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

## TL;DR

This study shows that certain MDM2 gene variations may help breast cancer patients maintain better neutrophil levels during chemotherapy.

## Contribution

The study identifies specific MDM2 polymorphisms linked to neutrophil count stability during chemotherapy in breast cancer patients.

## Key findings

- The MDM2 SNP309 T-allele was associated with better sustained neutrophil counts (p=0.035).
- The del1518 del-allele showed a similar positive association (p=0.049).
- Combined SNP309 TT and del1518 del-allele genotypes were particularly favorable (p=0.005).

## Abstract

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.

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.

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).

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.

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

The online version contains supplementary material available at 10.1186/s12885-025-13675-2.