The relationship between the epidermal growth factor (EGF) 5'UTR variant A61G and melanoma/nevus susceptibility.
The inheritance of a G allele in position 61 in the 5'UTR of the epidermal growth factor (EGF) gene has been reported to increase melanoma susceptibility, a finding we have investigated in this study. The most potent phenotypic risk factor for melanoma is the atypical mole syndrome (AMS) phenotype. Our hypothesis is that the AMS is genetically determined and that nevus genes are also low penetrance melanoma susceptibility genes. We report that the G allele frequencies were the same in 697 healthy women and 380 melanoma cases (OR 0.97, 95% CI 0.8-1.2 p=0.76). We therefore found no evidence that this polymorphism is a melanoma susceptibility gene. Furthermore, we found no evidence that the polymorphism controls the nevus phenotype (nevus number, number atypical nevi or AMS phenotype). We did find some evidence that the G allele may be associated with decreased tumor Breslow thickness (OR 0.5, 95% CI 0.3-0.9) for the A/A genotype versus A/G and G/G combined in tumors of thickness >3.5 vs < or =3.5 mm and may therefore act as a predictor of survival, although this finding is not in accord with the original report. This is the second study to find no association between EGF +61 and melanoma susceptibility.
Randerson-Moor
J A
JA
Genetic Epidemiology Division, Cancer Research UK, Cancer Genetics Building, St James's University Hospital, Leeds, UK.
Gaut
R
R
Turner
F
F
Whitaker
L
L
Barrett
J H
JH
Silva
I dos Santos
Idos S
Swerdlow
A
A
Bishop
D T
DT
Bishop
J A Newton
JA
D020121:5' Untranslated Regions / Q000235:genetics; D000328:Adult; D016022:Case-Control Studies; D004815:Epidermal Growth Factor / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics*; D008875:Middle Aged; D009506:Nevus / Q000235:genetics*; D019683:Penetrance; D011110:Polymorphism, Genetic; D012878:Skin Neoplasms / Q000235:genetics*
D020121:5' Untranslated Regions; D004815:Epidermal Growth Factor