Atypical protein kinase Cι (PKCι) has roles in cell growth, cellular polarity, and migration, and its abundance is frequently increased in cancer. We identified a protein interaction surface containing a dibasic motif (RIPR) that bound a distinct subset of PKCι substrates including lethal giant larvae 2 (LLGL2) and myosin X, but not other substrates such as Par3. Further characterization demonstrated that Arg471 in this motif was important for binding to LLGL2, whereas Arg474 was critical for interaction with myosin X, indicating that multiple complexes could be formed through this motif.
View Article and Find Full Text PDFObjective: Women with early cervical cancer or intraepithelial neoplasia grades 2 and 3 (CIN2+) are treated by conization; however, they still have a higher risk for subsequent CIN2+ than the general female population. Persistence of high-risk (HR) human papillomavirus (HPV) is a key factor in the development of CIN2+. We investigated persistence and reappearance of type-specific HR HPV infection after conization and evaluated possible co-factors.
View Article and Find Full Text PDFObjective: The role of human papillomavirus (HPV) in the pathogenesis of ovarian cancer is controversial, and conflicting results have been published. We conducted a systematic review and meta-analysis to estimate the prevalence of HPV in epithelial ovarian cancer tissue.
Material And Methods: Observational studies published until 4 March 2013 were identified in PubMed and Embase.
Background: In an attempt to decrease social disparities in cancer survival, it is important to consider the mechanisms by which socioeconomic position influences cancer prognosis. We aimed to investigate whether any associations between socioeconomic factors and survival after cervical cancer could be explained by socioeconomic differences in cancer stage, comorbidity, lifestyle factors or treatment.
Methods: We identified 1961 cases of cervical cancer diagnosed between 2005 and 2010 in the Danish Gynaecological Cancer database, with information on prognostic factors, treatment and lifestyle.
Background: Infection with high-risk (HR) human papillomavirus (HPV) is associated with penile cancer in men, cervical cancer in women, and anal cancer and certain types of head and neck cancers in both sexes. Few studies have assessed the prevalence and type distribution of HPV among men in sub-Saharan Africa, where the rates of HIV and penile and cervical cancer are high.
Material And Methods: We used data from a cross-sectional study among 1813 men in Tanzania.
Background: Survivors of childhood cancer are known to be at risk for long-term physical and mental effects. However, little is known about how cancers can affect mental health in the siblings of these patients. We aimed to assess the long-term risks of mental disorders in survivors of childhood cancer and their siblings.
View Article and Find Full Text PDFBackground: Human papillomavirus (HPV) is one of the most common sexually transmitted infections worldwide. The prevalence is dependent on several known factors notably sexual behavior and age, and factors still under scrutiny.
Objective: This study aimed to examine risk factors for high-risk (HR) HPV infection among HIV-positive and HIV-negative women from the general population of Tanzania and to assess whether specific risk factors could contribute to the high prevalence of HR HPV infection in older age found in some populations including Tanzanian women.
Objective: To estimate the incidence of pregnancy-associated cancer during a 30-year period in Denmark on the basis of both births and abortions with and without age adjustment and age standardization.
Methods: Using data from the nationwide Danish registries, we investigated the occurrence of pregnancy-associated cancer (defined as cancer diagnosed during pregnancy and up to 1 year after pregnancy has ended) in pregnancies resulting in a birth (live birth or stillbirth) or an abortion. We included patients with primary cancer diagnosed at ages 15-44 years during 1977-2006 according to the Danish Cancer Registry.
Objective: ABCB1 encodes the multi-drug efflux pump P-glycoprotein (P-gp) and has been implicated in multi-drug resistance. We comprehensively evaluated this gene and flanking regions for an association with clinical outcome in epithelial ovarian cancer (EOC).
Methods: The best candidates from fine-mapping analysis of 21 ABCB1 SNPs tagging C1236T (rs1128503), G2677T/A (rs2032582), and C3435T (rs1045642) were analysed in 4616 European invasive EOC patients from thirteen Ovarian Cancer Association Consortium (OCAC) studies and The Cancer Genome Atlas (TCGA).
Background: Few biomarkers of ovarian cancer prognosis have been established, partly because subtype-specific associations might be obscured in studies combining all histopathological subtypes. We examined whether tumour expression of the progesterone receptor (PR) and oestrogen receptor (ER) was associated with subtype-specific survival.
Methods: 12 studies participating in the Ovarian Tumor Tissue Analysis consortium contributed tissue microarray sections and clinical data to our study.
Background: A reduction in the incidence of genital warts (GWs) is one of the first markers of the effectiveness of vaccination against human papillomavirus (HPV) at the population level. The aim of this cohort study was to use individual information on HPV vaccination status to assess the effect on risk of GWs.
Methods: Population-based registries were used to identify all girls in the birth cohorts 1989-1999 in Denmark, and information about HPV vaccination was obtained for the period 2006-2012.
Introduction: Subcutaneous trunk abscesses are frequent, and current treatment options generally involve incision. By contrast, the standard care for breast abscesses is ultrasound-guided drainage. The aim of this study was to evaluate the feasibility of ultrasound-guided drainage combined with antibiotics in the treatment of subcutaneous abscesses on the trunk.
View Article and Find Full Text PDFUntreated, hypoparathyroidism (hypoPT) is a state of hypocalcemia with inappropriately low plasma parathyroid hormone (PTH) levels and hyperphosphatemia. PTH administration normalizes plasma calcium and phosphate levels and reduces the doses of calcium and active vitamin D analogues needed. To develop an evidence-based clinical algorithm to monitor hypoPT patients treated with recombinant human PTH (rhPTH[1-84]) injected subcutaneously in the thigh, we performed a 24-hour monitoring study of pharmacokinetic and pharmacodynamic effects in a group of 38 patients who had completed a 6-month randomized study on effects of treatment with a fixed rhPTH(1-84) dose of 100 µg/d or similar placebo as an add-on to conventional treatment.
View Article and Find Full Text PDFObjective: Routine identification of nutritional risk screening is paramount as the first stage in nutritional treatment of the elderly. The major focus of former validation studies of screening tools has been on the ability to predict undernutrition. The aim of this study was to validate Mini Nutritional Assessment-Short Form (MNA-SF), the Malnutrition Universal Screening Tool (MUST), the Nutritional Risk Screening 2002 (NRS-2002), Body Mass Index (BMI) <24, and the Eating Validation Scheme (EVS), using published randomized controlled trials of nutritional intervention among old people in primary health care, in order to evaluate whether they were capable of distinguishing those with a positive benefit from those that showed no benefit of nutritional intervention.
View Article and Find Full Text PDFSignaling through G proteins normally involves conformational switching between GTP- and GDP-bound states. Several Rho GTPases are also regulated by RhoGDI binding and sequestering in the cytosol. Rnd proteins are atypical constitutively GTP-bound Rho proteins, whose regulation remains elusive.
View Article and Find Full Text PDFPurpose: The aim of the study was to examine the potential association between a history of pelvic inflammatory disease (PID) and risk of epithelial ovarian cancer or ovarian borderline tumors.
Methods: In a population-based case-control study in Denmark, we included 554 women with invasive ovarian cancer, 202 with ovarian borderline tumors, and 1,564 controls aged 35-79 years. The analyses were performed in multiple logistic regression models.
The primary objective of this study was to assess the expression of MIB-1 (Ki-67) in tumour tissues from 808 patients with epithelial ovarian tumours. The second was to evaluate, whether MIB-1 (Ki-67) tissue expression levels correlate with clinicopathological parameters and prognosis of the disease. Using tissue arrays (TA), we analysed the MIB-1 (Ki-67) expression levels in tissues from 202 women with borderline ovarian tumours (BOT) (177 stage I, 5 stage II, 19 stage III, 1 stage IV) and 606 ovarian cancer (OC) patients (177 stage I, 64 stage II, 311 stage III, 54 stage IV).
View Article and Find Full Text PDFAims: Relational strain may be a risk factor for relapse after smoking cessation whereas social support may be protective. This study aimed to assess which aspects of social relations were associated with smoking abstinence among ever-smokers.
Methods: This cross-sectional questionnaire study included data from two large Danish cohorts: One including younger women (n=10,107) and one including older men (n=21,091) and women (n=23,800).
Background: Tubal ligation is a protective factor for ovarian cancer, but it is unknown whether this protection extends to all invasive histological subtypes or borderline tumors. We undertook an international collaborative study to examine the association between tubal ligation and ovarian cancer subtypes.
Methods: We pooled primary data from 13 population-based case-control studies, including 10,157 patients with ovarian cancer (7942 invasive; 2215 borderline) and 13,904 control women.
Objective: To clarify the association between fertility treatment and the risk for cancer in children.
Design: Meta-analysis.
Setting: None.
TERT-locus SNPs and leukocyte telomere measures are reportedly associated with risks of multiple cancers. Using the Illumina custom genotyping array iCOGs, we analyzed ∼480 SNPs at the TERT locus in breast (n = 103,991), ovarian (n = 39,774) and BRCA1 mutation carrier (n = 11,705) cancer cases and controls. Leukocyte telomere measurements were also available for 53,724 participants.
View Article and Find Full Text PDFGenome-wide association studies (GWAS) have identified four susceptibility loci for epithelial ovarian cancer (EOC), with another two suggestive loci reaching near genome-wide significance. We pooled data from a GWAS conducted in North America with another GWAS from the UK. We selected the top 24,551 SNPs for inclusion on the iCOGS custom genotyping array.
View Article and Find Full Text PDFHNF1B is overexpressed in clear cell epithelial ovarian cancer, and we observed epigenetic silencing in serous epithelial ovarian cancer, leading us to hypothesize that variation in this gene differentially associates with epithelial ovarian cancer risk according to histological subtype. Here we comprehensively map variation in HNF1B with respect to epithelial ovarian cancer risk and analyse DNA methylation and expression profiles across histological subtypes. Different single-nucleotide polymorphisms associate with invasive serous (rs7405776 odds ratio (OR)=1.
View Article and Find Full Text PDFEpithelial ovarian cancer (EOC) has a heritable component that remains to be fully characterized. Most identified common susceptibility variants lie in non-protein-coding sequences. We hypothesized that variants in the 3' untranslated region at putative microRNA (miRNA)-binding sites represent functional targets that influence EOC susceptibility.
View Article and Find Full Text PDFBackground: Ovarian cancer is a leading cause of cancer-related death among women. In an effort to understand contributors to disease outcome, we evaluated single-nucleotide polymorphisms (SNP) previously associated with ovarian cancer recurrence or survival, specifically in angiogenesis, inflammation, mitosis, and drug disposition genes.
Methods: Twenty-seven SNPs in VHL, HGF, IL18, PRKACB, ABCB1, CYP2C8, ERCC2, and ERCC1 previously associated with ovarian cancer outcome were genotyped in 10,084 invasive cases from 28 studies from the Ovarian Cancer Association Consortium with over 37,000-observed person-years and 4,478 deaths.