What you carry at this position in your DNA and what research says about it.
Breast Cancer Risk: 8/10 evidence, 13 publications.
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Sample genotype (not yours): G/G
Typical Breast Cancer Risk
Two copies of the common G allele are associated with typical mammographic density and average breast cancer risk.
What this genotype means: Typical mammographic density; Baseline breast cancer risk.
Sample genotype (not yours): A/A
Lower Breast Cancer Risk
Two copies of the protective A allele are associated with a more pronounced reduction in mammographic density and lower breast cancer risk.
What this genotype means: Lower mammographic density; Lower breast cancer risk.
Sample genotype (not yours): G/A
Slightly Lower Breast Cancer Risk
One copy of the protective A allele is linked to a slight reduction in mammographic density and slightly lower breast cancer risk.
What this genotype means: Slightly lower mammographic density; Slightly lower breast cancer risk.
Gene function and biological role
Gene Function: ZNF365 is a gene located on chromosome 10 that plays an important role in cell division and maintaining genomic stability. It is highly expressed in normal breast tissue and has been identified as a key locus in breast development. Research has linked variations in this gene to breast tissue composition, specifically mammographic density [1]. Mammographic density is a strong, independent risk factor for breast cancer because it reflects the proportion of dense stromal and epithelial tissues relative to fat [2]. Consequently, ZNF365 is widely studied as a major genetic modifier of breast cancer susceptibility [3].
Variant Impact: Located near the ZNF365 gene, rs10995190 is an intergenic genetic marker. This single nucleotide polymorphism involves a change from a G allele to an A allele. The change is thought to influence the expression or regulation of ZNF365 in breast tissue [1]. This regulatory shift directly impacts mammographic density, which is the amount of dense tissue visible on a mammogram [2]. Because mammographic density is closely tied to breast cancer development, this variant is also strongly associated with overall breast cancer risk [3].
Key Insight: Mammographic density is one of the strongest predictors of breast cancer risk, and this genetic variant directly influences it by altering tissue composition.
Location: ZNF365. Chromosome 10 · 10q21.2 · 62.5 Mb
Estimated prevalence by population
Global 71.8%; European 71.3%; African 68.3%; East Asian 95.6%; South Asian 83.6%; Americas 78.3%; Ashkenazi 71.5%; Finnish 60.6%; Middle Eastern 80.0%; Amish 76.5%.
Estimated GG genotype frequency.
Global 25.7%; European 26.3%; African 28.7%; East Asian 4.3%; South Asian 15.6%; Americas 20.4%; Ashkenazi 26.1%; Finnish 34.5%; Middle Eastern 18.9%; Amish 21.9%.
Estimated GA genotype frequency.
Global 2.5%; European 2.4%; African 3.0%; East Asian < 0.1%; South Asian 0.7%; Americas 1.3%; Ashkenazi 2.4%; Finnish 4.9%; Middle Eastern 1.1%; Amish 1.6%.
Estimated AA genotype frequency.
Showing effects for G/G genotype
Cancer & Oncology
Breast Cancer
Breast Cancer. Evidence: 8/10. Source: PMID 20453838. Typical Risk.
Mammographic Density. Evidence: 6/10. Source: PMID 21278746. Typical Density.
Neurology & Mental Health
Sleep & Circadian Rhythm
Sleep Chronotype. Evidence: 6/10. Source: PMID 37380357. Typical.
Showing effects for A/A genotype
Breast Cancer. Evidence: 8/10. Source: PMID 20453838. ~25% Lower Risk.
Mammographic Density. Evidence: 6/10. Source: PMID 21278746. ~4% Lower Density.
Showing effects for G/A genotype
Breast Cancer. Evidence: 8/10. Source: PMID 20453838. ~14% Lower Risk.
Mammographic Density. Evidence: 6/10. Source: PMID 21278746. ~2% Lower Density.
What this genotype means for the people who carry it
Sample genotype: GG (Homozygous)
Inheriting two copies of the G allele means possessing the standard genetic baseline for this marker. Large-scale genome-wide association studies have established that the G allele is associated with higher mammographic density compared to the protective A allele [1]. Higher mammographic density represents a greater proportion of dense epithelial and stromal tissue, which is a known risk factor for breast cancer [2]. Because this genotype lacks the protective A allele, it is linked to typical, baseline odds of developing breast cancer [3]. This baseline risk applies to both general breast cancer and estrogen receptor-negative subtypes [4]. It also represents the standard risk profile for individuals who carry BRCA2 mutations [5].
Typical mammographic density; Baseline breast cancer risk.
Sample genotype: AA (Homozygous)
Possessing two copies of the protective A allele offers the maximum genetic benefit at this specific marker. Studies indicate that each copy of the A allele progressively lowers mammographic density, resulting in a cumulative reduction of about four percent for this genotype [1]. This decrease in dense breast tissue significantly lowers the baseline risk of developing breast cancer [2]. Large-scale genome-wide association analyses consistently demonstrate that the A/A genotype is linked to the lowest odds of breast cancer compared to other genotypes at this locus [3]. This protective association holds true for both estrogen receptor-positive and estrogen receptor-negative breast cancers [4]. Additionally, this genotype helps mitigate the elevated risk typically seen in BRCA2 mutation carriers [5].
Lower mammographic density; Lower breast cancer risk.
Sample genotype: GA (Heterozygous)
Inheriting one copy of the A allele from one parent provides a modest protective effect. Research shows that each copy of the A allele is associated with approximately a two percent decrease in mammographic density [1]. Lower mammographic density means there is less dense stromal and epithelial tissue in the breast, which reduces the environment where tumors typically develop [2]. Consequently, this genotype is associated with slightly lower odds of developing breast cancer [3]. This protective effect has been replicated across multiple large-scale genetic studies [4]. The reduction in risk is also observed in individuals with BRCA2 mutations, making it a useful modifier of genetic risk [5].
Slightly lower mammographic density; Slightly lower breast cancer risk.
Variants with shared genetic architecture
rs10761659 · ZNF365 Gene · Chr 10 · Crohn's Disease Risk
rs224136 · ZNF365 Gene · Chr 10 · Crohn's Disease Risk
rs12710696 · MIR4757 Gene · Chr 2 · Breast Cancer Risk
Common variants in ZNF365 are associated with both mammographic density and breast cancer risk.
Genome-wide association study identifies five new breast cancer susceptibility loci.
Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer.
Content updated August 2026.
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