Cited by 287Cancer-related Molecular PathwaysEstrogen and related hormone effectsPI3K/AKT/mTOR signaling in cancer

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MDM2 SNP309 Accelerates Tumor Formation in a Gender-Specific and Hormone-Dependent Manner

Bond, Gareth L., Hirshfield, Kim M., Kirchhoff, Tomas, Alexe, Gabriella, Bond, Elisabeth E., Robins, Harlan, Bartel, Frank, Taubert, Helge, Wuerl, Peter, Hait, William, Toppmeyer, Deborah, Offit, Kenneth, Levine, Arnold J.·2006·Cancer Research

DOI 10.1158/0008-5472.can-06-0180

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Abstract

The importance of the p53 stress response pathway in the suppression of tumor formation is well documented. In a previous report, a single nucleotide polymorphism (SNP309 T/G) was found in the promoter of the MDM2 gene resulting in higher levels of MDM2 RNA and protein and, consequently, in the attenuation of the p53 pathway both in vitro and in vivo. As the SNP309 locus is found in a region of the MDM2 promoter, which is regulated by hormonal signaling pathways, and the G-allele of SNP309 increases the affinity of a well-described cotranscriptional activator of nuclear hormone receptors (i.e., Sp1), the hypothesis that the SNP309 locus could alter the effects of hormones on tumorigenesis was tested in vivo in humans. Data obtained from patients with three different sporadic cancers, from four independent case studies, support this hypothesis, providing an example for the genetic basis of gender differences in cancer and showing that the genotype at a specific locus can affect how hormones, like estrogen, affect tumorigenesis in humans.

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Authors: Bond, G. L., Hirshfield, K. M., Kirchhoff, T., Alexe, G., Bond, E. E., Robins, H., Bartel, F., Taubert, H., Wuerl, P., Hait, W., Toppmeyer, D., Offit, K., & Levine, A. J.
Affiliations: Institute for Advanced Study (US)
Rutgers Cancer Institute (US)
Memorial Sloan Kettering Cancer Center (US)
Martin Luther University Halle-Wittenberg (DE)
Universität Ulm (DE)
ORCID: Bond, Gareth L.
Hirshfield, Kim M.
Kirchhoff, Tomas
Robins, Harlan
Taubert, Helge
Toppmeyer, Deborah
Offit, Kenneth
Levine, Arnold J.
Venue: Cancer Research
Publisher: American Association for Cancer Research (AACR)
Published: 2006-05-15
Volume: 66
Issue: 10
Pages: 5104-5110
ISSN: 0008-5472 (ISSN-L)
1538-7445
DOI: 10.1158/0008-5472.can-06-0180
OpenAlex: W2131732631
Cited by: 287
References: 50
Citations by year: 2026: 1 · 2025: 2 · 2024: 3 · 2023: 6 · 2022: 6 · 2021: 6 · 2020: 7 · 2019: 9 · 2018: 8 · 2017: 10 · 2016: 9 · 2015: 12 · 2014: 21 · 2013: 17 · 2012: 24
FWCI: 18.09
Type: journal article
Language: en
Open access: closed
Locations: Cancer Research (publishedVersion)
PubMed (publishedVersion)
Funders: National Cancer Institute (P01 CA 65930-08, P01CA087497, P01CA065930, P01CA87497., T32CA099946, T32 CA 99946-01)
Topics: Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
Keywords: MDM2, SNP309, promoter polymorphism, p53 pathway, tumor formation, gender differences in cancer, estrogen, Sp1, nuclear receptors, sporadic cancer, genetic susceptibility
MeSH terms: Adolescent, Adult, Age Factors, Aged, Alleles, Breast Neoplasms, Female, Humans, Male, Middle Aged, Neoplasms, Hormone-Dependent, Sarcoma, Case-Control Studies, Lymphoma, B-Cell, Lymphoma, Large B-Cell, Diffuse, Carcinoma, Ductal, Breast, Polymorphism, Single Nucleotide, Proto-Oncogene Proteins c-mdm2

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MDM2 SNP309 Accelerates Tumor Formation in a Gender-Specific and Hormone-Dependent Manner

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