Case-control Comparison Research Articles

Medically unexplained visual loss in a specialist clinic: a retrospective case–control comparison

PurposeTo compare the clinical and demographic characteristics of adult patients with nonorganic or medically unexplained visual loss (MUVL) to those with other common conditions presenting to a neuro-ophthalmology clinic. MethodsCase–control design: a retrospective review of medical notes on a consecutive case series of 49 patients assessed at the King's College Hospital neuro-ophthalmology clinic with unexplained visual loss and matched with the next assessed patient identified from clinic records. Patients presented post-symptom onset with a mean clinical course of 30months (SD=67months) and standard clinical examination used to confirm diagnoses, alongside ancillary investigations if required. ResultsSeventy-two percent (n=36) of MUVL patients were female. In comparison with patients with organic visual disorders, MUVL cases presented with significantly higher rates of bilateral (cf. unilateral) visual impairment (41%, n=20), premorbid psychiatric (27%, n=13) as well as functional (24%, n=12) diagnoses and psychotropic medication usage (22%, n=11). Medically unexplained cases were significantly more likely to report preceding psychological stress (n=9; 18%). ConclusionsMedically unexplained visual impairment may be regarded as part of the spectrum of medically unexplained disorders seen in the general hospital setting. Research is needed to determine long-term outcomes and effective tailored interventions.

Cognitive and neuropsychiatric features of orthostatic tremor: A case–control comparison

IntroductionEvidence suggests that the cerebellum could play a role in the pathophysiology of orthostatic tremor. The link between orthostatic tremor and the cerebellum is of interest, especially in light of the role the cerebellum plays in cognition, and it raises the possibility that orthostatic tremor patients could have cognitive deficits consistent with cerebellar dysfunction. Our aim was to examine whether orthostatic tremor patients had cognitive deficits and distinct personality profiles when compared with matched controls. MethodsSixteen consecutive orthostatic tremor patients (65.7±13.3years) and 32 healthy matched controls underwent a neuropsychological battery and the Personality Assessment Inventory. In linear regression models, the dependent variable was each one of the neuropsychological test scores or the Personality Assessment Inventory subscales and the independent variable was orthostatic tremor vs. control. ResultsAdjusted for age in years, sex, years of education, comorbidity index, current smoker, and depressive symptoms, diagnosis (orthostatic tremor vs. healthy control) was associated with poor performance on tests of executive function, visuospatial ability, verbal memory, visual memory, and language tests, and on a number of the Personality Assessment Inventory subscales (somatic concerns, anxiety related disorders, depression, and antisocial features). Older-onset OT (>60years) patients had poorer scores on cognitive and personality testing compared with their younger-onset OT counterparts. ConclusionOrthostatic tremor patients have deficits in specific aspects of neuropsychological functioning, particularly those thought to rely on the integrity of the prefrontal cortex, which suggests involvement of frontocerebellar circuits. Cognitive impairment and personality disturbances could be disease-associated nonmotor manifestations of orthostatic tremor.

Genetic analysis of TREM2 variants in Chinese Han patients with sporadic Parkinson’s disease

Parkinson’s disease (PD) is the second most common neurodegenerative disorder after Alzheimer’s disease and is characterized by the degeneration of dopaminergic neurons in substantia nigra. Recently, rs75932628 (p.R47H) of the triggering receptor expressed on myeloid cells 2 gene (TREM2) was identified to be associated with PD in American, Spanish, Irish, and Polish population. To explore whether TREM2 variants are related to susceptibility of sporadic PD in Chinese Han population, we designed a case-control comparison study and studied two variants rs75932628 (p.R47H) and rs2234253 (p.T96K) of the TREM2 gene in 512 Chinese Han patients with sporadic PD and 512 age, gender and ethnicity matched normal controls from Mainland China. No variant for either rs75932628 or rs2234253 was found in both PD and control cohorts. Our data suggest that neither variant rs75932628 nor rs2234253 be a major susceptibility factor of sporadic PD in Chinese Han population from Mainland China.

The Finding of Del 17p in Marrow Plasma Cells from Patients with Light-Chain Amyloidosis (AL) May Confer a Worse Prognosis

The Finding of Del 17p in Marrow Plasma Cells from Patients with Light-Chain Amyloidosis (AL) May Confer a Worse Prognosis

Genetic analysis of MC1R variants in Chinese Han patients with sporadic Parkinson’s disease

Parkinson’s disease (PD, OMIM 168600) is a neurodegenerative disorder featured by degeneration of melanin-positive dopaminergic neurons. Epidemiologic studies have suggested that PD and malignant melanoma (MM) might share common genetic components. Recently, the p.R160W variant in the melanocortin 1 receptor gene (MC1R, OMIM 155555), a risk factor for MM, has been identified to be associated with PD in Spanish population. To explore whether the MC1R variants are associated with sporadic PD in Chinese population, we designed a case-control comparison study and studied three variants, including rs3212366 (p.F196L), rs33932559 (p.I120T) and rs34090186 (p.R67Q), in the MC1R gene in 512 Chinese Han patients with sporadic PD and 512 age, gender and ethnicity matched normal controls. For rs3212366, only the TT genotype was identified in both PD and control cohorts. For variants rs33932559 and rs34090186, we did not identify any statistically significant difference in either genotypic distribution or allelic distribution between the PD cohort and control cohort, and in addition, we did not identify any related haplotype that would either increase the risk for PD or play a protective role against PD. Our data suggest that none of the three variants of the MC1R gene and related haplotypes be associated with sporadic form of PD in Chinese Han population from Mainland China.

Aortic-to-brachial stiffness gradient independently predicts kidney function: Case-control comparison between patients with type 2 diabetes and non-diabetic controls

Aortic-to-brachial stiffness gradient independently predicts kidney function: Case-control comparison between patients with type 2 diabetes and non-diabetic controls

A prospective case control comparison of the ZeroGravity system versus a standard lead apron as radiation protection strategy in neuroendovascular procedures

Background and purposeWe aimed to compare the performance of the ZeroGravity (ZG) system (radiation protection system composed by a suspended lead suit) against the use of standard protection (lead apron...

Dietary patterns and CVD: a systematic review and meta-analysis of observational studies.

Epidemiological studies show that diet is linked to the risk of developing CVD. The objective of this meta-analysis was to estimate the association between empirically derived dietary patterns and CVD. PubMed was searched for observational studies of data-driven dietary patterns that reported outcomes of cardiovascular events. The association between dietary patterns and CVD was estimated using a random-effects meta-analysis with 95 % CI. Totally, twenty-two observational studies met the inclusion criteria. The pooled relative risk (RR) for CVD, CHD and stroke in a comparison of the highest to the lowest category of prudent/healthy dietary patterns in cohort studies was 0·69 (95% CI 0·60, 0·78; I 2=0%), 0·83 (95% CI 0·75, 0·92; I 2=44·6%) and 0·86 (95% CI 0·74, 1·01; I 2=59·5%), respectively. The pooled RR of CHD in a case-control comparison of the highest to the lowest category of prudent/healthy dietary patterns was 0·71 (95% CI 0·63, 0·80; I 2=0%). The pooled RR for CVD, CHD and stroke in a comparison of the highest to the lowest category of western dietary patterns in cohort studies was 1·14 (95% CI 0·92, 1·42; I 2=56·9%), 1·03 (95% CI 0·90, 1·17; I 2=59·4%) and 1·05 (95% CI 0·91, 1·22; I 2=27·6%), respectively; in case-control studies, there was evidence of increased CHD risk. Our results support the evidence of the prudent/healthy pattern as a protective factor for CVD.

FOC6-7LAT SOFTWARE INDUCED SAVINGS ON HOSPITAL COSTS OF ALCOHOL ADDICTS' CARE

Lesch Alcoholism Typology (LAT) is one of the most widely used clinical typologies of alcohol addiction. Study tested whether introduction of LAT software in clinical practice leaded to improved outcomes and reduced costs. Retrospective matched-pairs case-control cost comparison study was conducted at the Regional Addiction Center of the …

Abstract P174: Comparison of Groups With and Without Diabetes Mellitus and Preeclampsia in Pregnancy: A Retrospective Case-control Comparison

Objective: Preeclampsia (PreE) and diabetes mellitus (DM) in pregnancy share many risk factors and consequences. Thus, the interactions between these two disease-processes need to be further examined. We compared normal pregnancies to those complicated with preE, gestational diabetes (GDM), and/or pre-existing DM to assess the effect of DM on placental development and outcomes when this condition is complicated by preE. Methods: Chart reviews were performed in an IRB approved retrospective case-control design with pregnancies resulting in live born singletons. Total 178 subjects with preE with and without DM or GDM and live born singletons were selected from deliveries in 2008 through 2011 at Scott & White Memorial Hospital, Temple, Texas. These were compared to 443 without preE and with and without DM or GDM. Statistical analysis was performed using ANOVA and Duncan’s post-hoc test. Results: Patients who developed preE had higher systolic and diastolic pressures compared to groups without preE (p < 0.05). Patients with DM or GDM were older (p < 0.05). There was no difference among groups for gravidity (p = 0.21) with the average gravidity of 2.7 (1.8 SD) for 621 subjects having a range of 1 to 14 pregnancies. Patients with preE delivered earlier in pregnancy than those without preE regardless of diabetes status. However, those with preE and DM delivered earlier at 35.0 ± 0.4 weeks than the other two preE groups (p < 0.05), suggesting a more severe condition. Patients with DM who developed preE delivered smaller (p < 0.05) babies (correcting for gestational age at delivery) than those with DM without preE (1.00 ± 0.03 versus 1.16 ± 0.04, respectively). Development of GDM did not result in smaller babies for those pregnancies with preE (1.07 versus 1.09). Conclusions: The development of preE in those with pre-existing DM led to growth restriction and more severe disease as evidenced by lower birth weights corrected for gestational age and earlier gestational ages at delivery. These differences were not seen in GDM pregnancies. This observation supports the concept that elevated glucose levels during first trimester placental development may alter the placenta and lead to restriction later in pregnancy when a second stimulus triggers preE.

OPRK1 promoter hypermethylation increases the risk of Alzheimer’s disease

As a member of the opioid family, κ-opioid receptors play important role in cognitive and learning functions. The purpose of this study was to evaluate the association of OPRK1 promoter methylation with Alzheimer’s disease (AD). OPRK1 DNA methylation levels of 48 cases and 58 well matched controls were measured using the bisulphite pyrosequencing technology. Our results showed that there was a significant correlation between three CpG sites on the OPRK1 promoter region (r>=0.715, p<0.001). Thus, the mean methylation value of the three CpG sites was used for the case-control comparison. And our results showed there was a significantly higher OPRK1 promoter methylation in AD cases than in controls (p=0.006, adjusted p=0.012). Subsequent luciferase reporter assay showed the CpGs containing fragment of OPRK1 promoter significantly increased the expression of reporter gene (Fold=2.248, p=0.0235). In summary, our results suggested that OPRK1 promoter hypermethylation might increase the risk of AD through its regulation on the gene expression of OPRK1.

Abstract 4601: Genetic polymorphisms in the vitamin D pathway in relation to lung cancer risk and survival

Abstract Studies have suggested that vitamin D may have protective effects against cancer development or tumor progression. To search for additional evidence, we investigated the role of genetic polymorphisms involved in the vitamin D pathway in non-small cell lung cancer (NSCLC). We evaluated common genetic polymorphisms associated with the vitamin D pathway in relation to NSCLC in a case-control study of 603 newly diagnosed NSCLC patients and 661 matched healthy controls. Seven single nucleotide polymorphisms (SNPs) were genotyped, the expression of CYP27B1 and CYP24A1 were measured in 153 tumor samples and their associations with genotypes and patient survival were also analyzed. In the case-control comparison, we found SNP rs3782130 (CYP27B1), rs7041 (GC), rs6068816 and rs4809957 (CYP24A1) associated with NSCLC risk. The risk of NSCLC was increased with the number of risk alleles. CYP27B1 and CYP24A1 expression were significantly different between tumor and normal tissues in NSCLC. High CYP27B1 expression was associated with better overall survival, and the expression was different by the rs3782130 genotype. The study suggests that some genetic polymorphisms involved in the vitamin D pathway may associate with NSCLC risk, and one of the polymorphisms (rs3782130) may affect gene expression and patient survival. Note: This abstract was not presented at the meeting. Citation Format: Jinyu Kong, Fangxiu Xu, Jinli Qu, Yu Wang, Ming Gao, Herbert Yu, Biyun Qian. Genetic polymorphisms in the vitamin D pathway in relation to lung cancer risk and survival. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4601. doi:10.1158/1538-7445.AM2015-4601

Abstract 4625: Influence of intrinsic apoptotic pathway gene polymorphisms on the development and progression of acute myeloid leukemia: Case-control study

Abstract Background: Apoptosis plays a pivotal role in maintaining cellular homeostasis mainly in rapidly proliferating tissue like hematopoietic tissue. Defective apoptosis is one of the hallmarks of cancer as it plays a crucial role in malignant transformation through disruption of homeostasis mechanism resulting in acquired chemo-resistance. Aim: The functional single nucleotide polymorphisms (SNPs) in apoptotic genes can influence the gene expression leading to altered apoptosis that may promote malignancy. Moreover, these SNPs might also influence the treatment outcome, since most of the chemotherapeutic drugs being used are aimed to induce apoptosis of malignant cells. The present study mainly aims to evaluate the role of SNPs in BCL2 (-938C&amp;gt;A (rs2279115); BAX (-248G&amp;gt;A (rs4645878), CASP9 [-1263A&amp;gt;G (rs4645978); -712C&amp;gt;T (rs4645981); -293del (rs4645982); Ex5+32G&amp;gt;A (rs1052576)] with development of acute myeloid leukemia (AML) and treatment outcome in terms of disease free survival (DFS) among patients who have achieved complete remission(CR) rates after first induction chemotherapy. Methods: The study includes 225 AML cases and 307 age-gender matched controls for case-control comparison. The study was approved by ethical committee of Osmania University. Before collecting 5ml of blood sample, each participant had provided written informed consent. Baseline line clinical characteristics and follow-up data were collected from the tumor registries with the help of oncologist. Genomic DNA was extracted and SNPs were genotyped using PCR, RFLP, Tetra primer techniques. The genotype data was subjected to various statistical analyses to correlate with disease occurrence and treatment outcome in terms of CR and DFS rates using SPSS Software. We have also performed non parametric analysis to know gene-gene interaction through Multi Dimensionality Reduction (MDR). Results: The single SNP analysis had revealed that BCL2 (rs2279115), BAX (rs4645878), CASP9 (rs4645978) and CASP9 (rs4645982) were significantly associated with the origin of AML. Survival analysis had shown that minor alleles of both CASP9 (rs4645978 and rs4645982) SNPs were associated with reduced DFS rates (log rank p = 0.02). Further, cox regression analysis had also confirmed these observations where CASP9 rs4645978 (HR = 1.91; 95%CI = 1.19-3.07; p = 0.008) and rs4645982 (HR = 1.88; 95%CI = 1.06-3.35; p = 0.03) had elevated risk for relapse and shorter DFS rates. The MDR analysis had revealed that CASP9 (rs4645981) is the highest predicting variable. The best interaction model was found to be CASP9 (-1263A&amp;gt;G (rs4645978); -712C&amp;gt;T (rs4645981); and BCL2 (rs2279115) with CVC = 8/10 and TAB = 0.604. Conclusion: Our results suggest that CASP9 (rs4645978 and rs4645982) SNPs might influence the AML development and DFS rates after first induction chemotherapy. Citation Format: Anuradha Cingeetham, Sugunakar Vuree, Nageswara Rao Dunna, Manjula Gorre, Raghunadharao Digumarti, Sudha Sinha, Vishnupriya Satti. Influence of intrinsic apoptotic pathway gene polymorphisms on the development and progression of acute myeloid leukemia: Case-control study. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4625. doi:10.1158/1538-7445.AM2015-4625

O132. Comparison of groups with and without diabetes mellitus and preeclampsia in pregnancy: A retrospective case-control comparison

Objective Preeclampsia (PreE) and diabetes mellitus (DM) in pregnancy share many risk factors and consequences. Thus, the interactions between these two disease-processes need to be further examined. This study compared normal pregnancies to those complicated with preE, gestational diabetes, and/or pre-existing DM to assess the effect of elevated glucose on placental development and outcomes when this condition is complicated by the addition of preE. Methods Medical chart reviews were performed in an IRB approved retrospective case-control design with pregnancies resulting in live born singletons. Total 178 subjects with preE with and without diabetes in pregnancy and live born singletons were selected from deliveries in 2008 through 2011 at Scott & White Memorial hospital. These were compared to 443 without preE and with and without diabetes delivering at similar dates. Statistical analysis was performed using ANOVA and Duncan’s post-hoc test. Results Patients who developed preE during gestation had higher blood pressures for both systolic and diastolic compared to the groups who did not developed preE during pregnancies ( p p p = 0.21) with the average gravidity of 2.7 (1.8SD) for 621 subjects having a range of 1 to 14 pregnancies. Patients with preE delivered earlier in pregnancy than those without preE regardless of diabetes status. However, those with preE and pre-existing DM delivered significantly earlier at 35.0 ± 0.4 weeks than the other two preE groups ( p p Conclusions The development of preE in those with pre-existing DM led to growth restriction and more severe disease as evidenced by lower birth weights corrected for gestational age and earlier gestational ages at delivery. These differences were not seen in pregnancies where DM developed during the pregnancy. This observation supports the concept that elevated glucose levels during placental development in the first trimester may alter the placenta and lead to restriction later in pregnancy when a second stimulus triggers preE.

Rs7193343 polymorphism in zinc finger homeobox 3 (ZFHX3) gene and atrial fibrillation: an updated meta-analysis of 10 case-control comparisons.

BackgroundThe previous genome-wide studies have shown that rs7193343 single-nucleotide polymorphism (SNP) in zinc finger homeobox 3 (ZFHX3) gene correlate with risk of atrial fibrillation (AF). However, the distribution of this SNP differs significantly among various populations. The present study was to investigate whether combined evidence shows the association between ZFHX3 rs7193343 SNP and the risk of AF in various populations.MethodsA systematic search of all studies published through Dec 2014 was conducted using the Medline, Embase, WanFang, ScienceDirect, CNKI, and OVID databases. The case-control studies that evaluated an association between rs7193343 SNP and risk of AF were identified. The association between the ZFHX3 rs7193343 SNP and AF susceptibility was assessed using genetic models.ResultsWe collected 10 comparisons from six studies for rs7193343 SNP, including 1037 cases and 4310 controls in Asian, 5583 cases and 38215 controls in Caucasian, and then performed an updated meta-analysis and subgroup analysis based on ethnicity. In overall population, the occurrence of AF was found to be associated with T-allelic of rs7193343 SNP in ZFHX3 (OR =1.17, 95% CI 1.10-1.26). In subgroup analysis, we observed there was significant association between T-allele of rs7193343 and risk of AF in Caucasian subgroups (OR =1.20, 95% CI 1.12-1.30), but no statistically significance (OR = 1.07, 95% CI 0.92-1.24) in Asian population.ConclusionIn Caucasian population, genetic variant rs7193343 SNP is associated with risk of AF in Caucasian population. However, no association is found in Asian population based on the current evidence. Further studies with larger sample size involving case-control populations with multiple ethnics are still required in the future.

Investigation of the association between the fecal microbiota and breast cancer in postmenopausal women: a population-based case-control pilot study.

We investigated whether the gut microbiota differed in 48 postmenopausal breast cancer case patients, pretreatment, vs 48 control patients. Microbiota profiles in fecal DNA were determined by Illumina sequencing and taxonomy of 16S rRNA genes. Estrogens were quantified in urine. Case-control comparisons employed linear and unconditional logistic regression of microbiota α-diversity (PD_whole tree) and UniFrac analysis of β-diversity, with two-sided statistical tests. Total estrogens correlated with α-diversity in control patients (Spearman Rho = 0.37, P = .009) but not case patients (Spearman Rho = 0.04, P = .77). Compared with control patients, case patients had statistically significantly altered microbiota composition (β-diversity, P = .006) and lower α-diversity (P = .004). Adjusted for estrogens and other covariates, odds ratio of cancer was 0.50 (95% confidence interval = 0.30 to 0.85) per α-diversity tertile. Differences in specific taxa were not statistically significant when adjusted for multiple comparisons. This pilot study shows that postmenopausal women with breast cancer have altered composition and estrogen-independent low diversity of their gut microbiota. Whether these affect breast cancer risk and prognosis is unknown.

Identifying Etiologically Distinct Sub-Types of Cancer: A Demonstration Project Involving Breast Cancer.

With the advent of increasingly detailed molecular portraits of tumor specimens, much attention has been directed toward identifying clinically distinct subtypes of cancer. Subtyping of tumors can also be accomplished with the goal of identifying distinct etiologies. We demonstrate the use of new methodologies to identify genes that distinguish etiologically heterogeneous subtypes of breast cancer using data from the case–control Cancer and Steroid Hormone Study. Tumor specimens were evaluated using a breast cancer expression panel of 196 genes. Using a statistical measure that distinguishes the degree of etiologic heterogeneity in tumor subtypes, each gene is ranked on the basis of its ability to distinguish etiologically distinct subtypes. This is accomplished independently using case–control comparisons and by examining the concordance odds ratios in double primaries. The estrogen receptor gene, and others in this pathway with expression levels that correlated strongly with estrogen receptor levels, demonstrate high degrees of etiologic heterogeneity in both methods. Our results are consistent with a growing literature that confirms the distinct etiologies of breast cancers classified on the basis of estrogen receptor expression levels. This proof-of-principle project demonstrates the viability of new strategies to identify genomic features that distinguish subtypes of cancer from an etiologic perspective.

The impact of diabetes mellitus on outcomes of endoscopic sinus surgery: a nested case‐control study

Given the immune impairment associated with diabetes mellitus (DM), its impact on chronic rhinosinusitis (CRS) is a potentially relevant concern; however, it has not been well-studied. A single retrospective study reported worse postoperative quality of life outcomes in DM patients with CRS. Our study evaluated the effect of comorbid DM on outcomes of endoscopic sinus surgery (ESS) using a prospective study design. Using a multicentered, prospective cohort of patients (n = 437) undergoing ESS for recalcitrant CRS, a nested case-control comparison was performed between 20 adult DM patients (cases) and 20 non-DM patients (controls), matched 1:1 for age and Lund-Mackay computed tomography (CT) scores. Outcome measures included 22-item Sinonasal Outcome Test (SNOT-22), Rhinosinusitis Disability Index (RSDI), Patient Health Questionnaire (PHQ-2), and Brief Smell Identification Test (BSIT). Mean follow-up was similar between cases (mean ± standard deviation: 12.6 ± 6.0 months) and controls (12.9 ± 5.9 months; p = 0.862). All preoperative scores were statistically equivalent between DM and non-DM cohorts. Both cohorts showed significant post-ESS improvement in SNOT-22 (p = 0.001) and RSDI scores (p < 0.001), and no significant change in PHQ-2 or BSIT scores. The magnitude of score changes was statistically equivalent between the 2 cohorts for all outcome measures with no differences in postoperative score changes between insulin-dependent DM patients and those managed by oral hypoglycemics or dietary restriction (p ≥ 0.444). DM patients with CRS experience similar degrees of symptomatic benefit from ESS compared to controls. Insulin dependence does not appear to adversely affect surgical outcome but a larger cohort would better assess the effect of DM type and control on surgical outcomes in CRS.

Association of intracranial aneurysms and meningiomas: a case-control study.

The authors aimed to assess whether the prevalence of intracranial aneurysms in patients with intracranial meningiomas was higher than that in a healthy population. The authors performed a hospital-based case-control study of 300 patients with newly diagnosed intracranial meningiomas and 900 age- and sex-matched controls without a history of brain tumors to evaluate any associations between intracranial aneurysms and intracranial meningiomas. Unconditional multivariate logistic regression models were used for case-control comparisons. Intracranial aneurysms were identified in 23 patients (7.7%) and 24 controls (2.7%; p < 0.001). There was a significant association between intracranial aneurysms and intracranial meningiomas (OR 2.913, 95% CI 1.613-5.261) and hypertension (OR 1.905, 95% CI 1.053-3.446). In a subgroup analysis of the patients with newly diagnosed intracranial meningiomas, there was a significant association between intracranial aneurysms and hypertension (OR 2.876, 95% CI 1.125-7.352) and tumor volume (OR 1.012, 95% CI 1.001-1.024). These patients were also more likely than controls to have other intracranial vascular diseases (p < 0.001), such as isolated occlusion of the intracranial vessels, excluding intracranial aneurysms. The prevalence of intracranial aneurysms was higher in patients with intracranial meningiomas. Hypertension and tumor volume appear to be associated with the formation of intracranial aneurysms in these patients.

13 No molecular evidence for the role of the genetic background of the host in explaining lymph node metastasis in head and neck cancer

Introduction It has been shown for head and neck squamous cell carcinomas (HNSCC), that a specific gene expression profile in the primary tumor has predictive value for the presence of a lymph node metastasis. It is possible that these expression profiles are a result of acquired cancer-associated genetic aberrations during tumorigenesis. The alternative hypothesis, based on genetic studies in the mouse, is that the variation in the genome of the host determines the risk for metastasis. Aim of this study was to measure the global gene expression of the normal mucosa and the tumor as control of HNSCC patients to establish whether there is a difference between patients with and without lymph node metastasis. In addition, the paired analysis allowed the assessment of differential gene expression of HNSCC versus corresponding normal mucosa. Material and methods We examined the global gene expression of normal oral mucosa and the paired tumors from 22 HNSCC patients of whom eight patients were with and fourteen without lymph node metastasis. Five HNSCC were in the oropharynx and 17 in the oral cavity; only HPV-negative tumors were selected. Cross-validation was used to establish the predictive value of a gene expression profile. Results We showed in this case-control comparison that a gene expression profile in tumors had significant predictive value, as previously reported. When using expression profiles of the corresponding normal mucosa, however, the predictive value was lower and can be considered of little or no value for the prediction of lymph node status. Approximately 1600 unique and mapped transcripts were significantly and differentially expressed between tumor and mucosa, based on an p -value Conclusions This study provides evidence that the metastatic potential in HNSCC is likely the result of the cancer-associated genetic changes, and not related to the genetic variation in the host. Second, we obtained a comprehensive and valuable view on the gene expression difference between HNSCC and paired normal mucosal tissue.