Epidermal growth factor genetic variation, breast cancer risk, and waiting time to onset of disease.
Growth factors are important mediators of proliferation. Deregulation in growth factor mechanisms as well as in its receptors will contribute to cancer development. One of the most important is the epidermal growth factor (EGF), which is encoded by EGF gene. A functional polymorphism at position 61 (A/G) is associated with increased expression of EGF. Thus, we proposed to assess genotype frequencies in a case-control study and appraise their association to breast cancer risk. Using the polymerase chain reaction technique combined with restriction enzyme fragment length polymorphism (PCR-RFLP) we analyzed DNA from 883 women (500 controls and 383 breast cancer patients). Our results suggested that carriers of G homozygous genotype had a lower risk for developing breast cancer (odds ratio = 0.68; 95% confidence intervals, 0.46-1.01). Further, we showed that the waiting time for onset of breast cancer in G homozygous patients for EGF genotypes (55 years) was significantly lower in comparison to A-allele carriers (59 years) (log-rank test: p = 0.038). EGF is produced in mammary tissue and acts in the mammalian development. A lower risk for breast cancer in GG carriers might be explained through EGF receptor internalization promoted by EGF.
Araújo
Ana Paula
AP
Molecular Oncology Group, Portuguese Institute of Oncology-Porto, Porto 4200-072, Portugal.
Ribeiro
Ricardo
R
Pinto
Daniela
D
Pereira
Deolinda
D
Sousa
Berta
B
Mauricio
Joaquina
J
Lopes
Carlos
C
Medeiros
Rui
R
D002288:Adenocarcinoma, Mucinous / Q000235:genetics* / Q000556:secondary; D000328:Adult; D017668:Age of Onset; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000556:secondary; D018275:Carcinoma, Lobular / Q000235:genetics* / Q000556:secondary; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000556:secondary; D016022:Case-Control Studies; D004815:Epidermal Growth Factor / Q000235:genetics*; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis
D004815:Epidermal Growth Factor; D066246:ErbB Receptors