The impact of functional MDM2-polymorphisms on neutrophil counts in breast cancer patients during neoadjuvant chemotherapy.

Background: Functional polymorphisms in the MDM2 promoters have been linked to cancer risk and several non-malignant conditions. Their potential role in bone marrow function during chemotherapy is largely unknown.

Methods: We investigated the potential associations between genotypes of MDM2 SNP309 (rs2279744), SNP285 (rs117039649) and del1518 (rs3730485) and neutrophil counts in breast cancer patients receiving neoadjuvant sequential epirubicin and docetaxel, with additional G-CSF, in the DDP-trial (NCT00496795). We applied longitudinal ratios, post vs. pre-treatment, of neutrophil counts as our main measure. Differences by genotypes were tested by Jonckheere-Terpstra test for ranked alternatives, while dominant and recessive models were tested by Mann-Whitney U test, and additional sub-analyses were performed for genotype combinations.

Results: The SNP309 reference T-allele was associated with a better sustained neutrophil count (p = 0.035). A similar association was observed for the alternative del-allele of the del1518 (p = 0.049). Additionally, in combined genotype-analyses, patients with the SNP309 TT genotype and at least one copy of the del1518 del-allele had particularly favorable sustained neutrophil counts during chemotherapy treatment (p = 0.005).

Conclusions: Our study provides evidence that MDM2 promoter polymorphisms may be associated with neutrophil counts and bone marrow recovery during chemotherapy treatment in breast cancer patients.

Trial registration: The DDP-trial was registered at ClinicalTrials.gov (NCT00496795; registration date 2007-07-04).