What you carry at this position in your DNA and what research says about it.
Liver Cancer Risk: 4/10 evidence, 28 publications.
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Sample genotype (not yours): A/A
Typical Cancer Risk
Typical levels of epidermal growth factor production characterize this genetic profile. It lacks the elevated risks for liver, brain, or gallbladder cancers linked to the G variant.
What this genotype means: Typical EGF protein levels; Lower risk of liver cancer; Typical risk of glioma.
Sample genotype (not yours): A/G
Increased Risk of Liver and Brain Tumors
Presence of one G allele is linked to higher epidermal growth factor production. This increases susceptibility to liver cancer in individuals with chronic liver disease, as well as brain tumors.
What this genotype means: Elevated EGF protein levels; Higher risk of liver cancer with cirrhosis; Increased risk of glioma.
Sample genotype (not yours): G/G
Higher Risk of Liver, Brain, and Gallbladder Tumors
Two copies of the G allele lead to the highest production of epidermal growth factor. This is linked to elevated risks for liver cancer under chronic inflammation, brain tumors, and gallbladder cancer in females.
What this genotype means: Highest baseline EGF protein levels; Higher risk of liver cancer with cirrhosis; Increased risk of glioma.
Gene function and biological role
Gene Function: The EGF gene encodes epidermal growth factor, a key protein that stimulates cell growth, proliferation, and differentiation [1]. By binding to its receptor on cell surfaces, EGF triggers signaling pathways that regulate tissue repair and cell survival [2]. However, overproduction of EGF can drive uncontrolled cell division and promote tumor growth [1]. This gene is highly active in epithelial tissues and plays a critical role in liver regeneration [3]. Consequently, genetic variations that alter EGF levels are widely studied for their impact on cancer susceptibility and chronic tissue scarring [3] [4].
Variant Impact: The rs4444903 variant, also known as +61A>G, is located in the 5' untranslated region of the EGF gene and directly influences how much EGF protein is produced [1]. The G allele is associated with higher transcriptional activity, leading to increased levels of EGF in the body [5]. Conversely, the A allele is linked to lower serum levels of EGF [5]. Because EGF promotes cell division, the higher-producing G allele has been associated with an increased risk of several cancers, particularly liver cancer and glioma [1] [2]. In contrast, the lower-producing A allele appears to have a protective effect against these malignancies [1].
Key Insight: The G allele of this variant acts like a gas pedal for epidermal growth factor production, which can accelerate cell division and increase the risk of certain cancers, especially in the presence of chronic liver inflammation.
Location: EGF. Chromosome 4 · 4q25 · 109.9 Mb
Estimated prevalence by population
Global 26.2%; European 36.1%; African 9.3%; East Asian 9.3%; South Asian 23.9%; Americas 23.5%; Ashkenazi 27.8%; Finnish 41.9%; Middle Eastern 24.0%; Amish 26.3%.
Estimated AA genotype frequency.
Global 46.4%; European 48.0%; African 42.3%; East Asian 42.4%; South Asian 50.0%; Americas 50.0%; Ashkenazi 49.8%; Finnish 45.6%; Middle Eastern 50.0%; Amish 50.0%.
Estimated AG genotype frequency.
Global 27.4%; European 15.9%; African 48.4%; East Asian 48.2%; South Asian 26.1%; Americas 26.5%; Ashkenazi 22.3%; Finnish 12.4%; Middle Eastern 26.0%; Amish 23.7%.
Estimated GG genotype frequency.
Showing effects for A/A genotype
Cancer & Oncology
Gastrointestinal Cancers
Liver Cancer. Evidence: 4/10. Source: PMID 25927412. Typical Risk.
Gallbladder Cancer. Evidence: 3/10. Source: PMID 18571008. Typical Risk.
Brain & Nervous System Cancers
Glioma. Evidence: 4/10. Source: PMID 23645212. Typical Risk.
Organ Systems
Liver Function & Disease
Liver Fibrosis. Evidence: 3/10. Source: PMID 22122913. Typical Progression.
Showing effects for A/G genotype
Liver Cancer. Evidence: 4/10. Source: PMID 25927412. ~3.5x Higher Risk.
Glioma. Evidence: 4/10. Source: PMID 23645212. Increased Risk.
Liver Fibrosis. Evidence: 3/10. Source: PMID 22122913. Faster Progression.
Showing effects for G/G genotype
Gallbladder Cancer. Evidence: 3/10. Source: PMID 18571008. ~3x Higher Risk.
What this genotype means for the people who carry it
Sample genotype: AA (Homozygous)
An inheritance of two A alleles is associated with lower baseline levels of epidermal growth factor (EGF) in the body [1]. Because EGF is a powerful stimulator of cell growth, lower levels mean there is less biological drive for uncontrolled cell proliferation [1]. Multiple clinical studies and meta-analyses have shown that individuals with this genetic profile have a significantly lower risk of developing hepatocellular carcinoma (liver cancer) compared to G allele carriers, particularly in the context of chronic liver diseases like cirrhosis or hepatitis [2] [3]. It is also associated with a typical, non-elevated risk for gliomas (brain tumors) [4]. Furthermore, women with this profile do not experience the increased risk of gallbladder cancer seen with other genotypes [5]. Overall, this baseline represents a protective factor against EGF-driven malignancies. Maintaining a healthy lifestyle further supports these natural protective mechanisms. Regular medical checkups remain important for overall wellness, but this genetic makeup does not add extra cancer risk.
Typical EGF protein levels; Lower risk of liver cancer; Typical risk of glioma.
Sample genotype: AG (Heterozygous)
A single copy of the G allele increases the transcription of the EGF gene, leading to elevated levels of epidermal growth factor [1]. This increase in EGF can promote cell division and tissue regeneration, but it also raises the risk of malignant transformation [1]. In patients with chronic liver conditions, such as alcoholic cirrhosis or hepatitis, this genetic profile is associated with an approximately 3.5-fold higher risk of developing hepatocellular carcinoma [2] [3]. Research also indicates a moderately increased risk for gliomas, which are tumors of the brain and spinal cord [4]. However, this profile does not appear to significantly raise the risk of gallbladder cancer in females, which is primarily associated with carrying two copies of the G allele [5]. Managing lifestyle factors that affect liver health is particularly relevant for individuals with this genetic profile. Avoiding excessive alcohol consumption and maintaining a balanced diet can help minimize chronic liver inflammation. These proactive habits are beneficial for overall cellular health.
Elevated EGF protein levels; Higher risk of liver cancer with cirrhosis; Increased risk of glioma.
Sample genotype: GG (Homozygous)
A double copy of the G allele results in the highest levels of epidermal growth factor (EGF) [1]. Elevated EGF levels can accelerate cell division and tissue remodeling, which may facilitate tumor growth and progression [1]. In the presence of chronic liver stressors like hepatitis or cirrhosis, this genetic profile is associated with an approximately 3.5-fold increased risk of hepatocellular carcinoma [2] [3]. It is also linked to a higher susceptibility to gliomas, including aggressive glioblastomas [4]. Additionally, female carriers of this genotype have been found to have an approximately 3-fold higher risk of gallbladder cancer [5]. Chronic hepatitis C patients with this profile may also experience faster progression of liver fibrosis at a younger age [6]. These findings highlight the importance of monitoring and protecting liver and metabolic health. Proactive measures to support liver function, such as limiting alcohol and avoiding toxins, are highly recommended. Discussing these genetic patterns with a healthcare provider can offer personalized context.
Highest baseline EGF protein levels; Higher risk of liver cancer with cirrhosis; Increased risk of glioma; Higher gallbladder cancer risk in females.
Variants with shared genetic architecture
rs17401966 · KIF1B Gene · Chr 1 · Liver Cancer Risk
rs2596542 · MICA-AS1 Gene · Chr 6 · Liver Cancer Risk
rs55705857 · CCDC26 Gene · Chr 8 · Brain Tumor Risk
Association between epidermal growth factor gene rs4444903 polymorphism and risk of glioma.
Content updated August 2026.
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