What you carry at this position in your DNA and what research says about it.
Hormone-Related Cancer Risk: 9/10 evidence, 24 publications.
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Sample genotype (not yours): C/C
Higher Breast Cancer but Lower Prostate Risk
Estrogen-receptor-negative breast cancer risk is increased with this genetic profile, while prostate cancer risk and blood pressure levels are lower.
What this genotype means: Increased risk of ER-negative breast cancer; Decreased risk of prostate cancer; Lower average blood pressure.
Sample genotype (not yours): A/A
Higher Prostate Risk but Lower Breast Cancer Risk
Prostate cancer risk and blood pressure levels are elevated, while the risk for estrogen-receptor-negative breast cancer is reduced.
What this genotype means: Increased risk of prostate cancer; Decreased risk of ER-negative breast cancer; Slightly higher average blood pressure.
Sample genotype (not yours): C/A
Typical Cancer and Blood Pressure Risk
Average risks for both prostate and breast cancers are typical for this intermediate genetic profile. Blood pressure levels also tend to remain close to the population average.
What this genotype means: Typical baseline risk for prostate cancer; Typical baseline risk for breast cancer; Average blood pressure levels.
Gene function and biological role
Gene Function: The MDM4 gene encodes a protein that acts as a critical negative regulator of the p53 tumor suppressor pathway [1]. By binding to p53, the MDM4 protein inhibits p53-mediated gene transcription, thereby preventing cell cycle arrest and apoptosis [1]. Overexpression or amplification of MDM4 is frequently observed in various human cancers, where it promotes tumor cell survival and growth [2]. Because of its direct role in suppressing p53, MDM4 is classified as an oncogene [1]. Genetic variations that alter MDM4 expression levels can significantly influence an individual's susceptibility to cancer development [2].
Variant Impact: The rs4245739 variant is located in the 3 prime untranslated region of the MDM4 gene [3]. This single nucleotide polymorphism alters a binding site for microRNAs, specifically miR-191, which regulate gene translation [3]. The minor C allele creates a high-affinity binding site for miR-191, leading to more efficient suppression of MDM4 translation and lower protein levels [4]. Conversely, the major A allele lacks this efficient binding site, resulting in higher MDM4 expression and greater inhibition of the p53 tumor suppressor [4]. This molecular difference explains why the two alleles have contrasting effects on different hormone-related cancers [3].
Key Insight: The same genetic variant that increases prostate cancer risk actually lowers the risk of aggressive estrogen-receptor-negative breast cancer.
Location: MDM4. Chromosome 1 · 1q32.1 · 204.5 Mb
Estimated prevalence by population
Global 6.1%; European 7.1%; African 5.6%; East Asian 0.1%; South Asian 6.2%; Americas 7.4%; Ashkenazi 9.6%; Finnish 1.8%; Middle Eastern 6.5%; Amish 3.8%.
Estimated CC genotype frequency.
Global 36.1%; European 39.1%; African 36.1%; East Asian 7.4%; South Asian 37.3%; Americas 39.6%; Ashkenazi 42.8%; Finnish 23.2%; Middle Eastern 38.0%; Amish 31.3%.
Estimated CA genotype frequency.
Global 57.8%; European 53.8%; African 58.3%; East Asian 92.5%; South Asian 56.5%; Americas 53.0%; Ashkenazi 47.6%; Finnish 75.0%; Middle Eastern 55.5%; Amish 64.9%.
Estimated AA genotype frequency.
Showing effects for C/C genotype
Cancer & Oncology
Prostate Cancer
Prostate Cancer. Evidence: 9/10. Source: PMID 23535732. Lower Risk.
Breast Cancer
Breast Cancer. Evidence: 8/10. Source: PMID 27117709. ~1.14x Higher Risk.
Cardiovascular & Metabolic
Hypertension
Blood Pressure. Evidence: 8/10. Source: PMID 27618452. Lower BP.
Endocrine & Reproductive
Female Reproductive Health & Fertility
Uterine Fibroids. Evidence: 6/10. Source: PMID 40050615. Lower Risk.
Showing effects for A/A genotype
Prostate Cancer. Evidence: 9/10. Source: PMID 23535732. ~1.1x Higher Risk.
Breast Cancer. Evidence: 8/10. Source: PMID 27117709. Lower Risk.
Blood Pressure. Evidence: 8/10. Source: PMID 27618452. Higher BP.
Uterine Fibroids. Evidence: 6/10. Source: PMID 40050615. Increased Risk.
Showing effects for C/A genotype
Prostate Cancer. Evidence: 9/10. Source: PMID 23535732. Typical Risk.
Breast Cancer. Evidence: 8/10. Source: PMID 27117709. Typical Risk.
Blood Pressure. Evidence: 8/10. Source: PMID 27618452. Typical BP.
Uterine Fibroids. Evidence: 6/10. Source: PMID 40050615. Typical Risk.
What this genotype means for the people who carry it
Sample genotype: CC (Homozygous)
Two copies of the minor C allele create a highly effective binding site for microRNAs like miR-191 [1]. This binding suppresses the expression of the MDM4 oncogene, allowing the p53 tumor suppressor pathway to function more effectively [1]. As a result, prostate cancer risk is significantly lower with this genetic profile [2]. Systolic and diastolic blood pressure measurements also tend to be lower compared to the major allele baseline [3]. However, large-scale genome-wide association studies have revealed a surprising flip in breast cancer susceptibility [4]. For reasons that are still being investigated, the C allele is associated with an increased risk of estrogen-receptor-negative and triple-negative breast cancers [4]. Therefore, while this profile is protective against prostate cancer and high blood pressure, it elevates the risk for specific aggressive breast cancer subtypes [4].
Increased risk of ER-negative breast cancer; Decreased risk of prostate cancer; Lower average blood pressure.
Sample genotype: AA (Homozygous)
Two copies of the major A allele lack the specialized microRNA binding site found in the C allele [1]. Without this binding site, MDM4 oncogene expression remains higher, which more actively suppresses the p53 tumor defense system [1]. Consequently, prostate cancer risk is elevated with this genetic profile [2]. Blood pressure levels, including both systolic and diastolic measurements, also tend to be slightly higher [3]. Additionally, studies suggest a higher likelihood of developing uterine fibroids [4]. However, there is a notable protective trade-off regarding breast health [5]. Large-scale genetic analyses show that the A/A profile is associated with a lower risk of estrogen-receptor-negative and triple-negative breast cancers [5]. This creates a complex health profile where prostate and cardiovascular risks are elevated, but risks for certain aggressive breast cancers are reduced [2] [5].
Increased risk of prostate cancer; Decreased risk of ER-negative breast cancer; Slightly higher average blood pressure.
Sample genotype: CA (Heterozygous)
A single copy of the C allele creates some microRNA binding sites to downregulate the MDM4 oncogene, but not to the same extent as having two copies [1]. Consequently, average or baseline risks for prostate cancer are typical for this intermediate profile [2]. Risk for estrogen-receptor-negative breast cancer is also close to the population baseline [3]. Blood pressure levels, including both systolic and diastolic measurements, typically fall within the normal average range [4]. This intermediate genetic profile means there are no highly elevated risks or strong protective effects for hormone-related conditions [2] [3]. Overall, the intermediate profile represents the typical baseline risk profile seen in the general population.
Typical baseline risk for prostate cancer; Typical baseline risk for breast cancer; Average blood pressure levels.
Variants with shared genetic architecture
rs1434536 · BMPR1B Gene · Chr 4 · Breast Cancer Risk
rs1432679 · EBF1 Gene · Chr 5 · Breast Cancer Risk
rs2242652 · TERT Gene · Chr 5 · Cancer Risk Trade-offs
MDM4 SNP34091 (rs4245739) and its effect on breast-, colon-, lung-, and prostate cancer risk.
Profile of the breast cancer susceptibility marker rs4245739 identifies a role for miRNAs.
A genetic variant of MDM4 influences regulation by multiple microRNAs in prostate cancer.
Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer.
Content updated August 2026.
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