What you carry at this position in your DNA and what research says about it.
Prostate Cancer Risk: 8/10 evidence, 37 publications.
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Sample genotype (not yours): A/A
Lower Overall Risk but Higher Aggressiveness Risk
This genotype is associated with a lower overall risk of developing prostate cancer and lower baseline PSA levels. However, if prostate cancer is diagnosed, it is statistically more likely to be an aggressive, higher-grade form.
What this genotype means: Lower overall risk of developing prostate cancer; Lower baseline PSA levels; Higher risk of aggressive tumor characteristics if diagnosed.
Sample genotype (not yours): A/G
Mixed Risk of Prostate Cancer Aggressiveness
This genotype is linked to a typical overall risk of developing prostate cancer but a higher risk of aggressive tumor characteristics if diagnosed. Baseline PSA levels are typically in the normal range.
What this genotype means: Typical overall risk of developing prostate cancer; Higher risk of aggressive tumor characteristics if diagnosed; Typical baseline PSA levels.
Sample genotype (not yours): G/G
Higher Overall Prostate Cancer Risk
This genotype is associated with a higher overall risk of developing prostate cancer and elevated baseline PSA levels. However, if prostate cancer does develop, it is statistically more likely to be a less aggressive, lower-grade form.
What this genotype means: Higher overall risk of developing prostate cancer; Elevated baseline PSA levels; Lower statistical likelihood of aggressive tumor characteristics if diagnosed.
Gene function and biological role
Gene Function: The KLK3 gene encodes prostate-specific antigen, a protein produced by both normal and cancerous prostate cells [1]. This protein is widely utilized as a biomarker to screen for prostate cancer and monitor its progression [1]. Genetic variations near or within the KLK3 gene can significantly influence baseline levels of this antigen in the blood, independent of the presence of cancer [2]. The gene is located on chromosome 19 in a cluster of kallikrein-related peptidases [2]. Understanding genetic influences on this gene helps refine the interpretation of screening tests [2].
Variant Impact: The rs2735839 variant is an intergenic single nucleotide polymorphism located approximately 600 base pairs downstream of the KLK3 gene [1]. This genetic change is known to modulate baseline prostate-specific antigen levels in the blood [1]. It has a dual, contrasting relationship with prostate health, affecting both the likelihood of developing prostate cancer and the aggressiveness of the disease if it occurs [3]. The major G allele is linked to higher overall susceptibility and elevated antigen levels, while the minor A allele is associated with more aggressive tumor characteristics [3].
Key Insight: The genetic variant that increases the overall risk of developing prostate cancer is actually associated with a lower risk of the cancer being aggressive if it does develop.
Location: KLK3. Chromosome 19 · 19q13.33 · 50.9 Mb
Estimated prevalence by population
Global 5.6%; European 2.0%; African 10.5%; East Asian 17.2%; South Asian 10.8%; Americas 5.3%; Ashkenazi 3.5%; Finnish 1.5%; Middle Eastern 6.7%; Amish 5.1%.
Estimated AA genotype frequency.
Global 32.5%; European 24.5%; African 43.8%; East Asian 48.6%; South Asian 44.2%; Americas 35.6%; Ashkenazi 30.5%; Finnish 21.7%; Middle Eastern 38.3%; Amish 35.0%.
Estimated AG genotype frequency.
Global 62.0%; European 73.5%; African 45.6%; East Asian 34.2%; South Asian 45.0%; Americas 59.1%; Ashkenazi 66.0%; Finnish 76.8%; Middle Eastern 55.0%; Amish 59.8%.
Estimated GG genotype frequency.
Showing effects for A/A genotype
Cancer & Oncology
Prostate Cancer
Prostate Cancer. Evidence: 8/10. Source: PMID 29892016. Lower Risk.
PSA Levels. Evidence: 6/10. Source: PMID 23269536. Lower Levels.
Cancer Prognosis & Treatment Outcome
Tumor Aggressiveness. Evidence: 3/10. Source: PMID 25715684. Increased Risk.
Showing effects for A/G genotype
Prostate Cancer. Evidence: 8/10. Source: PMID 29892016. Typical Risk.
PSA Levels. Evidence: 6/10. Source: PMID 23269536. Typical Levels.
Showing effects for G/G genotype
Prostate Cancer. Evidence: 8/10. Source: PMID 29892016. ~1.18x Higher Risk.
PSA Levels. Evidence: 6/10. Source: PMID 23269536. Elevated Levels.
Tumor Aggressiveness. Evidence: 3/10. Source: PMID 25715684. Typical Risk.
What this genotype means for the people who carry it
Sample genotype: AA (Homozygous)
Having two copies of the A allele is linked to a lower overall susceptibility to developing prostate cancer [1]. It is also associated with lower baseline levels of prostate-specific antigen in the blood, which can influence how screening results are interpreted [2]. However, this genetic profile carries a significant trade-off: if prostate cancer does develop, it is statistically more likely to be a highly aggressive form [3]. Research has shown that patients with this genotype are more frequently diagnosed with high-grade tumors, such as a Gleason score of 8 or higher, or a more aggressive Gleason 7 subtype [3]. This means that while the chance of getting the disease is lower, any detected tumors may require more prompt or intensive management. This dual effect underscores why genetic context is valuable for understanding individual prostate health.
Lower overall risk of developing prostate cancer; Lower baseline PSA levels; Higher risk of aggressive tumor characteristics if diagnosed.
Sample genotype: AG (Heterozygous)
Carrying one copy of the A allele and one copy of the G allele presents a mixed genetic risk profile for prostate health. While the overall risk of developing prostate cancer is typical compared to the general population, there is a statistical association with more aggressive disease if cancer does occur [1]. Specifically, studies of prostate cancer patients have found that carriers of the A allele are more likely to have higher Gleason scores, indicating faster-growing tumors [1]. This variant is located near the KLK3 gene, which encodes prostate-specific antigen [2]. Because the A allele is also associated with lower baseline antigen levels, it may sometimes mask early signs of disease during routine screenings [2]. This complex interplay highlights the importance of personalized risk assessment rather than relying solely on standard screening thresholds.
Typical overall risk of developing prostate cancer; Higher risk of aggressive tumor characteristics if diagnosed; Typical baseline PSA levels.
Sample genotype: GG (Homozygous)
Having two copies of the G allele is linked to a moderately increased risk of developing prostate cancer [1]. Large-scale genome-wide association studies have consistently identified the G allele as a risk factor for overall disease susceptibility [1]. This genotype is also associated with higher baseline levels of prostate-specific antigen in the blood, which can sometimes lead to detection bias during routine screenings [2]. Interestingly, while the overall risk of developing cancer is higher, research indicates that tumors in individuals with this genotype are statistically less likely to be highly aggressive [3]. This means that if cancer is diagnosed, it is more often a lower-grade, slower-growing form [3]. Understanding this genetic profile can help put screening results into a clearer context.
Higher overall risk of developing prostate cancer; Elevated baseline PSA levels; Lower statistical likelihood of aggressive tumor characteristics if diagnosed.
Variants with shared genetic architecture
rs17632542 · KLK3 Gene · Chr 19 · Prostate Cancer Risk
rs266849 · KLK3 Gene · Chr 19 · Prostate Screening
rs61752561 · KLK3 Gene · Chr 19 · Prostate Cancer Risk
Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci.
Content updated August 2026.
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