The EGF 61A/G polymorphism - a predictive marker for recurrence of liver metastases from colorectal cancer.
BACKGROUND
Epidermal growth factor (EGF) plays an important role in tumorigenesis. Variations in the DNA sequence of the gene EGF can lead to alterations in EGF activity, which is suspected to influence tumor progression. This retrospective study aimed to investigate the influence of EGF 61A/G polymorphism on the recurrence of liver metastases after hepatic surgery in patients with colorectal cancer.


METHODS
EGF 61A/G polymorphism was determined in 268 consecutive patients (175 [65%] men and 93 [35%] women, mean age 62 +/- 10.3 years) who had liver metastases at primary diagnosis and were treated by surgery with curative intent (R0) for liver metastases from colorectal cancer.


RESULTS
Overall, 81 of 268 (30%) patients exhibited wild-type EGF 61 A/A, 137 (51%) were heterozygous EGF 61 A/G and 50 (19%) were homozygous EGF 61 G/G. After adjusting for age, sex, UICC stage and tumor location, we observed a trend-wise 1.6-fold increased risk for hepatic recurrence (HR 1.6; 95% CI 1.0-2.5, P = 0.06) in individuals with the G/G genotype compared with carriers of the A-allele. The effect was much more pronounced in younger patients (<or= 65 years), who showed a 2.0-fold increased risk of hepatic recurrence (HR 2.0; 95% CI 1.1-3.5, P = 0.021). No effect was observed in older patients (>or= 65 years). Interestingly, male patients with EGF G/G had a 1.6-fold higher risk of recurrence (HR 1.6; 95% CI 1.0-2.5, P = 0.07). A significant correlation (P = 0.033) was detected between Dukes classification and the homozygous 61 G/G genotype.


CONCLUSIONS
Despite the limitations of our study, the retrospective results indicate that carriers of the EGF polymorphism might be at higher risk of developing liver recurrences. If confirmed in subsequent studies, genotyping for the EGF A/G variant might help in identification of patients at high risk of recurrence of liver metastases.
Kovar
Florian M
FM
Department of Medical and Chemical Laboratory Diagnostics, Medical University Vienna, Vienna, Austria.
Thallinger
Christiane
C
Marsik
Claudia L
CL
Perkmann
Thomas
T
Puhalla
Harald
H
Haslacher
Helmuth
H
Wrba
Fritz
F
Wagner
Oswald F
OF
Gruenberger
Thomas
T
Endler
Georg
G
D001317:Austria / Q000453:epidemiology; D014408:Biomarkers, Tumor / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D004815:Epidermal Growth Factor / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D008113:Liver Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015203:Reproducibility of Results; D018570:Risk Assessment / Q000379:methods; D012680:Sensitivity and Specificity
D014408:Biomarkers, Tumor; D004815:Epidermal Growth Factor