Vascular Endothelial Growth Factor (VEGF) Polymorphisms and Serum VEGF Levels in Women With Epithelial Ovarian Cancer, Benign Tumors, and Healthy Ovaries.

OBJECTIVE: This study analyzed the relation of 5 single-nucleotide polymorphisms (SNPs) in the VEGF (vascular endothelial growth factor) gene in patients with epithelial ovarian cancer (EOC), compared with patients carrying benign tumors or healthy ovaries. We studied serum VEGF levels and the relation with SNPs and association between VEGF SNPs and haplotypes with progression-free survival (PFS) in patients with cancer. METHODS: The genotyping of VEGF gene polymorphisms (-2578 C/A, -1154 G/A, -460 T/C, +405 G/C, +936 C/T) was performed in DNA isolated from blood samples of 100 women. The different genotypes were evaluated by quantitative real-time polymerase chain reaction. Vascular endothelial growth factor protein concentration was assessed in serum using solid-phase sandwich enzyme-linked immunosorbent assay. RESULTS: We found statistically significant differences in the distribution of VEGF genotypes among the 3 groups of patients: -2578 C/A between those with EOC and healthy ovary (P = 0.04), -460 T/C between those with EOC and healthy ovary (P = 0.03), and -460 T/C between those with benign tumors and healthy ovary (P = 0.02). Vascular endothelial growth factor serum levels were analyzed in patients with EOC. Higher levels were found in patients with clear cell carcinoma compared with those with serous, mucinous, or endometrioid tumors (P < 0.05). No clear association was observed between VEGF SNPs and serum VEGF levels. There was no significant correlation between VEGF SNPs and PFS. In haplotype analysis, CGTCT and CGTGT showed worse prognosis without reaching the statistical significance. CGCGC and AGTGC haplotypes had statistically significant differences among patients with EOC, benign tumors, and healthy ovaries (Ps = 0.046 and 0.041, respectively). CONCLUSIONS: The distribution of VEGF genotypes was different in patients with EOC, compared with those with benign tumors or women with healthy ovaries. Vascular endothelial growth factor serum levels were higher in patients with clear cell carcinoma. No correlation was found with improved PFS, but CGTCT and CGTGT haplotypes showed worse prognosis.

ARMS2 A69S polymorphism is associated with the number of ranibizumab injections needed for exudative age-related macular degeneration in a pro re nata regimen during 4 years of follow-up.

PURPOSE: To investigate whether single-nucleotide polymorphisms (SNPs) known to be strongly associated with the development of age-related macular degeneration (AMD) have an influence on recurrence rate of choroidal neovascularization (CNV) activity during 4-year ranibizumab treatment for exudative AMD. METHODS: This prospective study included 103 treatment-naïve patients (103 eyes) that received initially a loading dose of 3 monthly ranibizumab injections and thereafter, were treated according to an as-needed regimen for a 4-year follow-up period. Baseline values, visual outcome, and recurrence rate were examined. CFH Y402H and ARMS2 A69S polymorphisms were determined and their association with lesion recurrence and visual outcome was analyzed using a one-way analysis of variance (ANOVA) with post hoc comparison tested by Fisher's LSD method. Multivariate linear regression analysis was then used to identify factors associated with recurrence rate. RESULTS: The cumulative total mean number of ranibizumab injections at the end of each year of the follow-up was 5.3 ± 1.8, 9.2 ± 2.9, 12.6 ± 4.6, and 15.7 ± 6.1. There was great inter-patient variability. Nineteen eyes (18.5%) did not experience recurrence during the first year, and five (4.8%) still displayed inactive CNV after 4 years of follow-up. No significant association was found between the number of injections and mean best corrected visual acuity (BCVA) change or final BCVA at the end of the study period. Genotypes had no influence on baseline characteristics or visual outcome but a significant association was found between the A69S polymorphism and the number of injections needed by the patients. Homozygous for the T risk allele required more retreatments over the 48-month follow-up. CONCLUSIONS: The ARMS2 A69S polymorphism was associated with CNV recurrence rate in our patient cohort. Prediction of a greater risk of recurrence could help to design more appropriate follow-up treatment strategies for patients with neovascular AMD.

p16 gene methylation in colorectal cancer patients with long-term follow-up.

INTRODUCTION: p16 gene plays an important role in the cell cycle regulation and is considered an important tumor suppressor gene. Several mechanisms of gene inactivation have been described; in this study we have focused on p16 gene promoter methylation. In colorectal cancer p16 gene methylation is a frequent event. METHODS: 326 patients with sporadic colorectal cancer were included. DNA was extracted from tumor tissue samples obtained during the surgical procedure. Promoter methylation was analyzed using bisulfite modification and was detected by quantitative methylation-specific PCR. Frequency of p16 methylation was analyzed and compared with other clinicopathological variables. RESULTS: p16 gene methylation was detected in 24.8% of patients. Methylation was associated with differentiation grade and with tumor location: methylation was frequent in poorly differentiated tumors and had low frequency in distal colon. The p16 promoter methylation discriminated a subgroup of patients with better prognosis in poorly differentiated tumors. CONCLUSIONS: p16 methylation was a frequent event in our population and was able to induce differences in the overall survival of patients with poorly differentiated tumors.