Gender-adjusted Odds Ratios Research Articles

A Comprehensive Analysis of Skin Cancer Concerns and Protective Practices in Manitoba, Canada, Highlights Lack of Skin Cancer Awareness and Predominance of High-Risk Sun Exposure Behaviors.

The rapidly increasing skin cancer rates in Canada are alarming, with current data estimating that 1/3 of Canadians will be affected in their lifetime. Thus, deeper understanding of high-risk sun exposure behaviors is needed to help counter this trend. Only limited action has been taken by federal/provincial governments to reduce skin cancer incidence. A cross-sectional survey study was conducted in Manitoba, with frequency counts, means, and percentages used to encapsulate responses. Age- and gender-adjusted odds ratios were calculated using logistic regression analyses. Our study identified worrying inadequacies in sun protective behaviors and attitudes, with the threat of such high-risk behaviors amplified by a lack of skin cancer awareness. Alarming elements were noted in participants' sun exposure history (>65% reported a history of sunburns, >50% previously used a tanning bed, and >75% recently tanned for pleasure), beliefs and attitudes (>50% believe that they look better/healthier with a tan, and >40% believe that having a base tan is protective against further sun damage), and sun protection efforts (sun protective clothing was used <60% of the time, sunscreen was used by <50%, and there was a lack of knowledge about sunscreen characteristics in ~30% of respondents), in addition to significant differences being established between demographic subgroups (based on gender, age, skin phototype, income, and education attained). This study provides worrisome insight onto the grim landscape of sun protective behaviors and attitudes in Manitoba, which will inevitably translate into higher skin cancer rates and should serve as a call to action to promote targeted public health messaging in this jurisdiction and beyond.

Cannabis use and associated factors among 15-16-year-old adolescents in Estonia 2003-2019: Results from cross-sectional ESPAD surveys.

Aims:(1) To describe the time trends of monthly cannabis use and (2) to analyse the association between the trends of monthly cannabis use and trends of different explanatory factors among adolescents in Estonia in 2003–2019.Methods:Nationally representative data from five waves of the cross-sectional European School Survey Project on Alcohol and Other Drugs (ESPAD) among 15–16-year-old adolescents (n = 11,348) in Estonia were analysed. Tests for trends were used to assess significant changes in monthly cannabis use and explanatory variables over time. Logistic regression analysis was used to analyse the association between monthly cannabis use and perceived easiness of getting cannabis, perceived health risk of cannabis use, parental factors, risk behaviours, and leisure time activities. The model included interaction terms between the study year and each explanatory variable. Gender-adjusted odds ratios (OR) with 95% confidence intervals (CI) were calculated.Results:Monthly cannabis use increased from 5.3% in 2003 to 7.7% in 2015 and thereafter decreased to 6.6% in 2019 among adolescents in Estonia (P = 0.007). The association between monthly cannabis use and alcohol use was significant over the study period and the interaction of alcohol use with study year indicated significantly increased effect of alcohol use over time (P = 0.038). The association between monthly cannabis use and perceived easiness of obtaining cannabis, perceived low health risk from cannabis use and smoking was significant, but remained unchanged over the study period. The relationship between monthly cannabis use and low parental control was significant in two last study years but did not show any changes over time.Conclusions:The findings of this study demonstrate the need for the implementation of multi-component substance use prevention programmes among adolescents in Estonia that also pay attention to the factors associated with the cannabis use.

Macronutrients Intake and Stomach Cancer Risk in Iran: A Hospital-based Case-Control Study.

Background: Stomach cancer (SC) is one of the most common cancers in the world. Dietary risk factors of SC are not fully understood. This study aimed to investigate the association between macronutrient intakes and the risk of SC. Study design: A hospital-based case-control study. Methods: The data were obtained from a hospital-based case-control study conducted at the Cancer Institute of Iran from 2010 to 2012. Patients were 40 years or older and were diagnosed with SC in less than one year with no history of any cancers. On the other hand, the controls were healthy subjects who were caregivers or visitors of the patients. Demographic characteristics were collected using a structured questionnaire through face to face interviews by trained interviewers. Dietary data were obtained using a validated Diet History Questionnaire. The age and gender-adjusted odds ratios (ORs), as well as the adjusted ORs of age, gender, energy, education, smoking, and body mass index, were reported for continuous and tertiles of intakes. Results: Totally, 207 SC patients and 217 controls participated in this study. In the full adjusted model, after comparing the highest tertiles to the lowest ones, the intake of sucrose (OR: 2.94; 95% CI: 1.66-5.19; P-trend<0.001), protein (OR: 2.04; 95% CI: 1.17-3.55; P-trend=0.011), cholesterol (OR: 2.22; 95% CI: 1.28-3.85; P-trend=0.005), and percent of calories from protein (OR: 3.09; 95% CI: 1.69-5.61; P-trend<1.001) showed a positive significant association with SC. Moreover, a significantly negative association was found between the percent of calories obtained from carbohydrates and SC (OR: 0. 57; 95% CI: 0.33-0.98; P-trend=0.015). Conclusion: The findings in this study showed that macronutrient intakes might be associated with the etiology of SC in Iran.

Macronutrients Intake and Stomach Cancer Risk in Iran: A Hospital-based Case-Control Study

Background: Stomach cancer (SC) is one of the most common cancers in the world. Dietary risk factors of SC are not fully understood. This study aimed to investigate the association between macronutrient intakes and the risk of SC. Study design: A hospital-based case-control study. Methods: The data were obtained from a hospital-based case-control study conducted at the Cancer Institute of Iran from 2010 to 2012. Patients were 40 years or older and were diagnosed with SC in less than one year with no history of any cancers. On the other hand, the controls were healthy subjects who were caregivers or visitors of the patients. Demographic characteristics were collected using a structured questionnaire through face to face interviews by trained interviewers. Dietary data were obtained using a validated Diet History Questionnaire. The age and gender-adjusted odds ratios (ORs), as well as the adjusted ORs of age, gender, energy, education, smoking, and body mass index, were reported for continuous and tertiles of intakes. Results: Totally, 207 SC patients and 217 controls participated in this study. In the full adjusted model, after comparing the highest tertiles to the lowest ones, the intake of sucrose (OR: 2.94; 95% CI: 1.66-5.19; P-trend<0.001), protein (OR: 2.04; 95% CI: 1.17-3.55; P-trend=0.011), cholesterol (OR: 2.22; 95% CI: 1.28-3.85; P-trend=0.005), and percent of calories from protein (OR: 3.09; 95% CI: 1.69-5.61; P-trend<1.001) showed a positive significant association with SC. Moreover, a significantly negative association was found between the percent of calories obtained from carbohydrates and SC (OR: 0. 57; 95% CI: 0.33-0.98; P-trend=0.015). Conclusion: The findings in this study showed that macronutrient intakes might be associated with the etiology of SC in Iran.

Can I Discharge My Stroke Patient Home After Inpatient Neurorehabilitation? LIMOS Cut-Off Scores for Stroke Patients "Living Alone" and "Living With Family".

Background: Discharge planning of stroke patients during inpatient neurorehabilitation is often difficult since it depends both on the patient's ability to perform activities of daily living (ADL) and the social context. The aim of this study was to define ADL cut-off scores using the Lucerne ICF-based multidisciplinary observation scale (LIMOS) that allow the clinicians to decide whether stroke patients who “live alone” and “live with a family” can be discharged home or must enter a nursing home. Additionally, we investigated whether age and gender factors influence these cut-off scores.Methods: A single-center retrospective cohort study was conducted to establish cut-off discharge scores for the LIMOS. Receiver-operating-characteristics curves were calculated for both patient groups “living alone” and “living with family” to illustrate the prognostic potential of the LIMOS total score with respect to their discharge goals (home alone or nursing home; home with family or nursing home). A logistic regression model was used to determine the (age- and gender-adjusted) odds ratios of being released home if the LIMOS total score was above the cut-off. A single-center prospective cohort study was then conducted to verify the adequacy of the cut-off values for the LIMOS total score.Results: A total of 687 stroke inpatients were included in both studies. For the group “living alone” a LIMOS total score above 158 indicated good diagnostic accuracy in predicting discharge home (sensitivity 93.6%; specificity 95.4%). A LIMOS total cut-off score above 130 points was found for the group “living with family” (sensitivity 92.0%; specificity 88.6%). The LIMOS total score odds ratios, adjusted for age and gender, were 292.5 [95% CI: (52.0–1645.5)] for the group “living alone” and were 89.4 [95% CI: (32.3–247.7)] for the group “living with family.”Conclusion: Stroke survivors living alone needed a higher ADL level to return home than those living with a family. A LIMOS total score above 158 points allows a clinician to discharge a patient that lives alone, whereas a lower LIMOS score above 130 points can be sufficient in a patient that lives with a family. Neither age nor gender played a significant role.

The association between anxiety and esophageal cancer: A nationwide population-based study.

Research on generalized anxiety disorder (GAD) and its association with esophageal cancer (EC) is sparse. The study aimed to explore the association between GAD and EC. A multicenter, population-based study in high-risk regions for EC (ECHRRs) was conducted from 2017 to 2019. All participants received free endoscopy screening. If the esophageal endoscopy results were suspicious, the pathological biopsy was performed to confirm normal, esophagitis, low-grade intraepithelial neoplasia (LGIN), high-grade intraepithelial neoplasia (HGIN), and EC. Information on participants' exposure to risk factors was collected. GAD was assessed with Generalized Anxiety Disorder Scale-7. With esophageal endoscopy, 25,650 participants in ECHRRs were examined, 9586 of whom were suspicious and confirmed by esophageal pathology. The detection rate of EC and precancerous lesions was 6.83% (1751/25,650), with 1377 LGIN (5.37%), 272 HGIN (1.06%), and 102 EC (0.40%) cases. The overall mean GAD score (95% CI) and prevalence among 25,650 participants with endoscopy were 1.96 (1.93-1.99) and 16.90%, respectively. The mean GAD score and prevalence among 9586 participants with pathology were 1.96 (1.91-2.02) and 17.98%, respectively. The mean GAD scores of patients confirmed with normal, esophagitis, LGIN, HGIN, and EC were 1.73 (1.62-1.85), 1.91 (1.85-1.97), 1.94 (1.80-2.08), 3.98 (3.73-4.23). and 2.97 (2.49-3.45), respectively (p < 0.001). The corresponding prevalence of GAD were 5.21%, 18.72%, 17.72%, 43.75%, and 36.27%, respectively (p < 0.001). The age- and gender-adjusted odds ratios (ORs) between GAD and each esophageal lesion type were 1.02 (0.99-1.04), 1.01 (0.98-1.04), 1.27 (1.21-1.33), and 1.16 (1.08-1.24), respectively. The ORs (95% CIs) of the positive associations were 1.08 (1.05-1.12), 1.03 (0.99-1.07), 1.35 (1.29-1.42), and 1.19 (1.10-1.29) after further adjustment for potential confounders (all p < 0.001). Sensitivity analysis showed that the positive association persisted. GAD was significantly higher in patients with EC and precancerous lesions. Focusing on and alleviating anxiety in high-risk groups (including patients with HGIN and EC) may be an effective strategy for EC prevention and control. Further prospective studies are warranted to validate the results.

Risk Factors for Stroke in Rural Population of Telangana State of India, an Unmatched Case Control Study.

Context Stroke tops the list of causes for acquired disability among adults and is the second leading cause of death worldwide. Evidence from developed countries indicate significant decline in stroke incidence and mortality, attributable to prevention of risk factors in general population. There is limited evidence on risk factors for stroke in rural India. Aims This study aims to ascertain the risk factors for stroke in rural Telangana and provide a guide to health care providers in adopting treatment and prevention strategies. Settings and Design The study was conducted in the Moinabad mandal of Ranga Reddy District, Telangana state of India. This is a population based unmatched case–control study. Methods and Materials All the houses of Moinabad were approached by a door-to-door survey to identify cases. A total of 288 persons were enrolled in the study which included 144 cases and 144 controls. Statistical Analysis To derive age and gender adjusted odds ratios of various risk factors, binary logistic regression analysis was performed. Results The estimated crude prevalence of stroke in Moinabad mandal is 257 per lakh population. Modifiable risk factors identified were, total cholesterol, systolic blood pressure, alcohol consumption, smoking, diastolic blood pressure, low high-density lipoprotein cholesterol, and central obesity as measured by waist circumference. Nonmodifiable risk factors identified were male gender and higher age group. Conclusion The high prevalence of stroke in rural Telangana makes it an important public health challenge for the state. The identified risk factors need to be addressed at population level.

Factors Associated With Low Lean Mass in Early Rheumatoid Arthritis: A Cross- Sectional Study.

Background and Objectives: The aim of the study was to evaluate body composition (BC) of rheumatoid arthritis (RA) patients at disease onset compared to population controls focusing on the associations between low lean mass and disease specific parameters, nutritional factors and physical activity. Materials and Methods: 91 patients with early rheumatoid arthritis (ERA) (72% female) and 328 control subjects (54% female) were studied. BC-lean and fat mass parameters were measured with a Lunar Prodigy Dual Energy X-Ray Absorptiometry (DXA) machine. The prevalence, age and gender adjusted odds ratios of having low lean mass and overfat, associations between nutrition, physical activity, and ERA disease specific parameters and the presence of low lean mass were evaluated. Results: We found that the BC of patients with recent onset RA differs from control subjects—ERA patients had a higher mean body fat percentage (BFP) and lower appendicular lean mass (ALM). 41.8% of the ERA patients and 19.8% of the controls were classified as having low lean mass adjusted OR 3.3 (95% C.I. 1.9–5.5, p < 0.001). 68.1% of the ERA subjects and 47.3% of the controls were overfat (adjusted OR 1.9 (95% C.I. 1.1–3.3, p = 0.02)) and the adjusted odds of having both low lean mass and overfat were 4.4 times higher (26.4% vs. 7.0% 95% C.I. 2.3–8.4, p < 0.001) among the ERA group. Higher ESR (OR 1.03, C.I. 1.002–1.051, p = 0.03), CRP (OR 1.03, C.I. 1.002–1.061, p = 0.04), lower protein intake (OR 0.98 C.I. 0.96–0.99, p = 0.04), corticosteroid usage (OR 3.71 C.I. 1.4–9.9, p < 0.01) and lower quality of life (higher HAQ score OR 2.41 C.I. 1.24–4.65, p < 0.01) were associated with having low lean mass in the ERA group (adjusted to age and gender). Conclusions: Patients with early RA have lower appendicular lean mass and higher body fat percentage compared to healthy controls. Loss of lean mass in early RA is associated with elevated inflammatory markers inducing catabolism, lower protein intake and also with GCS treatment.

Work-related determinants of psychosocial risk factors among employees in the hospital setting.

Understanding which factors influence occupational safety and health risks is crucial to promote psychosocial risk management. To assess the main work-related determinants of high exposure to psychosocial risk factors among Portuguese employees in the hospital setting. Between May and July 2014, 399 employees of a public hospital completed a structured questionnaire. Psychosocial factors were assessed by the Portuguese medium length version of the Copenhagen Psychosocial Questionnaire. Age and gender adjusted odds ratios (OR) and 95% confidence intervals (95% CI) were computed by logistic regression models. The highest psychosocial risks emerged in the p ersonality (53.8%), workplace demands (28.1%), and social relationships and leadership (24.4%) categories. Professionals with non-health care roles presented a higher risk in the worker-work interface (OR = 2.60;95% CI:1.02-6.62), that evaluated work insecurity, satisfaction and the work-family interface. Shift workers were exposed to a higher psychosocial risk in workplace demands (OR = 1.79;95% CI:1.10-2.91), personality (OR = 2.45;95% CI:1.36-4.41), and health and well-being (OR = 3.18; 95% CI:1.72-5.66). Non-government employees had a higher risk exposure in personality (OR = 2.20;95% CI:1.15-4.21), and those who were absent from work in personality (OR = 2.62;95% CI:1.41-4.86), and health and wellbeing (OR = 2.34;95% CI:1.27-4.31). Employees working in the hospital setting are vulnerable to psychosocial risk factors. Identifying those risks contributes to optimize workers' psychosocial health, increasing the effectiveness of the organization.

Lead exposure may affect gingival health in children

BackgroundSeveral studies have reported the harmful effects of lead poisoning. However, the relationship between lead exposure and oral health of children has not been well defined. The aim of this study was to investigate the relationship between blood lead level (BLL) and oral health status of children.MethodsA total of 351 children (aged 7–15 years) were recruited from the pilot data of the Korean Environmental Health Survey in Children and Adolescents, which was designed to examine environmental exposure and children’s health status in South Korea. Blood samples were taken to determine BLLs and oral examinations were performed to assess oral health parameters, including community periodontal index (CPI), gingival index (GI), and plaque index (PI). Information regarding socioeconomic status, oral hygiene behavior, and dietary habits was collected from parents and guardians.ResultsThe participants were divided equally into four quartiles, with quartile I comprised of children with the lowest BLLs. There were significant differences for PI (p < 0.05) among the quartile groups. Using logistic regression models, we found a significant relationship between BLL and oral health parameters. The crude odds ratios for CPI, GI, and PI in the third quartile were 5.24 (95% CI: 1.48-18.56), 4.35 (95% CI: 1.36-13.9), and 4.17 (95% CI: 1.50-11.54), respectively, while the age and gender-adjusted odds ratios were 7.66 (95% CI: 1.84-31.91), 6.80 (95% CI: 1.80-25.68), and 3.41 (95% CI: 1.12-10.40), respectively. After adjustments for age, gender, parent education level, and frequency of tooth brushing, the adjusted odds ratios were 7.21 (95% CI: 1.72-30.19), 6.13 (95% CI: 1.62-23.19), and 3.37 (95% CI: 1.10-10.34), respectively.ConclusionsA high BLL might be associated with oral health problems in children, including plaque deposition and gingival diseases.

Smoking among adults with and without disabilities in the UK.

The health risks of cigarette smoking are well established. As a result, reducing cigarette smoking is a key concern for public health agencies. Little is known about rates of smoking among adults with disabilities. Secondary analysis of data collected in Waves 2 and 7 of 'Understanding Society', an annual household panel study. Age and gender adjusted odds ratios (AORs) of adults with disabilities smoking increased significantly from 1.41 (1.33-1.49) in 2010-12 to 1.57 (1.45-1.70) in 2015-17 (P = 0.032). AORs of adults with disabilities smoking 20 or more cigarettes a day increased non-significantly from 1.83 (1.66-2.02) in 2010-12 to 1.90 (1.65-2.20) in 2015-17. These changes were evident for both men and women and across age groups. Additionally adjusting these estimates to take account of between group differences in socioeconomic position significantly reduced the AORs for both smoking outcomes. Changes over time in AORs reflected a more rapid decline in smoking among participants without a disability. Adults with disabilities are more likely than their peers to smoke. Public health agencies and practitioners may wish to consider what reasonable adjustments may need to be made to policies and interventions to ensure that they are effective for adults with disabilities.

Cohort Effects in the Prevalence and Survival of People with Dementia in a Rural Area in Northern Sweden.

Recent studies suggest that trends in cardiovascular risk may result in a decrease in age-specific prevalence of dementia. Studies in rural areas are rare. To study cohort effects in dementia prevalence and survival of people with dementia in a Swedish rural area. Participants were from the 1995-1998 Nordanstig Project (NP) (n = 303) and the 2001-2003 Swedish National study on Aging and Care in Nordanstig (SNAC-N) (n = 384). Overall 6-year dementia prevalence and mortality in NP and SNAC-N were compared for people 78 years and older. Logistic regression analyses were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for dementia occurrence using the NP study population as the reference group. Cox regression models were used to analyze time to death. The crude prevalence of dementia was 21.8% in NP and 17.4% in SNAC-N. When the NP cohort was used as the reference group, the age- and gender-adjusted OR of dementia was 0.71 (95% CI 0.48-1.04) in SNAC-N; the OR was 0.47 (0.24-0.90) for men and 0.88 (0.54-1.44) for women. In the extended model, the OR of dementia was significantly lower in SNAC-N than in the NP cohort as a whole (0.63; 0.39-0.99) and in men (0.34; 0.15-0.79), but not in women (0.81; 0.46-1.44). The Cox regression models indicated that the hazard ratio of dying was lower in the SNAC-N than NP population. Trends toward a lower prevalence of dementia in high-income countries seem to be evident in this Swedish rural area, at least in men.

Platelet transfusions in platelet consumptive disorders are associated with arterial thrombosis and in-hospital mortality

AbstractWhile platelets are primary mediators of hemostasis, there is emerging evidence to show that they may also mediate pathologic thrombogenesis. Little data are available on risks and benefits associated with platelet transfusions in thrombotic thrombocytopenic purpura (TTP), heparin-induced thrombocytopenia (HIT) and immune thrombocytopenic purpura (ITP). This study utilized the Nationwide Inpatient Sample to evaluate the current in-hospital platelet transfusion practices and their association with arterial/venous thrombosis, acute myocardial infarction (AMI), stroke, and in-hospital mortality over 5 years (2007-2011). Age and gender-adjusted odds ratios (adjOR) associated with platelet transfusions were calculated. There were 10 624 hospitalizations with TTP; 6332 with HIT and 79 980 with ITP. Platelet transfusions were reported in 10.1% TTP, 7.1% HIT, and 25.8% ITP admissions. Platelet transfusions in TTP were associated with higher odds of arterial thrombosis (adjOR = 5.8, 95%CI = 1.3-26.6), AMI (adjOR = 2.0, 95%CI = 1.2-3.3) and mortality (adjOR = 2.0,95%CI = 1.3-3.0), but not venous thrombosis. Platelet transfusions in HIT were associated with higher odds of arterial thrombosis (adjOR = 3.4, 95%CI = 1.2-9.5) and mortality (adjOR = 5.2, 95%CI = 2.6-10.5) but not venous thrombosis. Except for AMI, all relationships remained significant after adjusting for clinical severity and acuity. No associations were significant for ITP. Platelet transfusions are associated with higher odds of arterial thrombosis and mortality among TTP and HIT patients.

Vitamin D and health-related quality of life in a community sample of older Canadians.

PurposeTo assess how vitamin D status is associated with health-related quality of life (HRQOL) among older residents of Canada.DesignWe analysed baseline data of 1,493 Canadians aged 50 years and over in Alberta on HRQOL (EQ-5D-5L) and serum 25-hydroxyvitamin D (25(OH)D) as a measure of vitamin D status. We applied multivariable regression methods to examine the association between vitamin D status and each of the five dimensions and the summary index of the EQ-5D-5L.ResultsParticipants with higher serum 25(OH)D levels were significantly less likely to report problems with mobility, usual activities, and depression and anxiety. Specifically, age- and gender-adjusted odds ratios for reporting problems with mobility, usual activities, and depression and anxiety were 0.58 (95 % confidence interval 0.44–0.78), 0.67 (0.50–0.89), and 0.67 (0.51–0.88) per 100 nmol/L increase in 25(OH)D, respectively. No significant associations were observed for problems with self-care and with pain and discomfort. HRQOL scores combining the responses of each of the five dimensions increased significantly with increasing serum 25(OH)D levels.ConclusionsThis is the first study to reveal the importance of vitamin D for the five dimensions of HRQOL in a community-based sample. The observed associations of vitamin D and HRQOL call for intervention studies to strengthen the evidence of the potential benefits of vitamin D supplementation for HRQOL among older adults.

Metabolic risk factors and masked hypertension in the general population: the Finn-Home study

The association between masked hypertension and metabolic syndrome (MS) or insulin resistance is unclear. We investigated an untreated nationwide population sample (n = 1582, age 44-74 years). Duplicate office blood pressure (BP) measurements were taken on one visit and duplicate morning and evening home measurements were taken for 7 days. Masked hypertension was defined as office BP < 140/90 mm Hg with home BP ⩾ 135/85 mm Hg. Logistic regression analysis was used to determine the association between masked hypertension and metabolic risk factors. Age- and gender-adjusted odds ratios for metabolic disorder were 2.89 (1.87-4.47), 2.93 (2.15-3.97) and 1.68 (1.05-2.70) in white-coat hypertension, 3.39 (2.00-5.76), 3.86 (2.61-5.72) and 2.77 (1.63-4.70) in masked hypertension, and 7.38 (5.19-10.49), 6.45 (4.92-8.46) and 4.27 (3.00-6.08) in sustained hypertension using European Group for the Study of Insulin Resistance, harmonised MS and homeostasis model assessment of insulin resistance above the 80th percentile criteria. When home BP was used to define MS, masked hypertension moved close to sustained hypertension. The association between masked hypertension and metabolic disorders was related to home BP, body mass index and waist circumference. In conclusion, home BP appears to be a useful method to assess the risk of metabolic disorder. Masked hypertensives would benefit from the use of home BP in the definition of MS.

Circadian pathway genes in relation to glioma risk and outcome.

There is growing evidence that circadian disruption may alter risk and aggressiveness of cancer. We evaluated common genetic variants in the circadian gene pathway for associations with glioma risk and patient outcome in a US clinic-based case-control study. Subjects were genotyped for 17 candidate single nucleotide polymorphisms in ARNTL, CRY1, CRY2, CSNK1E, KLHL30, NPAS2, PER1, PER3, CLOCK, and MYRIP. Unconditional logistic regression was used to estimate age and gender-adjusted odds ratios (OR) and 95% confidence intervals (CI) for glioma risk under three inheritance models (additive, dominant, and recessive). Proportional hazards regression was used to estimate hazard ratios for glioma-related death among 441 patients with high-grade tumors. Survival associations were validated using The Cancer Genome Atlas (TCGA) dataset. A variant in PER1 (rs2289591) was significantly associated with overall glioma risk (per variant allele OR 0.80; 95% CI 0.66-0.97; p trend=0.027). The variant allele for CLOCK rs11133391 under a recessive model increased risk of oligodendroglioma (OR 2.41; 95% CI 1.31-4.42; p=0.005), though not other glioma subtypes (p for heterogeneity=0.0033). The association remained significant after false discovery rate adjustment (p=0.008). Differential associations by gender were observed for MYRIP rs6599077 and CSNK1E rs1534891 though differences were not significant after adjustment for multiple testing. No consistent mortality associations were identified. Several of the examined genes exhibited differential expression in glioblastoma multiforme versus normal brain in TCGA data (MYRIP, ARNTL, CRY1, KLHL30, PER1, CLOCK, and PER3), and expression of NPAS2 was significantly associated with a poor patient outcome in TCGA patients. This exploratory analysis provides some evidence supporting a role for circadian genes in the onset of glioma and possibly the outcome of glioma.

Abstract 104: Toenail iron, genetic variation in iron status, and the risk and outcome of glioma .

Abstract Elevated iron stores can trigger overproduction of reactive oxygen species and induce oxidative DNA damage. To our knowledge, no studies have investigated the association of body iron stores with the risk of glioma. In this investigation, we examined single nucleotide polymorphisms (SNPs) identified as markers of iron status in genome-wide association studies, and also measured iron stores in toenail samples in a clinic-based case-control study conducted at medical centers in the southeastern US. Genotyping was performed in 622 newly diagnosed, nonrecurrent glioma cases (including 341 WHO grade IV glioblastomas (GBM); 146 WHO grade II or III astrocytomas, 94 mixed oligoastrocytomas (MOAs) and oligodendrogliomas, and 41 gliomas with unspecified histology) and 628 healthy controls with no history of brain tumors. Illumina GoldenGate and Taqman OpenArray assays were used to genotype oral DNA samples. A total of 24 SNPs associated with markers of iron status were genotyped. Iron levels in toenail samples were measured in 200 glioma cases and 200 controls using neutron-activation analysis. Logistic regression was used to estimate age and gender-adjusted odds ratios (OR) and 95% confidence intervals (CI) for glioma risk according to examined genotypes and toenail iron levels. Proportional hazards regression was used to estimate age and gender-adjusted hazard ratios (HR) for glioma-related death among 320 patients with GBM or high grade astrocytomas all treated with the current standard of care for high grade glioma (eg. surgery, radiation and temozolomide) (248 deaths; median Kaplan-Meier survival: 15.0 months). We observed no overall association with glioma risk or patient outcome for SNPs in ARSB, BTN1A1, C7ORF10, FLJ43390, GHR, GTSCR1, HFE, HIST1H2BJ, KRT18P33, LRRC16, SCGN, SLC17A1, TOPBP1, and WTAP. Among non-GBM astrocytomas, borderline risk associations were observed for rs236918 in PCSK7 (G&amp;gt;C; minor allele frequency (MAF) = 0.11) (per variant allele OR = 0.50; 95% CI: 0.29 to 0.88; p for trend = 0.01) and with rs1049296 in TF (C&amp;gt;T; MAF = 0.17) (recessive model OR = 3.03; 95% CI: 1.11 to 8.27; p = 0.03). Among oligodendrogliomas/MOAs, risk associations were observed for rs4820268 in TMPRSS6 (A&amp;gt;G; MAF = 0.43) (recessive model OR = 1.91; 95% CI: 1.14 to 3.22; p = 0.01) and rs12216125 in TRIM38 (C&amp;gt;T; MAF = 0.35) (dominant model OR = 1.67; 95% CI: 1.03 to 2.72; p = 0.04). No SNPs were associated with the risk of GBM. One SNP, rs972275 in RSPO3 (G&amp;gt;C; MAF = 0.38), was associated with shorter patient survival (dominant model HR = 1.40; 95% CI: 1.06, 1.87; p=0.02). Increasing levels of toenail iron was associated with a non-significant decrease in glioma risk (OR = 0.88; 95% CI: 0.77 to 1.02; p = 0.08). Iron levels were not associated with survival. To our knowledge this is the first report suggesting that genetically determined variation in iron status may affect glioma risk and patient outcome. Further studies are needed to confirm these results. Citation Format: Gabriella M. Anic, Reid C. Thompson, L. Burton Nabors, Jeffrey J. Olson, Melissa H. Madden, James E. Browning, John D. Brockman, Peter A. Forsyth, Kathleen M. Egan. Toenail iron, genetic variation in iron status, and the risk and outcome of glioma . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 104. doi:10.1158/1538-7445.AM2013-104

An exploratory analysis of common genetic variants in the vitamin D pathway including genome-wide associated variants in relation to glioma risk and outcome

Experimental and epidemiological evidence shows a beneficial role of vitamin D in cancer. In vitro evidence is consistent with a similar protective function in glioma; however, no study has yet examined the potential role of vitamin D in glioma. We evaluated the association between common genetic variants in the vitamin D pathway and glioma risk and patient outcome in 622 newly diagnosed glioma cases and 628 healthy controls enrolled in a clinic-based case-control study. Subjects were genotyped for 7 candidate and tagging single nucleotide polymorphisms in the vitamin D receptor and 8 additional variants in NADSYN1, GC, CYP24A1, CYP2R1, and C10ORF88 linked in genome-wide association studies to serum concentrations of vitamin D. Unconditional logistic regression was used to estimate age- and gender-adjusted odds ratios and 95% confidence intervals for glioma risk according to vitamin D genotypes. Proportional hazards regression was used to estimate hazard ratios for glioma-related death among 320 patients diagnosed with high-grade tumors. P values were uncorrected for multiple comparisons. Risk of astrocytic tumors was associated with variant alleles in rs3829251 (NADSYN1), rs10741657 (CYP2R1), rs2228570 (Fok1, VDR), and rs731236 (Taq1, VDR). No risk associations were found among oligodendroglial tumors. Survival associations were observed according to variant status for rs1544410 (Bsm1, VDR) and rs6013897 (CYP24A1). This exploratory analysis provides limited evidence of a role for genetic variation in vitamin D pathway genes with glioma risk and survival.

Abstract 2629: Common genetic variants in the vitamin D pathway including genome-wide associated variants in relation to glioma risk and outcome

Abstract Experimental and clinical evidence suggest that vitamin D protects against several types of cancer by promoting cell differentiation and apoptosis and by inhibiting cell proliferation and angiogenesis. In vitro evidence supports a similar protective function in glioma; however, no study has examined whether common genetic variants in the vitamin D pathway are related to glioma risk or patient outcome. We evaluated these potential associations in a clinic-based case-control study conducted at medical centers in the southeastern US. Genotyping was performed in 623 newly diagnosed (eg. nonrecurrent) glioma cases (including 343 WHO grade IV glioblastomas (GBM); 148 WHO grade II or III astrocytomas, 95 oligoastrocytomas and oligodendrogliomas, and 37 gliomas with unspecified histology) and 631 healthy controls with no history of brain tumors. A total of 7 candidate tagging single nucleotide polymorphisms (SNPs) were genotyped in the vitamin D receptor (VDR at 12q13) including rs2107301, rs2238135, rs4516035, rs731236 (Taq1), rs1544410 (Bsm1), rs11568820 (Cdx2), and rs2228570 (Fok1). SNPs associated with serum concentrations of 25-hydroxy vitamin D in genome-wide association studies (GWAS) were also evaluated including rs1155563, rs12512631, rs2282679, and rs7041 in GC (4q12-q13), rs10741657 in CYP2R1 (11p15), rs6013897 in CYP24A1 (20q13), rs3829251 in NADSYN1 (11q13), and rs6599638 at C10orf88 (10q26). Genotyping was performed in oral DNA samples using Illumina GoldenGate and Taqman OpenArray assays. Logistic regression was used to estimate age and gender-adjusted odds ratios (OR) and 95% confidence intervals (CI) for glioma risk according to vitamin D genotypes. Proportional hazards regression was used to estimate age and gender-adjusted hazard ratios (HR) for glioma-related death among 439 patients with high grade tumors including GBM and high grade astrocytomas (331 deaths; median Kaplan-Meier survival: 15.0 months). GWAS SNPs in NADSYN1, GC, and C10ORF88 were not associated with glioma risk or patient survival. Risk associations limited to GBM were observed for rs2238135 in the VDR (G&amp;gt;C; minor allele frequency (MAF) = 0.20) (per variant allele OR = 1.31; 95% CI: 1.01 to 1.71; p for trend = 0.04) and for GWAS SNP rs10741657 located near CYP2R1 (G&amp;gt;A; MAF = 0.40) (per variant allele OR = 0.79; 95% CI: 0.63 to 0.98; p for trend = 0.03). The variant allele in CYP24A1 rs6013897 (T&amp;gt;A; MAF = 0.20) was associated with prolonged survival among patients with high grade tumors (per variant allele HR = 0.79; 95% CI: 0.59 to 0.97; p for trend = 0.03) in patients uniformly treated with the current standard of care (surgery, radiation and temozolomide). To our knowledge this is the first report suggesting that genetic variation in vitamin D related genes may be a determinant of glioma risk and outcome. Further studies are needed to confirm these results and identify the putative causal variant. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2629. doi:1538-7445.AM2012-2629

Subjective symptoms related to depression and suicidal risk in a Japanese community: a cross-sectional study

BACKGROUND: This cross-sectional study aimed to assess the association between self-reported somatic and mental symptoms and the presence of major depressive disorder (MDD) and suicidal risk among community dwellers in Japan. METHODS: From two locations in Japan, we recruited 734 community dwellers who underwent an annual health screening. Basic symptoms of MDD, dysthymia, and the presence of associated suicidal risk were determined using a brief structured diagnostic psychiatric interview, Mini International Neuropsychiatric Interview (MINI). Information regarding self-reported somatic and mental symptoms was obtained from a self-administered questionnaire used in the annual health check-up. Suicidal risk was evaluated on the basis of six relevant questions asked in MINI. Logistic regression model was used to calculate age- and gender-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for MDD. Further adjustment for basic symptoms of MDD was performed to calculate ORs and CIs for suicidal risk. RESULTS: A myriad of somatic symptoms, including headache, heavy headedness, eye strain, and shoulder stiffness [adjusted OR (95% CI), 11.4 (1.22 - 107) at location 1; 5.17 (1.23 - 21.7) at location 2], were associated with the presence of MDD. Dysmenorrhea [6.07 (1.14 - 32.3) at location 1] and dysesthesia, arthralgia, and swelling in the extremities [2.72 (1.14 - 6.47) at location 2] were significantly associated with an increase in suicidal risk, independent of the presence of basic symptoms of MDD. CONCLUSION: Several somatic symptoms, especially pain-related ones, may serve as possible signs of depression and suicidal risk among community dwellers.