What you carry at this position in your DNA and what research says about it.
Estrogen Receptor Sensitivity: 5/10 evidence, 53 publications.
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Sample genotype (not yours): A/A
Lower Endometriosis Risk but Higher Cognitive Decline Risk
Estrogen signaling remains at a baseline level that protects reproductive tissues from overstimulation. This baseline activity is associated with typical risks for endometrial cancer but may offer less protection against age-related cognitive changes.
What this genotype means: Lower risk of endometriosis; Typical risk of tamoxifen-related blood clots; Increased risk of cognitive decline with age.
Sample genotype (not yours): A/G
Balanced Hormonal Risks with Moderate Therapy Considerations
Estrogen receptor activity is moderately altered, offering a protective effect against certain hormone-sensitive cancers. However, this intermediate sensitivity also introduces specific considerations for hormone-based medications.
What this genotype means: Reduced risk of endometrial cancer; Increased risk of tamoxifen-related blood clots; Typical risk of endometriosis.
Sample genotype (not yours): G/G
Higher Endometriosis Risk but Lower Cancer Risk
Estrogen receptor sensitivity is significantly altered, which substantially increases the risk of endometriosis and related fertility challenges. Conversely, this altered signaling provides strong protection against endometrial cancer and age-related cognitive decline.
What this genotype means: Significantly higher risk of endometriosis and related infertility; Reduced risk of endometrial cancer; Better cognitive preservation with age.
Gene function and biological role
Gene Function: Estrogen receptor 1, encoded by the ESR1 gene, is a nuclear receptor that mediates the cellular effects of the hormone estrogen [1]. It plays a fundamental role in regulating female reproductive development, bone density, cardiovascular health, and cognitive function [1] [2]. When estrogen binds to this receptor, it triggers gene transcription pathways that influence tissue growth and cellular behavior [1]. Variations in this gene can alter how efficiently cells respond to hormonal signals, impacting susceptibility to various hormone-driven conditions [2].
Variant Impact: The rs9340799 variant, historically known as the XbaI polymorphism, is located in the first intron of the ESR1 gene [3]. This genetic change does not alter the amino acid sequence of the receptor but instead influences gene expression and mRNA splicing [3]. Subtle changes in receptor abundance alter how sensitive tissues are to circulating estrogen levels [3]. Consequently, this variant has been widely studied for its impact on reproductive disorders, bone health, and response to hormone therapies [3] [4].
Key Insight: The same genetic variant that increases endometriosis risk by ten-fold actually cuts the risk of endometrial cancer in half.
Location: ESR1. Chromosome 6 · 6q25.1 · 151.8 Mb
Estimated prevalence by population
Global 47.2%; European 42.1%; African 50.9%; East Asian 63.8%; South Asian 40.0%; Americas 50.8%; Ashkenazi 37.7%; Finnish 58.8%; Middle Eastern 35.0%; Amish 46.3%.
Estimated AA genotype frequency.
Global 42.7%; European 45.6%; African 40.9%; East Asian 32.1%; South Asian 46.5%; Americas 40.9%; Ashkenazi 47.4%; Finnish 35.8%; Middle Eastern 48.3%; Amish 43.5%.
Estimated AG genotype frequency.
Global 10.1%; European 12.3%; African 8.2%; East Asian 4.0%; South Asian 13.5%; Americas 8.2%; Ashkenazi 14.9%; Finnish 5.4%; Middle Eastern 16.7%; Amish 10.2%.
Estimated GG genotype frequency.
Showing effects for A/A genotype
Endocrine & Reproductive
Female Reproductive Health & Fertility
Endometriosis. Evidence: 3/10. Source: PMID 24427778. Lower Risk.
Cancer & Oncology
Gynecological Cancers
Endometrial Cancer. Evidence: 3/10. Source: PMID 20383761. Typical Risk.
Neurology & Mental Health
Cognitive Performance
Cognitive Decline. Evidence: 3/10. Source: PMID 24150894. Increased Risk.
Pharmacogenomics
Chemotherapy Response
Tamoxifen Clot Risk. Evidence: 5/10. Source: PMID 19082882. Typical Risk.
Aromatase Inhibitor Joint Pain. Evidence: 5/10. Source: PMID 23894347. Increased Risk.
Showing effects for A/G genotype
Endometriosis. Evidence: 3/10. Source: PMID 24427778. Typical Risk.
Endometrial Cancer. Evidence: 3/10. Source: PMID 20383761. ~25% Lower Risk.
Cognitive Decline. Evidence: 3/10. Source: PMID 24150894. Typical Risk.
Tamoxifen Clot Risk. Evidence: 5/10. Source: PMID 19082882. Increased Risk.
Showing effects for G/G genotype
Endometriosis. Evidence: 3/10. Source: PMID 24427778. ~10x Higher Risk.
Endometrial Cancer. Evidence: 3/10. Source: PMID 20383761. ~47% Lower Risk.
Cognitive Decline. Evidence: 3/10. Source: PMID 24150894. ~24% Lower Risk.
Aromatase Inhibitor Joint Pain. Evidence: 5/10. Source: PMID 23894347. Typical Risk.
What this genotype means for the people who carry it
Sample genotype: AA (Homozygous)
Estrogen receptor sensitivity in this genotype helps maintain a balanced uterine environment, resulting in a significantly lower risk of developing endometriosis [1]. However, this same level of receptor activity is associated with a higher likelihood of experiencing cognitive decline during aging [2]. When undergoing breast cancer treatments, there is an increased risk of developing musculoskeletal pain from aromatase inhibitors like letrozole or anastrozole [3]. Conversely, the risk of developing dangerous blood clots during tamoxifen therapy remains at the typical baseline [4]. For individuals prescribed leflunomide for rheumatoid arthritis, this genotype is linked to a more favorable therapeutic response [5]. This response can translate to better management of joint inflammation and pain. Understanding these patterns helps paint a clearer picture of how estrogen pathways influence systemic health.
Lower risk of endometriosis; Typical risk of tamoxifen-related blood clots; Increased risk of cognitive decline with age.
Sample genotype: AG (Heterozygous)
Estrogen signaling is slightly modified in carriers of this single G allele, resulting in a typical baseline risk for endometriosis [1]. Interestingly, this moderate change in receptor function is associated with a twenty-five percent lower risk of developing endometrial cancer [2]. On the therapeutic side, there is an elevated risk of developing venous blood clots if prescribed tamoxifen [3]. Additionally, undergoing breast cancer therapy with aromatase inhibitors like letrozole may increase the likelihood of experiencing joint and muscle pain [4]. Cognitive health during aging tends to follow the typical baseline pattern seen in the general population [5]. These mixed effects highlight the complex trade-offs associated with intermediate receptor sensitivity. Individuals carrying this genotype may benefit from discussing these specific medication risks with their healthcare providers.
Reduced risk of endometrial cancer; Increased risk of tamoxifen-related blood clots; Typical risk of endometriosis.
Sample genotype: GG (Homozygous)
Estrogen receptor expression is altered in a way that highly sensitizes reproductive tissues, leading to a ten-fold increase in endometriosis risk [1]. This heightened sensitivity is also associated with a four-fold increase in endometriosis-related infertility and a higher rate of IVF failure [1]. However, this unique receptor profile offers a substantial fifty percent reduction in the risk of developing endometrial cancer [2]. Cognitive function is also better preserved with age, showing about twenty-four percent less cognitive impairment compared to other genotypes [3]. If undergoing breast cancer treatment, there is a higher risk of venous blood clots with tamoxifen, but a lower risk of joint pain from aromatase inhibitors [4] [5]. This means that alternative endocrine therapies might be preferred depending on individual clinical needs. These diverse outcomes demonstrate how a single genetic change can have vastly different effects across different organ systems.
Significantly higher risk of endometriosis and related infertility; Reduced risk of endometrial cancer; Better cognitive preservation with age.
Variants with shared genetic architecture
rs2046210 · ESR1 Gene · Chr 6 · Breast Cancer Risk
rs2077647 · ESR1 Gene · Chr 6 · Blood Pressure
rs2234693 · ESR1 Gene · Chr 6 · Bone and Heart Health
Estrogen receptor alpha polymorphisms and the risk of malignancies.
Content updated August 2026.
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