Vascular Endothelial Growth Factor (vegf) Polymorphism And Increased Risk Of Epithelial Ovarian Cancer

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Angiogenesis (AG) is essential for epithelial ovarian cancer (EOC) development. Vascular endothelial growth factor (VEGF), encoded by the VEGF gene, and endostatin, the product of the COL18A1 gene, act as a potent promoter and an inhibitor of AG, respectively. In the present study, we tested whether VEGF C936T and COL18A1 D104N polymorphisms alter the risk of EOC. Genomic DNA from 131 EOC patients and 137 controls were analyzed by polymerase chain reaction and restriction fragment length polymorphism methods. The differences between groups were analyzed by chi (2) or Fisher's exact test and logistic regression analysis. The frequency of the VEGF 936CC genotype was higher in patients than in controls (84.8 % vs. 75.3 %, P = 0.03). Individuals with respective genotypes had a 1.98 (95 % CI 1.04-3.78)-fold increased risk of EOC than those with the remaining genotypes. An excess of VEGF 936CC plus COL18A1 DN genotype was seen in patients when compared to controls (48.6 % vs. 30.5 %); however, only a tendency toward a statistically significant difference in genotype frequencies was found in the study (P = 0.06), reflecting a trend toward an increased risk of 2.44 for EOC in carriers of the combined genotype. Our data present, for the first time, preliminary evidence that VEGF C936T alone or combined with the COL18A1 D104N polymorphism of AG constitutes an important inherited EOC determinant.14116973Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Polymorphisms in apoptosis-related genes in cutaneous melanoma prognosis: sex disparity

Cutaneous melanoma (CM) cells are resistant to apoptosis, and steroid hormones are involved in this process through regulation of TP53, MDM2, BAX, and BCL2 expression. We analyzed herein sex differences in outcomes of CM patients associated with TP53 c.215G>C, MDM2 c.309T>G, BAX c.-248G>A, and BCL2 c.-717C>A polymorphisms. DNA from 121 men and 116 women patients was analyzed by polymerase chain reaction and enzymatic digestion assays. At 60 months of follow-up, shorter progression-free survival (PFS) was seen in males with MDM2 GG + BCL2 AA (20.0 vs. 62.6%, P = 0.0008) genotype. Men carriers of the genotype had poor PFS (HR 3.78, 95% CI 1.30-11.0) than others. For women, shorter PFS was associated with TP53 GC or CC (61.4 vs. 80.8%, P = 0.01) and TP53 GC or CC + MDM2 TG or GG (59.1 vs. 85.4%, P = 0.01) genotypes at the same time. Women carriers of the genotypes had poor PFS (HR 2.46, 95% CI 1.19-5.09; HR 9.49, 95% CI 1.14-78.50) than others, respectively. Our data present, for the first time, preliminary evidence that inherited abnormalities on TP53, MDM2 and BCL2 genes, enrolled in apoptosis pathways, have a pivotal role in differences of outcomes in women and men with CM342FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP2009/12602-0; 2010/18904-

Influence of functional variants Asp312Asn and Lys751Gln of Xeroderma Pigmentosum Group D (XPD) and Glutathione S-transferase Mu 1 (GSTM1) and Theta 1 (GSTT1) genes on cutaneous melanoma susceptibility and prognosis

We aimed to evaluate whether variants in repair (XPD Asp312Asn, XPD Lys751Gln) and detoxification (GSTM1, GSTT1) genes alter risk, clinicopathological aspects and survival of cutaneous melanoma (CM). Genotyping was performed in 229 CM patients and 258 controls. Individuals with XPD 312Asp/Asn or Asn/Asn plus GSTT1 null genotype were under 2.00 (95% CI: 1.06-3.79), and XPD 312Asn/Gln haplotype was under 1.44-fold (95% CI: 0.99-2.08) increased risks to CM than others. Individuals with GSTM1 plus GSTT1 null genotype had 9.61-fold (95% CI: 2.28-40.38) increased risk of metastatic CM. At 60 months of follow-up, patients with XPD 751Gln/Gln plus GSTT1 null and GSTM1 null plus GSTT1 null genotype presented 7.36 and 3.05 more chances of evolving to death in multivariate Cox analysis, respectively. In conclusion, our data indicate, for the first time, that specific variant combinations of XPD, GSTM1 and GSTT1 may increase susceptibility to CM and influence patients' clinicopathological features and survival.285631635FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP2009/12602-

CASP9 c.-1339A > G and CASP3 c.-1191A > G polymorphisms alter susceptibility and clinical aspects of head and neck squamous cell carcinoma

Single nucleotide polymorphisms (SNPs) in genes that act in intrinsic apoptosis pathway may modulate cancer susceptibility. This study investigated the roles of CASP9 c.-1339A>G (rs4645978) and CASP3 c.-1191A>G (rs12108497) SNPs on risk and behavior of head and neck (HN) squamous cell carcinoma (SCC). Methods DNA of 350 patients with HNSCC and 350 controls was analyzed by polymerase chain reaction method for genotyping. Results CASP3 c.-1191AG or GG genotype was more common in patients with HNSCC and oral cavity or oropharynx SCC than in controls; carriers of this genotype were under 2.15 and 2.81-fold increased risks of the respective tumors. CASP9 c.-1339AG or GG plus CASP3 c.-1191AG or GG genotypes were associated with oral cavity or oropharynx SCC early onset. Conclusion These findings present, for the first time, preliminary evidence that inherited abnormalities related to CASP9 c.-1339A>G and CASP3 c.-1191A>G SNPs are determinants of HNSCC risk and clinical aspects.41826652670CNPQ - Conselho Nacional de Desenvolvimento Científico e TecnológicoFAPESP – Fundação de Amparo à Pesquisa Do Estado De São Paulo401262/2013‐82012/01807‐

Association between polymorphisms in genes related to DNA base-excision repair with risk and prognosis of oropharyngeal squamous cell carcinoma

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)We examined the influence of OGG1 c.977C > G (rs1052133), APEX1 c.444T > G (rs1130409), XRCC1 c.-77T > C (rs3213245), c.580C > T (rs1799782), c.839G > A (rs25489) and c.1196G > A (rs25487) single-nucleotide polymorphisms (SNPs), involved in base-excision repair (BER) pathway, on oropharyngeal squamous cell carcinoma (OPSCC) risk and prognosis. Aiming to identify the genotypes, DNA from 200 consecutive OPSCC patients and 200 controls was analyzed by PCR-RFLP. The prognostic impact of genotypes of SNPs on progression-free survival (PFS) and overall survival of OPSCC patients was examined using the Kaplan-Meier estimates and Cox regression analyses. XRCC1 c.580CT or TT genotypes (19.5 vs. 11.0 %, P = 0.04) and XRCC1 TTGG haplotype from c.-77T > C, c.580C > T, c.839G > A and c.1196G > A SNPs (17.5 vs. 10.0 %, P = 0.04) were more common in patients with OPSCC than in controls. Carriers of combined genotypes of c.580C > T and TTGG haplotype of XRCC1 gene were under 3.35- and 3.22-fold increased risk of OPSCC than others. For survival analysis, we selected only patients with tumor at stage IV. The median follow-up time was 24.5 months. At 24 months of follow-up, PFS was shorter in patients with OGG1 c.977CC genotype when compared with others genotypes (35.5 vs. 52.1 %, log-rank test, P = 0.03). After multivariate Cox analysis, patients with OGG1 c.977CC genotype had more chance to present tumor progression when compared with others (HR 1.68, P = 0.02). Our data present, for the first time, evidence that inherited OGG1 c.977C > G; XRCC1 c.-77T > C, c.580C > T, c.839G > A and c.1196G > A abnormalities of DNA BER pathway are important determinants of OPSCC and predictors of patient outcomes.We examined the influence of OGG1 c.977C > G (rs1052133), APEX1 c.444T > G (rs1130409), XRCC1 c.-77T > C (rs3213245), c.580C > T (rs1799782), c.839G > A (rs25489) and c.1196G > A (rs25487) single-nucleotide polymorphisms (SNPs), involved in base-excision142919171926FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)2012/18623-

Comparison of enzalutamide versus abiraterone in castration-resistant prostate cancer before docetaxel: results of a propensity score-matched analysis

Sem informação3715Annual Meeting of the American Society of Clinical Oncolog