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MDM2 SNP309 and TP53 R72P associated with severe and febrile neutropenia in breast cancer patients treated with 5-FU/epirubicin/cyclophosphamide

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Abstract

The aim of this study was to investigate the association of two genetic polymorphisms, MDM2 SNP309 and TP53 R72P, with incidence of neutropenia in breast cancer patients treated with 5-FU/epirubicin/cyclophosphamide (FEC). Primary breast cancer patients (n = 216) treated with adjuvant FEC (60, 75 or 100 mg/m2) were included in this study. The association of genotypes of MDM2 SNP309 and TP53 R72P, determined by TaqMan SNP Genotyping Assays, with febrile neutropenia (FN) was investigated. In the patients treated with FEC100, G/G genotype for MDM2 SNP309 (G/G genotypeMDM2) was significantly (P < 0.01) associated with a lower incidence (5.3 vs. 39.2%) of severe neutropenia (<100/mm3) than with T/T + T/G genotypesMDM2, and C/C genotype for TP53 R72P (C/C genotypeTP53) was significantly (P = 0.03) associated with a higher incidence (58.3 vs. 27.3%) of FN than with G/G + G/C genotypesTP53. The combination of C/C genotypeTP53 and T/T + T/G genotypeMDM2 showed the highest risk for developing severe neutropenia (83.3%) and FN (62.5%) than any other combinations. In the patients treated with FEC60 or FEC75, there was no significant association of MDM2 SNP309 and TP53 R72P with severe neutropenia and FN. MDM2 SNP309 and TP53 R72P are significantly associated with severe neutropenia and FN, respectively, in breast cancer patients treated with FEC100, and especially their combination may be a useful predictor of severe neutropenia and FN.

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Acknowledgments

This study was supported in part by a Grant-in-Aid for Cancer Research from the Ministry of Health, Labour and Welfare of Japan.

Conflict of interest

S. Noguchi has received research grants and honoraria from Pfizer.

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Authors and Affiliations

  1. Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, 2-2-E10 Yamadaoka, Suita City, Osaka, 565-0871, Japan

    Masatsugu Okishiro, Seung Jin Kim, Ryo Tsunashima, Takahiro Nakayama, Kenzo Shimazu, Atsushi Shimomura, Naomi Maruyama, Yasuhiro Tamaki & Shinzaburo Noguchi

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  1. Masatsugu Okishiro
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  2. Seung Jin Kim
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  3. Ryo Tsunashima
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  4. Takahiro Nakayama
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  5. Kenzo Shimazu
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  6. Atsushi Shimomura
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  7. Naomi Maruyama
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  8. Yasuhiro Tamaki
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  9. Shinzaburo Noguchi
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Correspondence to Shinzaburo Noguchi.

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Okishiro, M., Kim, S.J., Tsunashima, R. et al. MDM2 SNP309 and TP53 R72P associated with severe and febrile neutropenia in breast cancer patients treated with 5-FU/epirubicin/cyclophosphamide. Breast Cancer Res Treat 132, 947–953 (2012). https://doi.org/10.1007/s10549-011-1637-5

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  • DOI: https://doi.org/10.1007/s10549-011-1637-5

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