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

IF 3.4 2区医学 Q2 ONCOLOGY

BMC Cancer Pub Date : 2025-02-20 DOI:10.1186/s12885-025-13675-2

Nora D Hatletvedt, Christina Engebrethsen, Jürgen Geisler, Stephanie Geisler, Turid Aas, Per E Lønning, Liv B Gansmo, Stian Knappskog

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引用次数: 0

Abstract

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).

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背景：MDM2启动子的功能多态性与癌症风险和一些非恶性疾病有关。它们在化疗过程中对骨髓功能的潜在作用尚不清楚：我们研究了在 DDP 试验（NCT00496795）中接受新辅助序贯表柔比星和多西他赛以及额外 G-CSF 的乳腺癌患者中，MDM2 SNP309 (rs2279744)、SNP285 (rs117039649) 和 del1518 (rs3730485) 的基因型与中性粒细胞计数之间的潜在关联。我们采用治疗后与治疗前中性粒细胞计数的纵向比率作为主要衡量指标。基因型的差异通过 Jonckheere-Terpstra 检验进行排序替代检验，显性和隐性模型通过 Mann-Whitney U 检验进行检验，并对基因型组合进行了额外的子分析：结果：SNP309 的参考 T-等位基因与更好的持续中性粒细胞计数相关（p = 0.035）。在 del1518 的替代 del-等位基因中也观察到类似的关联（p = 0.049）。此外，在联合基因型分析中，SNP309 TT基因型和至少一个del1518 del-等位基因拷贝的患者在化疗期间的持续中性粒细胞计数特别好（p = 0.005）：我们的研究提供了证据，表明MDM2启动子多态性可能与乳腺癌患者化疗期间的中性粒细胞计数和骨髓恢复有关：DDP试验已在ClinicalTrials.gov网站注册（NCT00496795；注册日期2007-07-04）。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

BMC Cancer 医学-肿瘤学

CiteScore

6.00

自引率

2.60%

发文量

1204

审稿时长

6.8 months

期刊介绍： BMC Cancer is an open access, peer-reviewed journal that considers articles on all aspects of cancer research, including the pathophysiology, prevention, diagnosis and treatment of cancers. The journal welcomes submissions concerning molecular and cellular biology, genetics, epidemiology, and clinical trials.