Low human papillomavirus prevalence in head and neck cancer: results from two large case-control studies in high-incidence regions

Background Recent studies support an important role for human papillomavirus (HPV) in a subgroup of head and neck squamous cell carcinomas (HNSCC). We have evaluated the HPV deoxyribonucleic acid (DNA) prevalence as well as the association between serological response to HPV infection and HNSCC in two distinct populations from Central Europe (CE) and Latin America (LA). Methods Cases (n = 2214) and controls (n = 3319) were recruited from 1998 to 2003, using a similar protocol including questionnaire and blood sample collection. Tumour DNA from 196 fresh tissue biopsies was analysed for multiple HPV types followed by an HPV type-specific polymerase chain reaction (PCR) protocol towards the E7 gene from HPV 16. Using multiplex serology, serum samples were analysed for antibodies to 17 HPV types. Statistical analysis included the estimation of adjusted odds ratios (ORs) and the respective 95% confidence intervals (CIs). Results HPV16 E7 DNA prevalence among cases was 3.1% (6/196), including 4.4% in the oropharynx (3/68), 3.8% in the hypopharynx/larynx (3/78) and 0% among 50 cases of oral cavity carcinomas. Positivity for both HPV16 E6 and E7 antibodies was associated with a very high risk of oropharyngeal cancer (OR = 179, 95% CI 35.8-899) and hypopharyngeal/laryngeal cancer (OR = 14.9, 95% CI 2.92-76.1). Conclusions A very low prevalence of HPV DNA and serum antibodies was observed among cases in both CE and LA. The proportion of head and neck cancer caused by HPV may vary substantially between different geographical regions and studies that are designed to evaluate the impact of HPV vaccination on HNSCC need to consider this heterogeneity.

Childhood Trauma and Children`s Emerging Psychotic Symptoms: A Genetically Sensitive Longitudinal Cohort Study

Objective: Using longitudinal and prospective measures of trauma during childhood, the authors assessed the risk of developing psychotic symptoms associated with maltreatment, bullying, and accidents in a nationally representative U. K. cohort of young twins. Method: Data were from the Environmental Risk Longitudinal Twin Study, which follows 2,232 twin children and their families. Mothers were interviewed during home visits when children were ages 5, 7, 10, and 12 on whether the children had experienced maltreatment by an adult, bullying by peers, or involvement in an accident. At age 12, children were asked about bullying experiences and psychotic symptoms. Children`s reports of psychotic symptoms were verified by clinicians. Results: Children who experienced maltreatment by an adult (relative risk=3.16, 95% CI=1.92-5.19) or bullying by peers (relative risk=2.47, 95% CI=1.74-3.52) were more likely to report psychotic symptoms at age 12 than were children who did not experience such traumatic events. The higher risk for psychotic symptoms was observed whether these events occurred early in life or later in childhood. The risk associated with childhood trauma remained significant in analyses controlling for children`s gender, socioeconomic deprivation, and IQ; for children`s early symptoms of internalizing or externalizing problems; and for children`s genetic liability to developing psychosis. In contrast, the risk associated with accidents was small (relative risk=1.47, 95% CI=1.02-2.13) and inconsistent across ages. Conclusions: Trauma characterized by intention to harm is associated with children`s reports of psychotic symptoms. Clinicians working with children who report early symptoms of psychosis should inquire about traumatic events such as maltreatment and bullying.

Hypoactive sexual desire disorder in a population-based study of Brazilian women: associated factors classified according to their importance

Objective: The etiology of hypoactive sexual desire disorder (HSDD) is known to be multifactorial, involving biological, psychosexual, and context-related factors. The objective of the present study was to analyze the factors associated with female HSDD and to stratify these factors according to their importance. Methods: This was a population-based, hierarchical study conducted in Brazil, based on data from previous research on the Brazilian Sexual Life Study, conducted between November 2002 and February 2003 in various Brazilian cities. The primary study consisted of a self-administered and anonymous questionnaire, addressing sociodemographic parameters, general health, life habits, behavior, and complaints related to sexual function. The association between HSDD and various other factors was assessed. The data were evaluated by hierarchical multiple regression analysis. Results: The prevalence of HSDD in this sample was 9.5%. Associations were found with cardiovascular disease, breast cancer, posttraumatic stress, poorer education level, being older, being married, a lack of information on sexuality in childhood/adolescence, and a limited sexual repertoire. Women who consumed moderate amounts of alcohol were found to be less likely to have HSDD. Conclusions: Analysis of the associated factors classified in order of importance and analysis of the characteristics of the sexual relationships provide additional information to currently available data on the traditional concepts of HSDD.

Effects of childhood development on late-life mental disorders

Purpose of review To explore recent findings bridging childhood development and common late-life mental disorders in the elderly. Recent findings We addressed aging as a part of the developmental process in central nervous system, typical and atypical neurodevelopment focusing on genetic and environmental risk factors and their interplay and links between psychopathology from childhood to the elderly, unifying theoretical perspectives and preventive intervention strategies. Summary Current findings suggest that childhood development is strictly connected to psychiatric phenotypes across the lifespan. Although we are far from a comprehensive understanding of mental health trajectories, some initial findings document both heterotypic and homotypic continuities from childhood to adulthood and from adulthood to the elderly. Our review also highlights the urgent need for investigations on preventive interventions in individuals at risk for mental disorders.

Etiological and Clinical Features of Childhood Psychotic Symptoms Results From a Birth Cohort

Context: It has been reported that childhood psychotic symptoms are common in the general population and may signal neurodevelopmental processes that lead to schizophrenia. However, it is not clear whether these symptoms are associated with the same extensive risk factors established for adult schizophrenia. Objective: To examine the construct validity of children`s self-reported psychotic symptoms by testing whether these symptoms share the risk factors and clinical features of adult schizophrenia. Design: Prospective, longitudinal cohort study of a nationally representative birth cohort in Great Britain. Participants: A total of 2232 twelve-year-old children followed up since age 5 years ( retention, 96%). Main Outcome Measure: Children`s self-reported hallucinations and delusions. Results: Children`s psychotic symptoms are familial and heritable and are associated with social risk factors (eg, urbanicity); cognitive impairments at age 5; home-rearing risk factors ( eg, maternal expressed emotion); behavioral, emotional, and educational problems at age 5; and comorbid conditions, including self-harm. Conclusions: The results provide a comprehensive picture of the construct validity of children`s self-reported psychotic symptoms. For researchers, the findings indicate that children who have psychotic symptoms can be recruited for neuroscience research to determine the pathogenesis of schizophrenia. For clinicians, the findings indicate that psychotic symptoms in childhood are often a marker of an impaired developmental process and should be actively assessed.

Association of the UGT1A1-53(TA)(n) polymorphism with L-thyroxine doses required for thyrotropin suppression in patients with differentiated thyroid cancer

There is a considerable interindividual variation in L-thyroxine [ 3,5,3`,5`-tetraiodo-l-thyronine (T(4))] dose required for thyrotropin (thyroid-stimulating hormone) suppression in patients with differentiated thyroid cancer. To investigate whether uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1)-mediated T(4) glucuronidation in liver affects T(4) dose, we genotyped 101 patients for the common UGT1A1-53(TA)(n) polymorphism and compared T(4) doses among patients having zero (5/6 and 6/6 genotypes), one (6/7 genotype), or two (7/7 and 7/8 genotypes) copies of the low-expression (TA) 7 and (TA) 8 alleles. A significant trend for decreasing T(4) dose with increasing number of copies of (TA)(7) and (TA)(8) (P = 0.037) and significant difference in T(4) dose across the UGT1A1-53(TA)(n) genotypes (P = 0.048) were observed, despite considerable overlap of T(4) doses among different genotypes. These results are consistent with reduced T(4) glucuronidation in patients with low-expression (TA) 7 and (TA) 8 alleles and provide the first evidence for association between UGT1A1-53(TA)(n) and T(4)-dose requirement for thyroid-stimulating hormone suppression in a natural clinical setting. Pharmacogenetics and Genomics 21: 341-343 (C) 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins. Pharmacogenetics and Genomics 2011, 21: 341-343

Association between micronuclei frequency in pollen mother cells of Tradescantia and mortality due to cancer and cardiovascular diseases: A preliminary study in Sao Jose dos Campos, Brazil

The present study was designed to explore the correlation between the frequency of micronuclei in Trad-MN, measured across 28 biomonitoring stations during the period comprised between 11 of May and 2 of October, 2006, and adjusted mortality rates due to cardiovascular, respiratory diseases and cancer in Sao Jose dos Campos, Brazil, an area with different sources of air pollution. For controlling purposes, mortality rate due to gastrointestinal diseases (an event less prone to be affected by air pollution) was also considered in the analysis. Spatial distribution of micronuclei frequency was determined using average interpolation. The association between health estimators and micronuclei frequency was determined by measures of Pearson`s correlation. Higher frequencies of micronuclei were detected in areas with high traffic and close to a petrochemical pole. Significant associations were detected between micronuclei frequency and adjusted mortality rate due to cardiovascular diseases (r = 0.841, p = 0.036) and cancer (r = 0.890, p = 0.018). The association between mortality due to chronic obstructive pulmonary diseases was positive but did not reach statistical significance (r = 0.640, p = 0.172), probably because of the small number of events. Gastrointestinal mortality did not exhibit significant association with micronuclei frequency. Because the small number of observations and the nature of an ecological study, the present findings must be considered with caution and considered as preliminary. Further studies, performed in different conditions of contamination and climate should be done before considering Trad-MN in the evaluation of human health risk imposed by air pollutants. (C) 2009 Elsevier Ltd. All rights reserved.

Esophageal cancer associated with chronic mucocutaneous candidiasis. Could chronic candidiasis lead to esophageal cancer?

Chronic mucocutaneous candidiasis (CMC) is a rare disease associated with immunodeficiency and characterized by persistent and refractory infections of the skin, appendages and mucous membranes caused by members of the genus Candida. Several different disorders are classified under this common denominator, including chronic and recurrent mucocutaneous infections due to Candida spp., which are sometimes linked to autoimmune endocrinopathies. These fungal infections are usually confined to the mucocutaneous surface, with little propensity for systemic disease or septicemia. We describe a patient with CMC who had an esophageal candidiasis refractory to treatment for decades and who developed an epidermoid esophageal cancer. No risk factors such as familiar susceptibility, smoking, alcohol drinking, or living in an endemic area were verified. This case report suggests the participation of nitrosamine compounds produced by chronic Candida infections as a risk factor for esophageal cancer in a patient with autosomal-dominant chronic mucocutaneous candidiasis.

Is Chlamydia-infected tubal fimbria the origin of ovarian cancer?

Ovarian cancer is a highly lethal disease and its underlying biology is poorly understood. Prophylactic salpingo-oophorectomies in BRCA + women have recently implicated the fimbria as a site of origin for high-grade serous carcinoma and its intraepithelial precursors. This suggests that at least some ovarian cancers, probably the most aggressive ones, may not originate in the ovary itself, but rather may arise in the uterine tubes. Chronic inflammation is associated with carcinogenesis in several tissues, including liver, esophagogastric junction (cardia), and the uterine cervix. The mechanisms underlying the relationship between inflammation and cancer are complex and involve common pathways, in addition to DNA damage. A critical source of uterine tube inflammation is infection with Chlamydia trachomatis. We hypothesize that C. trachomatis infection may be involved in chronic tubal, inflammation and subsequent fimbrial carcinogenesis. Fimbrial intraepithelial precursors can evolve into high grade serous carcinomas that spread rapidly to the ovarian surface and peritoneum; such tumors may appear to be primary ovarian neoplasia, though in reality being a secondary malignancy. This hypothesis must be further investigated to understand the intracellular signaling pathways involved in Chlamydia infection and its heating, and their relationship to carcinogenesis in order to discover potential therapeutic molecular targets. If our hypothesis were confirmed, salpingectomy instead of ovariectomy may also become the recommended surgery for high risk women. (C) 2008 Elsevier Ltd. All rights reserved.

PM(2.5) and PM(10): The influence of sugarcane burning on potential cancer risk

In Brazil, sugarcane fields are often burned to facilitate manual harvesting, and this burning causes environmental pollution from the large amounts of soot released into the atmosphere. This material contains numerous organic compounds such as PAHs. In this study, the concentrations of PAHs in two particulate-matter fractions (PM(2.5) and PM(10)) in the city of Araraquara (SE Brazil, with around 200,000 inhabitants and surrounded by sugarcane plantations) were determined during the sugarcane harvest (HV) and non-harvest (NHV) seasons in 2008 and 2009. The sampling strategy included four campaigns, with 60 samples in the NHV season and 220 samples in the HV season. The PM(2.5) and PM(10) fractions were collected using a dichotomous sampler (10 L min(-1), 24 h) with Teflon (TM) filters. The filter sets were extracted (ultrasonic bath with hexane/acetone (1:1 v/v)) and analyzed by HPLC/Fluorescence. The median concentration for total PAHs (PM(2.5) in 2009) was 0.99 ng m(-3) (NHV) and 3.3 ng m(-3) (HV). In the HV season, the total concentration of carcinogenic PAHs (benz(a)anthracene, benzo(b)fluoranthene, benzo(k)fluoranthene, and benzo(a)pyrene) was 5 times higher than in the NHV season. B(a)P median concentrations were 0.017 ng m(-3) and 0.12 ng m(-3) for the NHV and HV seasons, respectively. The potential cancer risk associated with exposure through inhalation of these compounds was estimated based on the benzo[a]pyrene toxic equivalence (BaP(eq)), where the overall toxicity of a PAR mixture is defined by the concentration of each compound multiplied by its relative toxic equivalence factor (TEF). BaP(eq) median (2008 and 2009 years) ranged between 0.65 and 1.0 ng m(-3) and 1.2-1.4 ng m(-3) for the NHV and HV seasons, respectively. Considering that the maximum permissible BaPeq in ambient air is 1 ng m(-3), related to the increased carcinogenic risk, our data suggest that the level of human exposure to PAHs in cities surrounded by sugarcane crops where the burning process is used is cause for concern. (C) 2010 Published by Elsevier Ltd.

Steroidogenic Factor 1 Overexpression and Gene Amplification Are More Frequent in Adrenocortical Tumors from Children than from Adults

Background: Steroidogenic factor 1 (SF-1) is a key determinant of endocrine development and function of adrenal cortex. SF-1 overexpression and gene amplification were previously demonstrated in a small group of pediatric adrenocortical tumors. Objective: Our objective was to determine the frequency of SF-1 protein expression and gene amplification in a large cohort of pediatric and adult adrenocortical tumors. Patients: SF-1 protein expression was assessed in a cohort of 103 adrenocortical tumors from 36 children and 67 adults, whereas gene amplification was studied in 38 adrenocortical tumors ( 17 from children). Methods: Tissue microarray, multiplex ligation-dependent probe amplification, and quantitative real-time PCR were used. Results: Astrong nuclear SF-1 expression was detected by tissue microarray in 56% (20 of 36) and 19% (13 of 67) of the pediatric and adult adrenocortical tumors, respectively (P = 0.0004). Increased SF-1 copy number was identified in 47% (eight of 17) and 10% (two of 21) of the pediatric and adult adrenocortical tumors, respectively (P = 0.02). All adrenocortical tumors with SF-1 gene amplification showed a strong SF-1 staining, whereas most of the tumors (61%) without SF-1 amplification displayed a weak or negative staining (P = 0.0008). Interestingly, a strong SF-1 staining was identified in five (29%) pediatric adrenocortical tumors without SF-1 amplification. The frequency of SF-1 overexpression and gene amplification was similar in adrenocortical adenomas and carcinomas. Conclusion: We demonstrated a higher frequency of SF-1 overexpression and gene amplification in pediatric than in adult adrenocortical tumors, suggesting an important role of SF-1 in pediatric adrenocortical tumorigenesis. (J Clin Endocrinol Metab 95: 1458-1462, 2010)