Investigation of Differences in P53 Gene Polymorphisms between Schizophrenia and Lung Cancer Patients in the Turkish Population

Objective. The reduced incidence of cancer observed in schizophrenia patients may be related to differences in genetic background. It has been suggested that genetic predisposition towards schizophrenia is associated with reduced vulnerability to lung cancer, and p53 gene is one of the candidate genes. In our study, we aimed to investigate polymorphisms in the BstUI in exon 4 and MspI in intron 6 restriction sites of the p53 gene in Turkish schizophrenia patients, lung cancer patients, and controls. Material and Methods. Allele and genotype incidence of these polymorphisms with their haplotype combinations were studied in 100 Turkish lung cancer and schizophrenia patients and 100 controls without malignant and schizophrenia diseases. The genotype characteristics were determined by PCR-based RFLP method using DNA extracted from peripheral blood. Results. For the BstUI and MspI polymorphism, there were found significant differences in the genotype and allele frequencies between schizophrenia and lung cancer patients with control groups (P < .01). The analysis based on haplotype frequencies showed the presence of BstUI-MspI 2-1 haplotype in cancer patients (12%) in contrast to the absence of this haplotype in schizophrenia and controls. Only in lung cancer patients we found both significant decrease of A1 allele of the p53 codon 72 (OR 0.23, 95% CI 0.9–0.58) and A1/A1 homozygous genotype (P < .0001, OR 0.19). Conclusion. The results of this study suggest a protective effect of A1 allele against lung cancer, and the p53 MspI polymorphism may modify the susceptibility to lung cancer as a single factor rather than in combination with BstUI polymorphism

Serum paraoxonase and arylesterase activities in patients with lung cancer in a Turkish population

BACKGROUND: Lung cancer (LC) is the leading cause of cancer-related deaths. Oxidative DNA damage may contribute to the cancer risk. The antioxidant paraoxonase (PON1) is an endogenous free radical scavenger in the human body. The aim of this study was to determine serum PON1 and arylesterase (ARE) activities in patients with newly diagnosed LC. METHODS: This case control study involved a total of 39 patients with newly diagnosed LC (untreated) and same number of age- and sex-matched healthy individuals. Serum PON1 and ARE activities in addition to lipid parameters were measured in both groups. RESULTS: Serum PON1 and ARE activities were found to be lower in patients with LC compared to the controls (p = 0.001 and p = 0.018, respectively). The ratio of PON1/high density lipoprotein (HDL) was significantly lower in the LC group compared to the control one (p = 0.009). There were positive correlations between the serum levels of HDL and PON1 in both the control (r = 0.415, p = 0.009) and the LC groups (r = 0.496, p = 0.001), respectively. PON1 enzyme activity was calculated as three different phenotypes in both groups. In regard to lipid parameters, total cholesterol levels were significantly lower (p = 0.014) in the LC group whereas the other lipid parameters such as HDL, LDL, and triglyceride levels were not significantly different among groups. CONCLUSION: Serum PON1 activity is significantly low in the LC group compared with the healthy controls. Metastasis status and cigarette smoking do not affect serum PON1 activity in the LC patients

Prospective Observational Study of Pazopanib in Patients with Advanced Renal Cell Carcinoma (PRINCIPAL Study)

Background: Real-world data are essential to accurately assessing efficacy and toxicity of approved agents in everyday practice. PRINCIPAL, a prospective, observational study, was designed to confirm the real-world safety and efficacy of pazopanib in patients with advanced renal cell carcinoma (RCC). Subjects, Materials, and Methods: Patients with clear cell advanced/metastatic RCC and a clinical decision to initiate pazopanib treatment within 30 days of enrollment were eligible. Primary objectives included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), relative dose intensity (RDI) and its effect on treatment outcomes, change in health-related quality of life (HRQoL), and safety. We also compared characteristics and outcomes of clinical-trial-eligible (CTE) patients, defined using COMPARZ trial eligibility criteria, with those of non-clinical-trial-eligible (NCTE) patients. Secondary study objectives were to evaluate clinical efficacy, safety, and RDI in patient subgroups. Results: Six hundred fifty-seven patients were enrolled and received ≥1 dose of pazopanib. Median PFS and OS were 10.3 months (95% confidence interval [CI], 9.2–12.0) and 29.9 months (95% CI, 24.7 to not reached), respectively, and the ORR was 30.3%. HRQoL showed no or little deterioration over time. Treatment-related serious adverse events (AEs) and AEs of special interest occurred in 64 (9.7%), and 399 (60.7%) patients, respectively. More patients were classified NCTE than CTE (85.2% vs. 14.8%). Efficacy of pazopanib was similar between the two groups. Conclusion: PRINCIPAL confirms the efficacy and safety of pazopanib in patients with advanced/metastatic RCC in a real-world clinical setting. Implications for Practice: PRINCIPAL is the largest (n = 657) prospective, observational study of pazopanib in patients with advanced/metastatic renal cell carcinoma, to the authors’ knowledge. Consistent with clinical trial results that often contain specific patient types, the PRINCIPAL study demonstrated that the effectiveness and safety of pazopanib is similarly safe and effective in patients with advanced kidney cancer in a real-world clinical setting. The PRINCIPAL study showed that patients with advanced kidney cancer who are treated with first-line pazopanib generally do not show disease progression for approximately 10 months and generally survive for nearly 30 months

Sex-Specific Mediating Role of Insulin Resistance and Inflammation in the Effect of Adiposity on Blood Pressure of Prepubertal Children

Objective: To evaluate the association between obesity indices and blood pressure (BP) at 4 years of age, in each sex, and to quantify to which extent this association is mediated by inflammation and insulin resistance (IR). Materials and Methods: We studied 1250 4-year-old children selected from the population-based birth cohort Generation XXI. Associations between body mass index (BMI) z-score and waist-to-height ratio (WHtR), office BP, inflammation (high sensitivity C-reactive protein) and IR (HOMA-IR index) were assessed. Path Analysis, a modified multivariate regression approach, was applied to test causal models and quantify direct and indirect effects of predictors of systolic (SBP) and diastolic BP (DBP). Results: SBP and DBP increased significantly with BMI and WHtR in both sexes. There was a strong direct association (explaining 74.1-93.2% of the total association) of both measures of adiposity with SBP, in both sexes. This association was additionally indirectly mediated by IR, particularly regarding WHtR (20.5% in girls and 9.4% in boys). Mediation by inflammation did not reach statistical significance in either sex. Regarding DBP, the direct effect of adiposity was strong (>95% for BMI and WHtR in boys) and the mediation by IR was much smaller in boys than in girls. Discussion: The direct association between adiposity and BP in healthy 4-year-old children is strong and IR plays an important mediating role. The strength of effects of IR and inflammation suggests sex differences in the complex interplay between BP, adiposity and inflammation