared with homozygote carriers of the wild-type allele in both genes, the risk was most strongly reduced in carriers of both APE1 148Glu and XRCC1 399Gln alleles with normal weight [HR, 0.19; 95% confidence interval (95% CI), 0.06-0.56] but not in those with overweight (HR, 1.39; 95% CI, 0.56-3.45; P interaction = 0.009). Conclusion: The XRCC1 399Gln or APE1 148Glu alleles may be protective against the development of acute side effects after radiotherapy in patients with normal weight.

    Original languageEnglish (US)
    Pages (from-to)4802-4809
    Number of pages8
    JournalClinical Cancer Research
    Volume11
    Issue number13
    DOIs
    StatePublished - Jul 1 2005

    All Science Journal Classification (ASJC) codes

    • Oncology
    • Cancer Research

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