Association of a genetic variant in Interleukin-10 gene with increased risk and inflammation associated with cervical cancer.

BACKGROUND: Cervical-cancer is among the most commonly diagnosed cancers in women, and infection with human papillomavirus (HPV) is associated with an increased risk of cervical cancer and altered serum concentrations of inflammatory cytokines. We have explored the association between a genetic variation in the Interleukin-10 (IL-10) gene (rs1800896) and cervical cancer risk and its relationship with tissue Interferon gamma (IFN-γ), Transforming growth factor beta (TGF-ß), Tumor necrosis factor alpha (TNF-α) concentrations in women with cervical cancer. METHODS: A total of 315 women with, or without cervical cancer, were recruited into the study. DNA was extracted from cervical cells, and genotyping was undertaken using Taq-man real-time PCR. The genotype frequency and allele distribution were analyzed together with their association with pathological data. The association of the rs1800896 gene variation with tissue levels of the inflammatory cytokines was also investigated. RESULTS: Our data showed a significant association between the A allele of the rs1800896 gene variant and the presence of cervical cancer. In particular, patients with AG/AA genotypes had an increased risk of cervical cancer with an odds ratio of 1.929 (95% confidence interval [CI]: 0.879-4.23, P < 0.001) in a recessive model, compared with the GG genotype. Also, the tissue concentrations of IFN-γ, TGF-ß, and TNF-α in cervical tissues were significantly higher in women with cervical cancer (P < 0.001) and were associated with the AA genotype. CONCLUSION: We have found an association between the polymorphism rs1800896 in the IL-10 gene and an increased risk of cervical cancer as well as a higher level of tissue inflammatory cytokines. Further investigations are necessary on the value of emerging biomarkers for the risk stratification for the management of cervical cancer patients.

The interaction of high and low-risk human papillomavirus genotypes increases the risk of developing genital warts: A population-based cohort study.

Cervical cancer is among the most common type of cancers in women and is associated with human papillomavirus (HPV) infection. Genital warts are also reported to be linked with HPV infection types 11 and 6. In turn, clinical characteristics and morphological features of warts may be useful in the prediction of prognosis and in making treatment decisions. Thus, we have investigated the association of high and low-risk HPVs genotype with genital wart risk, as well as pathological and cytological information in cases recruited from a population-based cohort study of 1380 patients. Patients infected with HPV genotype 6 or 11 had an increased risk of having warts, with OR of 2.34 (95% CI: 0.955-5.737, P = 0.06). Also, this association was enhanced in the presence of high plus low-risk HPV for having genital wart (OR: 2.814; 95%: 1.208-6.55, P = 0.017) and cases having high-risk HPV (OR: 2.329; 95% CI: 1.029-5.269, P = 0.042). Moreover, we observed patients with genital warts having CIN2/3, indicating the importance of informing the physician to the patient to prevent more severe lesions. Our data demonstrated that patients with both low/high-risk HPV types had an increased risk of developing genital warts and persistent infection with HPV was a necessary precursor for the increase in cervical lesions.

Reactive oxygen species in colorectal cancer: The therapeutic impact and its potential roles in tumor progression via perturbation of cellular and physiological dysregulated pathways.

Reactive oxygen species (ROS) are produced by mitochondria during metabolism. In physiological states, the production of ROS and their elimination by antioxidants are kept in balance. However, in pathological states, elevated levels of ROS interact with susceptible cellular target compounds including lipids, proteins, and DNA and deregulate oncogenic signaling pathways that are involved in colorectal cancer (CRC) carcinogenesis. Although antioxidant compounds have been successfully used in the treatment of CRC as prevention approaches, they have also been shown in some cases to promote disease progression. In this review, we focus on the role of ROS in gastrointestinal homeostasis, CRC progression, diagnosis, and therapy with particular emphasis on ROS-stimulated pathways.

Association of dysglycemia with mortality in children receiving parenteral nutrition in pediatric intensive care unit.

Khajavi L, Khademi G, Mehramiz M, Norouzy A, Safarian M. Association of dysglycemia with mortality in children receiving parenteral nutrition in pediatric intensive care unit. Turk J Pediatr 2018; 60: 134-141. One of the most important complications of parenteral nutrition (PN) is a high incidence of hyperglycemia. The aim of this study was to assess the effect of parenteral nutrition dysglycemia on clinical outcomes among critically ill children in pediatric intensive care unit (PICU). Charts of 201 critically ill children admitted in PICU during 2012-2015 were reviewed retrospectively. We included patients who were < 6 years of age and had received at least 60% of total energy from PN for a minimum of 5 days in PICU. The exclusion criteria were patients with diagnosis of diabetes mellitus, primary hypoglycemia, inborn errors of metabolism and patients who received dialyses. We defined hyperglycemia as blood glucose ≥150 mg/dl, and hypoglycemia as blood glucose ≤60 mg/dl. Based on blood glucose, patients were divided into four groups: `only hyperglycemia group` (having at least one hyperglycemia episode), `only hypoglycemia group` (having at least one hypoglycemia episode), `glucose variability` (having both hypoglycemia and hyperglycemia episodes), and `normoglycemia` (all glucose measurements were in normal range). Hyperglycemia and hypoglycemia occurred in 52.8% and 24.9% of all children, respectively; glucose variability occurred in 13.9% of all children. Multiple logistic regression analysis showed that glucose variability (OR: 3.1; 95% CI: 1.13-8.43) and hyperglycemia (OR: 2.14; 95% CI: 1.1-4.57) were associated with mortality independently. In `only hypoglycemia` group (N=22) there were only three deaths. There were no significant differences in the quantities of macronutrients prescribed via parenteral nutrition among the four blood glucose groups. Results of this study showed that hyperglycemia and glucose variability are strong predictors of mortality in pediatrics receiving parenteral nutrition.

A genetic variant in CDKN2A/B gene is associated with the increased risk of breast cancer.

BACKGROUND: Breast cancer is among the leading cause of cancer-related-deaths in women, supporting the need for the identification of novel prognostic and predictive biomarkers. Recent studies have identified common genetic variants in a region on chromosome 9p21 associated with an increased risk of developing different cancers. Here, we explored the association of a genetic variant in CDKN2A/B, rs10811661, for the first time in 564 subjects with/without breast cancer. METHOD: Genotyping was performed using TaqMan real time PCR method. The associations of this genetic variant with breast cancer risk and pathological information of patients were assessed. RESULTS: We observed that patients with breast cancer had a higher frequency of TT genotype (P<.001) than control group, which was associated with advanced TNM classification (P=.04) and larger tumor size (P=.014), as detected by the recessive genetic inheritance model. Moreover, the logistic regression under recessive genetic model revealed that breast cancer patients with TT had higher risk of breast cancer, compared to CC/CT genotypes (eg, OR=4.9, 95% CI:1.9-12, P=.001), after adjusted for potential confounders, age, BMI, and family history. CONCLUSION: We demonstrated that patients carrying the TT genotype for CDKN2A/B rs10811661 polymorphism had the increased risk of breast cancer susceptibility. However, further investigations are warranted in a larger and prospective setting to explore the value of this marker as a risk stratification marker in breast cancer.

Adherence to a Dash-style diet in relation to depression and aggression in adolescent girls.

The aim of this study was to assess adherence to the Dietary Approach to Stop Hypertension (DASH) dietary pattern in relation to depression and aggression in adolescent girls. The study was carried out among 580 girls aged between 12 and 18 years of age. DASH scores were determined according to the method of Fung et al. A Persian version of the Beck Depression Inventory and Buss-Perry questionnaire were used for the assessment of depression and aggression. We analysed our data using crude and adjusted models. Adjustments were made for age, energy intake, mother's job status, passive smoking, start of menstruation, parental death, parental divorce, physical activity level and body mass index, using three different models. A high adherence to a Dash-style diet (for individuals in the upper quartile) was associated with a lower odds of depression compared with subjects with lower adherence (those in the lowest quartile) (OR 0.47; 95% CI 0.26-0.84, P-value = 0.009); these associations remained significant after adjustments. However, we did not obtain any significant relationship between a DASH-style diet and aggression. We observed a significant inverse relationship between greater adherence to a DASH diet and lower odds of depression. Further prospective studies are needed to confirm these findings.

Serum high C reactive protein concentrations are related to the intake of dietary macronutrients and fiber: Findings from a large representative Persian population sample.

OBJECTIVE: Serum high-sensitivity CRP is a marker of inflammation and an independent predictor of chronic diseases. However, the effect of diet on serum hs-CRP is unclear. The aim of this study was to investigate the relationship between dietary macronutrient intake and serum hs-CRP. DESIGN AND METHODS: We recruited 9778 adults, aged 35-65years as part of the MASHAD study. Dietary intake was determined using 24-hour dietary recall and several biochemical parameters including serum hs-CRP were measured. Analysis of covariance was used for assessment of crude and energy-adjusted nutrients across quartiles of serum hs-CRP. To find the association of dietary nutrients intake and serum hs-CRP level, we used logistic regression in different model. RESULTS: Unadjusted and adjusted multivariate analyses indicate that there was a significant positive association between dietary protein and sodium intake and serum hs-CRP concentrations. There was also a positive association with dietary fat and cholesterol and serum hs-CRP in the adjusted models. There was a significant inverse association between dietary carbohydrate and fiber consumption and serum hs-CRP in both crude and adjusted models. CONCLUSION: We have found a significant positive association between the dietary intake of fat, protein, cholesterol and sodium and hs-CRP level, and an inverse correlation between dietary carbohydrate and fiber and serum hs-CRP in a large representative Iranian population.

Association of a Vascular Endothelial Growth Factor genetic variant with Serum VEGF level in subjects with Metabolic Syndrome.

BACKGROUND: The metabolic syndrome (MetS) is a clustering of metabolic disorders that is associated with an increased risk of developing cardiovascular-disease, diabetes, and related diseases. Against this background, Vascular Endothelial Growth Factor (VEGF) plays an essential role in angiogenesis, vascular permeability, and hematopoiesis and its increased level is reported to be associated with increasing the risk of developing cardiovascular-disease, stroke and diabetes. Therefore the aim of present study was to explore the association of serum VEGF level and its associated genetic-polymorphism, rs10738760 (A>G) at 9p24.2, in 850 subjects with/without MetS. METHODS: MetS was defined according to the International-Diabetes-Federation criteria. Genotyping was carried out using Polymerase chain reaction-amplification refractory mutation system. Anthropometric/biochemical parameters, including FBG, Triglyceride, HDL, TC, etc., were determined followed by univariate and multivariate analyses. RESULTS: MetS patients had significantly higher levels of BMI, waist-circumference, cholesterol, triglyceride, Hs-CRP and SBP/DBP, while the HDL-C levels was lower in patients group, compared to control group (P<0.05). Moreover, our analysis showed that MetS patients with GA or AA genotypes had a significantly (P=0.03) higher serum level of VEGF. CONCLUSIONS: we demonstrate an association between a VEGF genetic variant with MetS, suggesting its role as a risk stratification factor for MetS.