Analysis of EGF 61A > G polymorphism and EGF serum levels in Brazilian glioma patients treated with perillyl alcohol-based therapy

作者：Abreu da Silveira, Francisco das Chagas; Lopes, Bruno de Almeida; da Fonseca, Clovis Orlando; Quirico Santos, Thereza; Nunes de Palmer Paixao, Izabel Christina; da Fonte de Amorim, Lidia Maria

来源：Journal of Cancer Research and Clinical Oncology, 2012, 138(8): 1347-1354.

DOI：10.1007/s00432-012-1203-5

• Glioma
• Perillyl alcohol
• EGF
• Polymorphism
• PCR-RFLP

Malignant gliomas are associated with alteration in EGF/EGFR signaling. Functional EGF 61A > G polymorphism is implicated with risk, recurrence, and progression of glioma. This study aimed to establish a putative association of EGF 61A > G with risk of glioma development, production of angiogenic growth factor EGF, and the response to perillyl alcohol administered by intranasal route.
The study included 83 patients with recurrent glioma enrolled in Phase I/II trial for intranasal perillyl alcohol therapy and subjects without cancer (n = 196) as control group. DNA was extracted from blood samples, EGF genotype performed with PCR-RFLP assay, and EGF circulating levels by enzyme immunoassay. Adequate statistical tests were performed to verify associations between polymorphism and glioma risk, and genotype correlation with EGF circulating levels. The log-rank test was also used to evaluate differences on patient survival.
Patients with primary glioblastoma had high frequency of AA genotype (p = 0.037) and A allele (p = 0.037). Increased EGF circulating levels were observed in glioma patients with AA (p = 0.042), AG (p = 0.006), and AA AG (p = 0.008) genotypes compared with GG. Patients with GG genotype showed increased but not significant (p > 0.05) survival rate, and EGF levels lower than 250 pg/mL was consistently (p = 0.0374) associated with increased survival.
Presence of EGF 61A > G polymorphism in Brazilian subjects was associated with glioma risk and increased circulating EGF levels. Better response to perillyl alcohol-based therapy was observed in a group of adult Brazilian subjects with lower EGF levels.

• 出版日期2012-8