rs4444903 is a SNP, also known as +61, located in the promoter region of the epidermal growth factor EGF gene that influences the amount of EGF produced. The rs4444903(G) allele appears to produce higher amounts of EGF than the (A) allele.
A study of 2 Caucasian populations of patients with alcoholic cirrhosis indicates that, for these patients, the presence of the risk allele rs4444903(G) increases the chances of developing hepatocellular carcinoma (liver cancer). After adjusting for age, sex, race, etiology, and severity of cirrhosis the number of (G) copies led to an odds ratio for either (G;G) or (A;G) genotypes versus the (A;A) genotype of 3.49 (CI: 1.29-9.44, p=.01). [PMID 18167406]
In another study, analysis of 197 glioma patients showed that the rs4444903(G) allele conferred higher risks for gliomas (odds ratio 1.32, CI: 1.04-1.67), glioblastomas (OR, 1.47, CI: 1.02-2.10), and oligodendrogliomas (OR, 1.55, CI: 1.07-2.23). In general, the risk was about the same for a carrier or one or two (G) alleles, however, no significant association was observed with patients' overall survival.[PMID 17473192]
A study of 126 Indian gallbladder cancer patients concluded that the rs4444903(G;G) genotype was at increased risk, but only in females (odds ratio 3.45, CI: 1.52-7.82, p = 0.003).[PMID 18571008]
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[PMID 19010984] rs4444903, rs2298991, rs7692976 and rs4533485 significantly interacted with gender for acute respiratory distress syndrome risk.
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[PMID 20487573] Association between EGF +61 G/A and glioma risk in a Chinese population
[PMID 19319135] Common genetic variability in ESR1 and EGF in relation to endometrial cancer risk and survival.
[PMID 21567271] Effect of rs6983267 polymorphism in the 8q24 region and rs4444903 polymorphism in EGF gene on the risk of sporadic colorectal cancer in Iranian population
[PMID 22122913] Association between the epidermal growth factor rs4444903 G/G genotype and advanced fibrosis at a young age in chronic hepatitis C
[PMID 22829952] A Functional +61G/A Polymorphism in Epidermal Growth Factor Is Associated with Glioma Risk among Asians
[PMID 15663953] Epidermal growth factor gene polymorphism is different between schizophrenia and lung cancer patients in Korean population.
[PMID 17204151] VEGF, FGF1, FGF2 and EGF gene polymorphisms and psoriatic arthritis.
[PMID 18676680] Pathway-based evaluation of 380 candidate genes and lung cancer susceptibility suggests the importance of the cell cycle pathway.
[PMID 19372140] EGFR pathway polymorphisms and bladder cancer susceptibility and prognosis.
[PMID 19379518] Development of a fingerprinting panel using medically relevant polymorphisms.
[PMID 19822020] Genetic factors associated with intestinal metaplasia in a high risk Singapore-Chinese population: a cohort study.
[PMID 20203692] A functional epidermal growth factor (EGF) polymorphism, EGF serum levels and renal cell carcinoma risk in a Chinese population.
[PMID 21440548] A functional polymorphism in the epidermal growth factor gene is associated with risk for hepatocellular carcinoma.
[PMID 22236006] Carriage of the EGF rs4444903 A>G functional polymorphism associates with disease progression in chronic HBV infection.
[PMID 23403233] EGF +61A>G polymorphism and gastrointestinal cancer risk: A HuGE review and meta-analysis
[PMID 24363559] A functional polymorphism in the epidermal growth factor gene predicts hepatocellular carcinoma risk in Japanese hepatitis C patients
[PMID 22848662] Polymorphisms on 8q24 are associated with lung cancer risk and survival in Han Chinese.
[PMID 23201894] Lack of association between EGF +61A>G polymorphism and melanoma susceptibility in Caucasians: a HuGE review and meta-analysis.
[PMID 23645212] Association between epidermal growth factor gene rs4444903 polymorphism and risk of glioma.
[PMID 23790025] Association of epidermal growth factor and epidermal growth factor receptor polymorphisms with the risk of hepatitis B virus-related hepatocellular carcinoma in the population of North China.
[PMID 24754849] Polymorphism in the epidermal growth factor gene is associated with pre-eclampsia and low birthweight
[PMID 24834259] The effect of 5'untranslated region polymorphism in EGF gene, rs4444903, on colorectal cancer
[PMID 24558090] Genetic markers of bevacizumab-induced hypertension
[PMID 25927412] Association between epidermal growth factor gene +61A/G polymorphism and the risk of hepatocellular carcinoma: a meta-analysis based on 16 studies