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Type 1 diabetes (T1D) results from poorly defined interaction between susceptibility genes and environmental factors. The objective was to investigate Human Leukocyte Antigens (HLA) associated T1D risk among Pakistani newborns in Norway based on what published globally. DNA samples from 189 newborns, whose parents were first generation migrants from Pakistan, were analyzed. The hypothesis was tested using high resolution HLA genotyping for the -DRB1 and -DQB1 loci and high/intermediate for the -DQA1 locus. We identified 28 different DRB1, 13 DQB1 and 9 DQA1 alleles. Of the 39 different haplotypes identified, only five have been reported to confer T1D susceptibility. Among these the DR3-DQ2 (DRB1*03:01:01-DQA1*05-DQB1*02:01:01) haplotype was found in 18.5% (n=70) of the newborns, and 18.6% (n=13) of these were homozygotes. A diverse range of HLA haplotypes were identified amongst an ethnically homogenous group of newborns, with only a small proportion associated with T1D risk. The incidence of T1D among immigrants form South/East Asia is the lowest in the Norwegian Type 1 Diabetes Registry. The few included so far, are children of first generation immigrants. If incidence of T1D rises in the Norwegian Pakistani childhood population, as observed in the UK, then environmental triggers rather than genetic susceptibility will be the explanation., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Earlier studies have shown raised risks of leukaemia and non-Hodgkin lymphoma in children, teenagers and young adults resident either at birth or diagnosis in Seascale. Some increases in cancer risk in these age groups have also been noted among those living around Dounreay. We aimed to update previous analyses relating to areas close to these nuclear installations by considering data from an additional 16 years of follow-up., Methods: Cross-sectional analyses compared cancer incidence rates for 1963-2006 among those aged 0-24 years at diagnosis living in geographically specified areas around either Sellafield or Dounreay with general population rates. Cancer incidence for the period 1971-2006 among the cohort of Cumbrian births between 1950 and 2006 was compared to national incidence for 1971-2006 using person-years analysis. Cancer among those born in the postcode sector closest to Dounreay was compared with that among those born in the three adjoining postcode sectors. Analyses considered both cancer overall and ICD-O-3 defined diagnostic subgroups including leukaemia, central nervous system tumours and other malignancies., Results: Apart from previously reported raised risks, no new significantly increased risks for cancer overall or any diagnostic subgroup were found among children or teenagers and young adults living around either nuclear installation. Individuals born close to the installations from 1950 to 2006 were not shown to be at any increased risk of cancer during the period 1971 to date., Conclusions: Analysis of recent data suggests that children, teenagers and young adults currently living close to Sellafield and Dounreay are not at an increased risk of developing cancer. Equally, there is no evidence of any increased cancer risk later in life among those resident in these areas at birth.

Objective: We aimed to assess the association of oral health (OH), dental care (DC) and mouthwash with upper-aerodigestive tract (UADT) cancer risk, and to examine the extent that enzymes involved in the metabolism of alcohol modify the effect of mouthwash., Materials and Methods: The study included 1963 patients with incident cancer of the oral cavity, oropharynx, hypopharynx, larynx or esophagus and 1993 controls. Subjects were interviewed about their oral health and dental care behaviors (which were converted to scores of OH and DC respectively), as well as smoking, alcohol drinking, diet, occupations, medical conditions and socio-economic status. Blood samples were taken for genetic analyses. Mouthwash use was analyzed in relation to the presence of polymorphisms of alcohol-metabolizing genes known to be associated with UADT. Adjusted odds ratios (ORs) and 95%-confidence intervals [CI] were estimated with multiple logistic regression models adjusting for multiple confounders., Results: Fully adjusted ORs of low versus high scores of DC and OH were 2.36[CI=1.51-3.67] and 2.22[CI=1.45-3.41], respectively, for all UADT sites combined. The OR for frequent use of mouthwash use (3 or more times/day) was 3.23[CI=1.68-6.19]. The OR for the rare variant ADH7 (coding for fast ethanol metabolism) was lower in mouthwash-users (OR=0.53[CI=0.35-0.81]) as compared to never-users (OR=0.97[CI=0.73-1.29]) indicating effect modification (pheterogeneity=0.065) while no relevant differences were observed between users and non-users for the variant alleles of ADH1B, ADH1C or ALDH2., Conclusions: Poor OH and DC seem to be independent risk factors for UADT because corresponding risk estimates remain substantially elevated after detailed adjustment for multiple confounders. Whether mouthwash use may entail some risk through the alcohol content in most formulations on the market remains to be fully clarified., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Numbers of children and young people with life-limiting conditions are rising, and increasing lifespans require young adults with life-limiting condition to transit to appropriate adult services., Aim: To describe the prevalence of life-limiting condition in children and young adults by age, sex, diagnostic group, ethnicity and deprivation., Design: A secondary analysis of the English Hospital Episode Statistics dataset was undertaken to calculate prevalence per 10,000 population., Setting/participants: Individuals (0-40 years) with life-limiting conditions were identified within an English Hospital Episode Statistics dataset by applying a customised coding framework of International Classification of Diseases, 10th Edition, disease codes., Results: There were 462,962 inpatient hospital admissions for 92,129 individual patients with a life-limiting condition. Prevalence-by-age group curve is U shaped with the highest overall prevalence in the under 1-year age group (127.3 per 10,000), decreasing until age 21-25 years (21.1 per 10,000) before rising steeply to reach 55.5 per 10,000 in the 36-40 -year age group. The distribution by diagnostic group varies by age: congenital anomalies are most prevalent in children until age 16-20 years with oncology diagnoses then becoming the most prevalent., Conclusion: Non-malignant diagnoses are common in children and young adults, and services that have historically focussed on oncological care will need to widen their remit to serve this population of life-limited patients. The diagnosis determining a patient's life-limiting condition will strongly influence their palliative care service needs. Therefore, understanding the diagnostic and demographic breakdown of this population of teenagers and young adults is crucial for planning future service provision.

Background: Artificial fluoridation of drinking water to improve dental health has long been a topic of controversy. Opponents of this public health measure have cited the possibility of bone cancer induction. The study objective was to examine whether increased risk of primary bone cancer was associated with living in areas with higher concentrations of fluoride in drinking water., Methods: Case data on osteosarcoma and Ewing sarcoma, diagnosed at ages 0-49 years in Great Britain (GB) (defined here as England, Scotland and Wales) during the period 1980-2005, were obtained from population-based cancer registries. Data on fluoride levels in drinking water in England and Wales were accessed through regional water companies and the Drinking Water Inspectorate. Scottish Water provided data for Scotland. Negative binomial regression was used to examine the relationship between incidence rates and level of fluoride in drinking water at small area level., Results: The study analysed 2566 osteosarcoma and 1650 Ewing sarcoma cases. There was no evidence of an association between osteosarcoma risk and fluoride in drinking water [relative risk (RR) per one part per million increase in the level of fluoride = 1·001; 90% confidence interval (CI) 0·871, 1·151] and similarly there was no association for Ewing sarcoma (RR = 0·929; 90% CI 0·773, 1·115)., Conclusions: The findings from this study provide no evidence that higher levels of fluoride (whether natural or artificial) in drinking water in GB lead to greater risk of either osteosarcoma or Ewing sarcoma.

Background: Tumours of the central nervous system are the second most common group of childhood cancers in 0-14 year olds (24% of total cancers) and represent a major diagnostic group in 15-24 year olds. The pilot case-control study aimed to establish methodologies for a future comprehensive aetiological investigation among children and young adults., Methods: Eligible cases were newly diagnosed with an intracranial tumour of neuroepithelial tissue aged 0-24 years. The pilot recruited patients through Leeds and Manchester Principal Treatment Centres. Controls were drawn from general practice lists. Controls were frequency matched by age and gender., Results: We interviewed 49 cases and 78 controls comprising 85% of the target sample size. Response rates were 52% for cases and 32% for controls. Completion of the questionnaire was successful, with a very small proportion of missing data being reported (5-10%). The age distribution of cases and controls was similar with around three-quarters of interviewed subjects aged 0-14. Half of cases and almost two-thirds of controls reported using a mobile phone with the majority starting between 10-14 years of age. Prevalence of breastfeeding was lower in cases than controls (Odds Ratio 0.4; 95% CI 0.2-1.2), whilst cases were more likely to be delivered by caesarean section (OR 1.6; 95% CI 0.6-4.4). Cases were significantly more likely to have a birthweight > 3.5 kg compared to controls. Cases were also more likely to come from a family with 3 or more siblings than controls (OR 3.0; 95% CI 0.7-13.6). The majority of participants (>80%) were in favour of taking either blood or saliva to aid molecular epidemiological research., Conclusions: Successful methods were established for identifying and recruiting a high proportion of case subjects, exploiting strong links with the clinical teams at the treatment centres. Control procedures proved more difficult to implement. However, working closely with national clinical and professional research networks will enable improved control identification and recruitment, with good prospects for collecting biological samples in the future.

Although previous studies on tobacco and alcohol and the risk of upper-aerodigestive-tract (UADT) cancers have clearly shown dose-response relations with the frequency and duration of tobacco and alcohol, studies on addiction to tobacco smoking itself as a risk factor for UADT cancer have not been published, to our knowledge. The aim of this report is to assess whether smoking addiction is an independent risk factor or a refinement to smoking variables (intensity and duration) for UADT squamous cell carcinoma (SCC) risk in the multicenter case-control study (ARCAGE) in Western Europe. The analyses included 1,586 ever smoking UADT SCC cases and 1,260 ever smoking controls. Addiction was measured by a modified Fagerström score (first cigarette after waking up, difficulty refraining from smoking in places where it is forbidden and cigarettes per day). Adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for UADT cancers with addiction variables were estimated with unconditional logistic regression. Among current smokers, the participants who smoked their first cigarette within 5 min of waking up were two times more likely to develop UADT SCC than those who smoked 60 min after waking up. Greater tobacco smoking addiction was associated with an increased risk of UADT SCC among current smokers (OR = 3.83, 95% CI: 2.56-5.73 for score of 3-7 vs. 0) but not among former smokers. These results may be consistent with a residual effect of smoking that was not captured by the questionnaire responses (smoking intensity and smoking duration) alone, suggesting addiction a refinement to smoking variables., (Copyright © 2013 UICC.)

Background: Congenital anomalies are a leading cause of infant death and disability and their incidence varies between ethnic groups in the UK. Rates of infant death are highest in children of Pakistani origin, and congenital anomalies are the most common cause of death in children younger than 12 in this ethnic group. We investigated the incidence of congenital anomalies in a large multiethnic birth cohort to identify the causes of the excess of congenital anomalies in this community., Methods: We obtained questionnaire data from the mothers of children with one or more anomalies from the Born in Bradford study, a prospective birth cohort study of 13,776 babies and their families in which recruitment was undertaken between 2007 and 2011. Details of anomalies were prospectively reported to the study and we cross checked these details against medical records. We linked data for anomalies to maternal questionnaire and clinical data gathered as part of the Born in Bradford study. We calculated univariate and multivariate risk ratios (RRs) with 95% CIs for various maternal risk factors., Findings: Of 11,396 babies for whom questionnaire data were available, 386 (3%) had a congenital anomaly. Rates for congenital anomaly were 305·74 per 10,000 livebirths, compared with a national rate of 165·90 per 10,000. The risk was greater for mothers of Pakistani origin than for those of white British origin (univariate RR 1·96, 95% CI 1·56-2·46). Overall, 2013 (18%) babies were the offspring of first-cousin unions. These babies were mainly of Pakistani origin--1922 (37%) of 5127 babies of Pakistani origin had parents in first-cousin unions. Consanguinity was associated with a doubling of risk for congenital anomaly (multivariate RR 2·19, 95% CI 1·67-2·85); we noted no association with increasing deprivation. 31% of all anomalies in children of Pakistani origin could be attributed to consanguinity. We noted a similar increase in risk for mothers of white British origin older than 34 years (multivariate RR 1·83, 95% CI 1·14-3·00). Maternal education to degree level was protective (0·53, 95% CI 0·38-0·75), irrespective of ethnic origin., Interpretation: Consanguinity is a major risk factor for congenital anomaly. The risk remains even after adjustment for deprivation, and accounts for almost a third of anomalies in babies of Pakistani origin. High levels of educational attainment are associated with reduced risk in all ethnic groups. Our findings will be valuable in health promotion and public health, and to those commissioning antenatal, paediatric, and clinical genetic services. Sensitive advice about the risks should be provided to communities at increased risk, and to couples in consanguineous unions, to assist in reproductive decision making., Funding: National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care programme., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objective: To investigate the effect of out-of-hours and winter admissions, and unit size on risk adjusted mortality in pediatric intensive care., Study Design: A national pediatric intensive care clinical audit provided data on over 86000 admissions to 29 pediatric intensive care units (2006-2011). Multivariate logistic regression modeled risk adjusted mortality prior to discharge with out-of-hours (night, weekend, public holiday) admissions, admissions per unit, winter admission, and potential confounders, overall and separately for emergency and planned admissions., Results: Nearly one-half (47.1%) of admissions were out-of-hours (n = 40948) and 79.2% of those were emergencies. Mortality for all out-of-hours admissions was raised (OR 1.1; 95% CI 1.02-1.2; P = .013), accounted for by planned admissions (OR 1.99; 95% CI 1.67-2.37; P < .001) compared with a reduced risk for emergency admissions (OR 0.93; 95% CI 0.86-1.1; P = .07). Winter admissions were associated with increased risk. Unit size did not affect mortality., Conclusions: A child admitted to pediatric intensive care as an out-of-hours emergency is not at increased risk of dying compared with a weekday daytime admission, indicating pediatric intensive care units provide consistent quality of care around the clock. Excess mortality in planned out-of-hours admissions may be explained by admissions following complex operations where risk-adjustment models underestimate the true probability of mortality. In winter, a time of seasonally high bed occupancy, there was an increased mortality risk, an effect which requires further investigation. Despite the different characteristics of small units, the absence of any effect of unit size on mortality suggests that number of admissions per unit does not influence standards of care., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Background: Previous studies have shown markedly lower birth weight among infants of South Asian origin compared with those of White European origin. Whether such differences mask greater adiposity in South Asian infants and whether they persist across generations in contemporary UK populations is unclear. Our aim was to compare birth weight, skinfold thickness and cord leptin between Pakistani and White British infants and to investigate the explanatory factors, including parental and grandparental birthplace., Methods: We examined the differences in birth weight and skinfold thickness between 4649 Pakistani and 4055 White British infants born at term in the same UK maternity unit and compared cord leptin in a subgroup of 775 Pakistani and 612 White British infants., Results: Pakistani infants were lighter (adjusted mean difference -234 g 95% CI -258 to -210) and were smaller in both subscapular and triceps skinfold measurements. The differences for subscapular and triceps skinfold thickness (mean z-score difference -0.27 95% CI -0.34 to -0.20 and -0.23 95% CI -0.30 to -0.16, respectively) were smaller than the difference in birth weight (mean z-score difference -0.52 95% CI -0.58 to -0.47) and attenuated to the null with adjustment for birth weight (0.03 95% CI -0.03 to 0.09 and -0.01 95% CI -0.08 to 0.05, respectively). Cord leptin concentration (indicator of fat mass) was similar in Pakistani and White British infants without adjustment for birth weight, but with adjustment became 30% higher (95% CI 17% to 44%) among Pakistani infants compared with White British infants. The magnitudes of difference did not differ by generation., Conclusions: Despite being markedly lighter, Pakistani infants had similar skinfold thicknesses and greater total fat mass, as indicated by cord leptin, for a given birth weight than White British infants. Any efforts to reduce ethnic inequalities in birth weight need to consider differences in adiposity and the possibility that increasing birth weight in South Asian infants might inadvertently worsen health by increasing relative adiposity.

Background: Despite advances in the treatment of childhood cancer, some children continue to die from their disease. This study aimed to assess the impact of specialist paediatric palliative care services (SPPCSs) on the number of hospital admissions in children who subsequently died from cancer in Yorkshire, UK., Methods: An extract of patients aged 0-19 years from the Yorkshire Specialist Register of Cancer in Children and Young People (YSRCCYP) diagnosed from 1990 to 2009 were linked to inpatient hospital episodes data and a SPPCS database. Deaths were included if they occurred before 31 August 2011. Differences in hospital admission patterns were assessed using negative binomial regression and presented as incidence rate ratios (IRRs)., Results: Of 2508 children on the YSRCCYP, 657 (26%) had died by the censoring date. A total of 211 children had been referred to the local SPPCS, of whom 182 (86%) had subsequently died. Referral to SPPCS was associated with a significant reduction in the rate of planned hospital admissions (IRR=0.60, 95% CI 0.43-0.85). Central nervous system tumours showed significant decreases for all planned and emergency admissions compared with all other diagnostic groups., Conclusion: Referral to SPPCS significantly reduced the number of planned hospital admissions for children and young people with cancer before their death, which are often integral to paediatric oncology treatment regimens. Overall, our findings show that SPPCS have a role in reducing hospital admissions during end of life care of paediatric cancer patients with potential personal, social and economic benefits.

Background: Progressive neuromuscular disease in children is life limiting and these children and young people would benefit from palliative care services, but data are limited on the number and demography of these children., Aim: To describe the clinical and demographic profile of children referred to a Children's hospice in the UK with progressive neuromuscular disease., Setting/participants: All children and young people with progressive neuromuscular disorders referred to Martin House Children's Hospice between 1987 and 2010., Design: Retrospective cohort study., Results: 300 children with progressive neuromuscular disease were referred to the hospice. Seventy percent (210) of these children had Duchenne Muscular Dystrophy, 22% (67) had Spinal Muscular Atrophy (34 with Type I) and 8% had other neuromuscular diseases. Numbers of referrals have not significantly increased over the last 15 years, although an increasing number come from a South Asian background (from 4% to 32%) and a higher number of children have conditions other than Duchenne Muscular Dystrophy. A total of 55.3% (166) of all referrals came from areas of the highest deprivation. Survival patterns varied by diagnostic group, but ethnicity and deprivation were not associated with survival in these children., Conclusions: The profile of children with progressive neuromuscular conditions who were referred for palliative care has changed over the last 20 years, with a different spectrum of underlying diagnoses and a greater number from a South Asian background. The higher than expected proportion of children living in areas of high deprivation has been consistent over time.

The general relationship between cancers of the upper aerodigestive tract (UADT) and alcohol drinking is established. Nevertheless, it is uncertain whether different types of alcoholic beverages (wine, beer and liquor) carry different UADT cancer risks. Our study included 2,001 UADT cancer cases and 2,125 controls from 14 centres in 10 European countries. All cases were histologically or cytologically confirmed squamous cell carcinomas. Controls were frequency matched by sex, age and centre. Logistic regression models were used to estimate odds ratios (OR) and 95 % confidence intervals (95 %CI) adjusted for age, sex, centre, education level, vegetable and fruit intake, tobacco smoking and alcohol drinking, where appropriate. Risk of beverage-specific alcohol consumption were calculated among 'pure drinker' who consumed one beverage type exclusively, among 'predominant drinkers' who consumed one beverage type to more than 66 % and among 'mixed drinkers' who consumed more than one beverage type to similar proportions. Compared to never drinkers and adjusted for cumulative alcohol consumption, the OR and 95 %CI for wine, beer and liquor drinking, respectively, were 1.24 (0.86, 1.78), 1.54 (1.05, 2.27) and 0.94 (0.53, 1.64) among 'pure drinkers' (p value for heterogeneity across beverage types = 0.306), 1.05 (0.76,1.47), 1.25 (0.87,1.79) and 1.43 (0.95, 2.16) among 'predominant drinkers' (p value = 0.456), and 1.09 (0.79, 1.50), 1.20 (0.88, 1.63) and 1.12 (0.82, 1.53) among 'mixed drinkers' (p value = 0.889). Risk of UADT cancer increased with increasing consumption of all three alcohol beverage types. Our findings underscore the strong and comparable carcinogenic effect of ethanol in wine, beer and liquor on organs of the UADT.

Background: The aetiology of bone cancers is poorly understood. This study examined geographical patterning in incidence of primary bone cancers diagnosed in 0-49 year olds in Great Britain during 1980-2005 to provide information on factors linked with disease development. We investigated putative associations with deprivation and population density., Methods: Data on osteosarcoma and Ewing sarcoma were obtained from national population-based registries. Negative binomial regression was used to examine the relationship between incidence rates and the Townsend deprivation score (and its component variables) and small-area population density., Results: The study analyzed 2566 osteosarcoma and 1650 Ewing sarcoma cases. For females with osteosarcoma, statistically significant decreased risk was associated with higher levels of deprivation (relative risk [RR] per unit increase in deprivation score = 0.969; 95% confidence interval [CI] 0.946-0.993). For all Ewing sarcoma combined, statistically significant decreased risk was associated with greater area-level population density and higher levels of non-car ownership (RR per person per hectare increase = 0.984; 95% CI 0.976-0.993, RR per 1% increase in non-car ownership = 0.994; 95% CI 0.991-0.998)., Conclusions: Higher incidence of osteosarcoma was observed for females in areas with lower deprivation levels indicating increased risk is linked to some aspect of affluent living. Higher incidence of Ewing sarcoma occurred in areas of low population density and where more people owned cars, both characteristic of rural environments. The study adds substantially to evidence associating Ewing sarcoma risk with rural environmental exposures. Putative risk factors include agricultural exposures, such as pesticides and zoonotic agents.

The availability of resource (staffing and services) in all 21 paediatric diabetes services in Yorkshire and Humber Strategic Health Authority, UK was surveyed and this information was combined with demographic and clinical data on 2683 children and young people with diabetes (aged 0-23 years) to assess whether level of resource was associated with glycaemic control (mean HbA1c %). Multilevel modelling and graphical techniques were used to analyse the relationship between resource and outcome for paediatric diabetes services. No services achieved all resource recommendations based on National Institute for Health and Clinical Excellence guidelines, but there was no direct association between level of resource and glycaemic control after controlling for deprivation, age and duration of diabetes. Transitional care, nurse caseload and access to specialist services are not adequately resourced but variation in outcome between services is not accounted for by level of resource.

We investigated the association between occupational history and upper aerodigestive tract (UADT) cancer risk in the ARCAGE European case-control study. The study included 1,851 patients with incident cancer of the oral cavity, oropharynx, hypopharynx, larynx or esophagus and 1,949 controls. We estimated odds ratios (OR) and 95% confidence intervals (CI) for ever employment in 283 occupations and 172 industries, adjusting for smoking and alcohol. Men (1,457 cases) and women (394 cases) were analyzed separately and we incorporated a semi-Bayes adjustment approach for multiple comparisons. Among men, we found increased risks for occupational categories previously reported to be associated with at least one type of UADT cancer, including painters (OR = 1.74, 95% CI: 1.01-3.00), bricklayers (1.58, 1.05-2.37), workers employed in the erection of roofs and frames (2.62, 1.08-6.36), reinforced concreters (3.46, 1.11-10.8), dockers (2.91, 1.05-8.05) and workers employed in the construction of roads (3.03, 1.23-7.46), general construction of buildings (1.44, 1.12-1.85) and cargo handling (2.60, 1.17-5.75). With the exception of the first three categories, risks both increased when restricting to long duration of employment and remained elevated after semi-Bayes adjustment. Increased risks were also found for loggers (3.56, 1.20-10.5) and cattle and dairy farming (3.60, 1.15-11.2). Among women, there was no clear evidence of increased risks of UADT cancer in association with occupations or industrial activities. This study provides evidence of an association between some occupational categories and UADT cancer risk among men. The most consistent findings, also supported by previous studies, were obtained for specific workers employed in the construction industry., (Copyright © 2011 UICC.)

Background: Life-limiting conditions (LLCs) describe diseases with no reasonable hope of cure that will ultimately be fatal. For children with these diseases, palliative care services should be available but few data are available to estimate the burden of these conditions., Methods: Children (0-19 years) with LLCs were identified within an English Hospital Episode Statistics dataset (2000/2001-2009/2010) by applying a customized coding framework of the International Classification of Diseases, 10th Revision, disease codes. Prevalence per 10 000 population (0-19 years) was calculated by age, diagnostic group, ethnicity, deprivation, and region for each year., Results: The Hospital Episode Statistics extract contained 175 286 individuals with 1 or more LLCs of which congenital anomalies were the most common (31%). Prevalence increased over 10 years from 25 to 32 per 10 000 population. Prevalence in the South Asian (48 per 10 000); black (42 per 10 000); and Chinese, mixed, and "other" (31 per 10 000) populations were statistically significantly higher compared with the white population (27 per 10 000). Prevalence shows an inverse J-shaped relationship with 5 categories of deprivation, with the highest prevalence in the most deprived areas and the lowest in the second least deprived., Conclusions: In 2010, the prevalence of LLCs in children in England was double the previously reported estimates and had increased annually in all areas over the past decade. This clearly identifies an escalating need for specialist pediatric palliative care services. When planning services for these increasing needs, the excess prevalence in ethnic minority groups, especially in deprived areas, needs to be considered.

Background: The study aimed to investigate the role of medical history (skin warts, Candida albicans, herpetic lesions, heartburn, regurgitation) and medication use (for heartburn; for regurgitation; aspirin) in the aetiology of upper aerodigestive tract (UADT) cancer., Methods: A multicentre (10 European countries) case-control study [Alcohol-Related CAncers and GEnetic susceptibility (ARCAGE) project]., Results: There were 1779 cases of UADT cancer and 1993 controls. History of warts or C. albicans infection was associated with a reduced risk [odds ratio (OR) 0.80, 95% confidence interval (CI) 0.68-0.94 and OR 0.73, 95% CI 0.60-0.89, respectively] but there was no association with herpetic lesions, heartburn, regurgitation or medication for related symptoms. Regurgitation was associated with an increased risk for cancer of the oesophagus (OR 1.47, 95% CI 0.98-2.21). Regular aspirin use was not associated with risk of UADT cancer overall but was associated with a reduced risk for cancer of oesophagus (OR 0.51, 95% CI 0.28-0.96), hypopharynx (OR 0.53, 95% CI 0.28-1.02) and larynx (OR 0.74, 95% CI 0.54-1.01)., Conclusions: A history of some infections appears to be a marker for decreased risk of UADT cancer. The role of medical history and medication use varied by UADT subsites with aspirin use associated with a decreased risk of oesophageal cancer and suggestive of a decreased risk of hypopharyngeal and laryngeal cancers.

Patient outcome from glioma may be influenced by germline variation. Considering the importance of DNA repair in cancer biology as well as in response to treatment, we studied the relationship between 1458 SNPs, which captured the majority of the common genetic variation in 136 DNA repair genes, in 138 glioblastoma samples from Sweden and Denmark. We confirmed our findings in an independent cohort of 121 glioblastoma patients from the UK. Our analysis revealed nine SNPs annotating MSH2, RAD51L1 and RECQL4 that were significantly (p < 0.05) associated with glioblastoma survival.

Introduction: Several studies have shown differences in survival trends between ethnic groups across adults with cancer in the UK. It is unclear whether these differences exist exclusively in the older adult population or whether they begin to emerge in children and young adults., Methods: Subjects (n=3534) diagnosed with cancer under 30 years of age in Yorkshire between 1990 and 2005 were analysed. Differences in survival rates for diagnostic subgroups were estimated by ethnic group (south Asian or not) using Kaplan-Meier estimation and Cox regression., Results: When compared to non-south Asians (all other ethnic groups excluding south Asians) a significant increased risk of death was seen for south Asians with leukaemia (hazard ratio (HR)=1.75; 95% confidence interval (CI)=1.11-2.76) and lymphoma (HR=2.05; 95% CI=1.09-3.87), whereas south Asians with solid tumours other than central nervous system tumours had a significantly reduced risk of death(HR=0.50; 95% CI=0.28-0.89). This was independent of socioeconomic deprivation., Conclusion: We found evidence of poorer survival outcomes for south Asians compared to non-south Asian children and young adults with leukaemia and lymphoma, but better outcomes for south Asian children and young adults with other solid tumours. This needs to be explained, and carefully addressed in the on-going development of cancer services., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: We specifically tested the aetiological hypothesis that a factor influencing geographical or temporal heterogeneity of childhood central nervous system (CNS) tumour incidence was related to exposure to a transient environmental agent., Methods: Information was extracted on individuals aged 0-14 years, diagnosed with a CNS tumour between the 1st January 1974 and 31st December 2006 from the Yorkshire Specialist Register of Cancer in Children and Young People. Ordnance Survey eight-digit grid references were allocated to each case with respect to addresses at the time of birth and the time of diagnosis, locating each address to within 0.1 km. The following diagnostic groups were specified a priori for analysis: ependymoma; astrocytoma; primitive neuroectodermal tumours (PNETs); other gliomas; total CNS tumours. We applied the K-function method for testing global space-time clustering using fixed geographical distance thresholds. Tests were repeated using variable nearest neighbour (NN) thresholds., Results: There was statistically significant global space-time clustering for PNETs only, based on time and place of diagnosis (P = 0.03 and 0.01 using the fixed geographical distance and the variable NN threshold versions of the K-function method respectively)., Conclusions: There was some evidence for a transient environmental component to the aetiology of PNETs. However, a possible role for chance cannot be excluded.

Deoxynivalenol (DON) is a ubiquitous contaminant of cereal crops in temperate regions of the world. It causes growth faltering and immune suppression in animals. Limited information is available on DON exposure in UK subpopulations. The objective of this study was to provide DON exposure assessment in a subset of pregnant women scheduled for an elective caesarean in a large multi-ethnic mother/infant birth cohort from Bradford, UK. Women aged 16-44 years (n = 85) provided a urine sample for DON analysis in the last trimester of pregnancy, and concurrently completed a food-frequency questionnaire (FFQ). The urinary DON biomarker was detected in all measured samples (geometric mean (GM) = 10.3 ng DON mg(-1) creatinine, range = 0.5-116.7 ng mg(-1)). Levels were higher in women classified as South Asian in origin (GM: 15.2 ng mg(-1); 95% CI = 10.7-21.5 ng mg(-1)) compared with non-South Asians (GM = 8.6 ng mg(-1); 95% CI = 6.6-11.8 ng mg(-1)), p = 0.02). Estimated DON intake from FFQ data and typical levels of DON contamination of food suggest that this was mainly due to higher levels of exposure from bread, particularly daily intake of DON from chapattis in South Asians (estimated mean = 2.4 µg day(-1); 95% CI = 1.2, 3.7 µg day(-1)) compared with non-South Asians (estimated mean = 0.2 µg day(-1); 95% CI = 0-0.4 µg day(-1)), p < 0.001. This is the first biomarker demonstration of DON exposure in pregnant women, and several urinary DON levels were the highest ever recorded in any study. A larger survey within this birth cohort is warranted to investigate any potential risk to mothers and their babies, from DON exposure during pregnancy.

High dependency care (HDC) is a level of care situated between intensive care and usual ward care with its delivery being independent of location. Inadequate definition makes it problematic to determine the number of children receiving HDC, to identify their care setting and therefore to undertake service planning. We aimed to estimate the volume of hospital inpatient HDC in a geographically defined population using a customised measurement tool in four types of paediatric hospital services (1) tertiary specialist wards, (2) tertiary paediatric intensive care units, (3) district general hospitals (DGHs) general wards and (4) wards at a major acute general hospital. A region-wide prospective cohort study during 2005 collected data to develop a 36-item HDC measurement tool, which then identified children receiving HDC by day and night. The cohort identified 1,763 children as receiving HDC during an admission to 1 of 36 hospital wards in 14 hospitals. HDC was delivered during 9,077 shift periods of 12 h or 4,538 bed days. The volume of care and patient profiles varied by hospital type, within hospital by ward type and by age and season. Tertiary specialist wards and ICUs provided 72% of HDC, with the remainder delivered at the DGHs and the major acute general hospital. The volume of admissions to tertiary specialist wards showed little seasonality and children tended to be older (26% were aged 10-15 years). By comparison, admissions to DGHs were younger with an excess during the winter months. This is the first UK study to quantify HDC from empirical data encompassing all hospital and ward types within a large clinical network. A lack of HDC-designated beds across the region resulted in HDC delivery on all types of hospital wards. The study size and representativeness makes the estimated number of HDC bed days per head of population likely to reflect the wider UK population.

Objective: To determine where children die following discharge from paediatric intensive care units (PICUs) in Great Britain and to investigate if this varies by discharge to palliative care., Design: National cohort of PICU admissions linked to Office of National Statistics death certificate data., Setting: 31 PICUs in Great Britain., Participants: A cohort of 35 383 children admitted to PICUs between 1 November 2002 until 25 January 2007., Main Outcome Measures: Place of death by palliative care discharge status., Results: 2346 (6.6%) deaths occurred after discharge during the study period, which is more than 10 times the normal child population mortality of 6.0 per 1000. Discharge to palliative care resulted in fewer deaths in hospital (44.1%) (compared to non-palliative care discharges (77.7%)), a greater proportion of deaths were at home (33.3% compared to non-palliative discharges 16.1%) and in a hospice (22.5% compared to non-palliative discharges 5.8%)., Conclusions: Children referred to palliative care services at discharge from PICU are more likely to die in the community (home or hospice) than children not referred to palliative care.

Aims: Incidence of Type 1 diabetes in children is increasing worldwide. Earlier studies suggest that UK south Asian immigrants develop similar rates to the overall UK population, although incidence is lower in their country of origin. This study examines incidence rate trends of childhood Type 1 diabetes in Yorkshire 1978-2007, focusing on differences between south Asians and non-south Asians., Methods: Data from the population-based Yorkshire Register of Diabetes in Children and Young People were used to estimate incidence (per 100,000 childhood population < 15 years per year) of Type 1 diabetes, stratified by sex, age and ethnicity validated using two name-recognition programs. Age-sex standardized rates were calculated for 1978-2007 and assessed by ethnic-group and deprivation for 1990-2007. We used Poisson regression to assess incidence trends and predict rates until 2020., Results: From 1978-2007, 3912 children were diagnosed. Overall incidence was 18.1 per 100,000 childhood population (< 15 years) per year (95% CI17.6-18.7) and increased significantly over time: 13.2 (1978-1987) to 17.3 (1988-1997) to 24.2 (1998-2007). Average annual percentage change was 2.8% (2.5-3.2). Incidence for non-south Asians (21.5; 20.7-22.4) was significantly higher than for south Asians (14.7; 12.4-17.1). Average annual percentage change increased significantly over 18 years (1990-2007) in non-south Asians (3.4%; 2.7-4.2) compared with a non-significant rise of 1.5% (-1.5 to 4.6) in south Asians. Deprivation score did not affect overall incidence., Conclusions: Type 1 diabetes incidence rose almost uniformly for non-south Asians, but not for south Asians, contrary to previous studies. Overall rates are predicted to rise by 52% from 2007 to 2020 to 39.0 per 100,000 per year., (© 2011 The Authors. Diabetic Medicine © 2011 Diabetes UK.)

The purpose of this study was to explore the variation in DNA repair genes in adults with WHO grade II and III gliomas and their relationship to patient survival. We analysed a total of 1,458 tagging single-nucleotide polymorphisms (SNPs) that were selected to cover DNA repair genes, in 81 grade II and grade III gliomas samples, collected in Sweden and Denmark. The statistically significant genetic variants from the first dataset (P < 0.05) were taken forward for confirmation in a second dataset of 72 grade II and III gliomas from northern UK. In this dataset, eight gene variants mapping to five different DNA repair genes (ATM, NEIL1, NEIL2, ERCC6 and RPA4) which were associated with survival. Finally, these eight genetic variants were adjusted for treatment, malignancy grade, patient age and gender, leaving one variant, rs4253079, mapped to ERCC6, with a significant association to survival (OR 0.184, 95% CI 0.054-0.63, P = 0.007). We suggest a possible novel association between rs4253079 and survival in this group of patients with low-grade and anaplastic gliomas that needs confirmation in larger datasets.

Tobacco and alcohol are major risk factors for upper aerodigestive tract (UADT) cancer and significant variation is observed in UADT cancer rates across Europe. We have estimated the proportion of UADT cancer burden explained by tobacco and alcohol and how this varies with the incidence rates across Europe, cancer sub-site, gender and age. This should help estimate the minimum residual burden of other risk factors to UADT cancer, including human papillomavirus. We analysed 1981 UADT cancer cases and 1993 controls from the ARCAGE multicentre study. We estimated the population attributable risk (PAR) of tobacco alone, alcohol alone and their joint effect. Tobacco and alcohol together explained 73% of UADT cancer burden of which nearly 29% was explained by smoking alone, less than 1% due to alcohol on its own and 44% by the joint effect of tobacco and alcohol. Tobacco and alcohol together explained a larger proportion of hypopharyngeal/laryngeal cancer (PAR=85%) than oropharyngeal (PAR=74%), esophageal (PAR=67%) and oral cancer (PAR=61%). Tobacco and alcohol together explain only about half of the total UADT cancer burden among women. Geographically, tobacco and alcohol explained a larger proportion of UADT cancer in central (PAR=84%) than southern (PAR=72%) and western Europe (PAR=67%). While the majority of the UADT cancers in Europe are due to tobacco or the joint effect of tobacco and alcohol, our results support a significant role for other risk factors in particular, for oral and oropharyngeal cancers and also for UADT cancers in southern and western Europe., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Despite extensive research on the topic, glioma etiology remains largely unknown. Exploration of potential interactions between single-nucleotide polymorphisms (SNP) of immune genes is a promising new area of glioma research. The case-only study design is a powerful and efficient design for exploring possible multiplicative interactions between factors that are independent of one another. The purpose of our study was to use this exploratory design to identify potential pair wise SNP-SNP interactions from genes involved in several different immune-related pathways for investigation in future studies., Methods: The study population consisted of two case groups: 1,224 histologic confirmed, non-Hispanic white glioma cases from the United States and a validation population of 634 glioma cases from the United Kingdom. Polytomous logistic regression, in which one SNP was coded as the outcome and the other SNP was included as the exposure, was utilized to calculate the ORs of the likelihood of cases simultaneously having the variant alleles of two different SNPs. Potential interactions were examined only between SNPs located in different genes or chromosomes., Results: Using this data mining strategy, we found 396 significant SNP-SNP interactions among polymorphisms of immune-related genes that were present in both the U.S. and U.K. study populations., Conclusion: This exploratory study was conducted for the purpose of hypothesis generation, and thus has provided several new hypotheses that can be tested using traditional case-control study designs to obtain estimates of risk., Impact: This is the first study, to our knowledge, to take this novel approach to identifying SNP-SNP interactions relevant to glioma etiology., (©2011 AACR.)

Cancer is the second most common cause of death in children and young people (0-19 years) accounting for 16.2% of deaths in England and Wales in 2005. Only 37.6% children and young people who died from cancer in Yorkshire were referred to Martin House Children's Hospice (MH) during the period 1990-2005. A significantly higher proportion with central nervous system tumours and a significantly lower than expected proportion with leukaemia or lymphoma were referred for palliative care. There is potential to increase the proportion of children and young people with cancer who are referred to specialist palliative care services., (Copyright © 2010 Wiley-Liss, Inc.)

Previous studies reported an inverse relationship between body mass index (BMI) and upper aerodigestive tract (UADT) cancers. Examining change in BMI over time may clarify these previous observations. We used data from 2,048 cases and 2,173 hospital- and population-based controls from ten European countries (alcohol-related cancers and genetic susceptibility in Europe study) to investigate the relationship with BMI and adult change in BMI on UADT cancer risk. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for associations between BMI at three time intervals and BMI change on UADT cancer development, adjusting for center, age, sex, education, fruit and vegetable intake, smoking and alcohol consumption. We found an inverse relationship between UADT cancers and BMI at time of interview and 2 years before interview. No association was found with BMI at 30 years of age. Regarding BMI change between age 30 and 2 years before interview, BMI decrease (BMI change <-5%) vs. BMI stability (-5% ≤ BMI change <5%) showed no overall association with UADT cancers (OR = 1.15; 95% CI = 0.89, 1.49). An increase in BMI (BMI change ≥+5%) was inversely associated with UADT cancers (OR = 0.74; 95% CI = 0.62, 0.89). BMI gain remained inversely associated across all subsites except for esophageal cancer. When stratified by smoking or by drinking, association with BMI gain was detected only in drinkers and smokers. In conclusion, BMI gain is inversely associated with UADT cancers. These findings may be influenced by smoking and/or drinking behaviors and/or the development of preclinical UADT cancers and should be corroborated in studies of a prospective nature., (Copyright © 2010 UICC.)

Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls. The 19 top-ranked variants were investigated further in an additional 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies participating in the INHANCE consortium. Five common variants presented evidence for significant association in the combined analysis (p ≤ 5 × 10⁻⁷). Two novel variants were identified, a 4q21 variant (rs1494961, p = 1×10⁻⁸) located near DNA repair related genes HEL308 and FAM175A (or Abraxas) and a 12q24 variant (rs4767364, p =2 × 10⁻⁸) located in an extended linkage disequilibrium region that contains multiple genes including the aldehyde dehydrogenase 2 (ALDH2) gene. Three remaining variants are located in the ADH gene cluster and were identified previously in a candidate gene study involving some of these samples. The association between these three variants and UADT cancers was independently replicated in 5,092 UADT cancer cases and 6,794 controls non-overlapping samples presented here (rs1573496-ADH7, p = 5 × 10⁻⁸); rs1229984-ADH1B, p = 7 × 10⁻⁹; and rs698-ADH1C, p = 0.02). These results implicate two variants at 4q21 and 12q24 and further highlight three ADH variants in UADT cancer susceptibility., Competing Interests: The authors have declared that no competing interests exist.

Objective: To investigate incidence trends of all diabetes types in all children and young people and in the south Asian subpopulation., Research Design and Methods: Annual incidence per 100,000 and time trends (1991-2006) were analyzed for 2,889 individuals aged 0-29 years diagnosed with diabetes while resident in West Yorkshire, U.K., Results: Diagnoses comprised type 1 (83%), type 2 (12%), maturity-onset diabetes of the young (0.7%), "J"-type/other (0.1%), and uncertain/unclassified (4%). There was a lower incidence of type 1 and a threefold excess of type 2 in south Asians compared with non-south Asians. Type 1 incidence leveled out and type 2 increased after the first south Asian case of type 2 was diagnosed in 1999. Type 2 and unclassified diabetes incidence rose in all population subgroups., Conclusions: The burden of diabetes increased over time for both ethnic groups, with a significant excess of type 2 diabetes in south Asians. The rising incidence of type 1 diabetes in south Asians attenuated as type 2 diabetes increased after 1999.

Background: Teenage and young adult (TYA) patient care can fall into gaps between adult and children's services. Increasingly UK TYA multi-disciplinary teams manage germ cell tumors (GCT) in locally agreed collaborations and age ranges. Patterns of care are changing rapidly. However, between disciplines protocols define different assessment and management in GCT. We aimed to document changes in incidence, treatment, and survival since 1990, to record the baseline to which future trends can be compared., Procedure: Details were extracted from the UK population-based Yorkshire Specialist Cancer Register on 237 TYA aged 13-24 years diagnosed with a GCT between 1990 and 2004, followed-up until 2009. Incidence and survival patterns were assessed using Poisson and Cox regression., Results: Testicular (n = 190; 80%) and ovarian (n = 22; 9%) GCT were the most common malignancies, and 90% of GCT occurred aged 17-24 years. The overall incidence rate was 26.9 per million person years. Rates increased significantly by 4.0% (95% CI: 1.0-7.1%) per year on average. The most common treatment modality was surgery combined with chemotherapy (49%). Initial treatment changed significantly over time (P = 0.003) and by age (P = 0.005). There were significant differences in the management of stage 1 testicular tumors by age. Among 13- to 16-year olds, 56% were treated exclusively in adult departments. Five-year survival rates were 93-95% for gonadal GCT, and 70-75% for other sites. Survival did not differ by age (P = 0.65) or period (P = 0.41)., Conclusions: The age-related differences observed in the approach to GCT treatment suggest a collaborative approach to the models of care among TYA is required., (Copyright © 2010 Wiley-Liss, Inc.)

Objective: To determine the relationship between the risk of type 1 diabetes (T1D) and daily intake of drinking water and dietary components, including nitrate, nitrite, and nitrosamines, during the year prior to diagnosis., Methods: Controls (n = 105) were matched by age at diagnosis and sex to T1D cases (n = 57) newly diagnosed during 2001-2004. Food consumption was assessed using a food frequency questionnaire. Locally available samples of foods were tested for nitrate, nitrite, and nitrosamine concentrations. Water consumption was determined through an additional questionnaire, and water samples were taken from homes and tested for routine chemical components, including nitrate., Results: After controlling for age, age, sex, and daily energy intake, nitrate intake from food sources showed a non-significant positive trend (odds ratios and 95% confidence intervals for quartiles = 1.00, 1.63 (0.58, 4.63), 1.71 (0.54, 5.40), 3.02 (0.78, 11.74); p for trend = 0.13). Nitrite and nitrosamine intake were not related to T1D risk (p for trend = 0.77 and 0.81, respectively). When food and water components were combined, zinc and calcium intakes were marginally and inversely related to T1D risk (p for trend = 0.07 and 0.06, respectively). After further model adjustment of possible confounders and significant risk factors, an increased intake of caffeine marginally increased the risk of T1D (p = 0.07)., Conclusion: Dietary components from both food and water sources may influence the risk of developing T1D in young persons.

Early life infection has been implicated in the aetiology of many chronic diseases, most often through proxy measures. Data on ten infectious symptoms were collected by parental questionnaire when children were 6 months old as part of the Avon Longitudinal Study of Parents and Children, United Kingdom. A latent class analysis was used to identify patterns of infection and their relationship to five factors commonly used as proxies: sex, other children in the home, maternal smoking, breastfeeding and maternal education. A total of 10,032 singleton children were included in the analysis. Five classes were identified with differing infectious disease patterns and children were assigned to the class for which they had a highest probability of membership based on their infectious symptom profile: 'general infection' (n = 1,252, 12.5%), 'gastrointestinal' (n = 1,902, 19.0%), 'mild respiratory' (n = 3,560, 35.5%), 'colds/ear ache' (n = 462, 4.6%) and 'healthy' (n = 2,856, 28.5%). Females had a reduced risk of being in all infectious classes, other children in the home were associated with an increased risk of being in the 'general infection', 'mild respiratory' or 'colds/ear ache' class. Breastfeeding reduced the risk of being in the 'general infection' and 'gastrointestinal' classes whereas maternal smoking increased the risk of membership. Higher maternal education was associated with an increased risk of being in the 'mild respiratory' group. Other children in the home had the greatest association with infectious class membership. Latent class analysis provided a flexible method of investigating the relationship between multiple symptoms and demographic and lifestyle factors.

Background: The incidence of cancers of the upper aerodigestive tract (UADT) is increasing throughout the world. To date the increases have been proportionally greatest among young people. Several reports have suggested that they often do not have a history of tobacco smoking or heavy alcohol consumption., Objective: To determine the contribution of lifestyle factors to the etiology of UADT cancers occurring in those aged less than 50 years., Methods: A case-control study was conducted in 10 European countries. Cases were cancers of the oral cavity and pharynx, larynx and esophagus, and hospital or population controls were age and sex matched., Results: There were 356 cases younger than 50 years and 419 controls. Risk was strongly related to current smoking [odds ratio (OR) 5.5 95%; confidence interval (CI) (3.3, 9.2)], and risk increased with number of pack-years smoked. Risk was also related to alcohol consumption for both current (OR 1.8; 0.97, 3.3) and past (OR 3.4; 1.6, 7.4) drinkers, and risk increased with number of drink-years. Persons frequently consuming fruits and vegetables were at significantly reduced risk., Conclusions: Risk factors already identified as being important for UADT cancers in adults are also important influences on risk in younger adults. The implication of these results is that the public health message in preventing UADT cancers remains the same to young and old alike.

Background: No studies to date have demonstrated a clear association with breast cancer risk and dietary exposure to acrylamide., Methods: A 217-item food frequency questionnaire was used to estimate dietary acrylamide intake in 33,731 women aged 35-69 years from the UK Women's Cohort Study followed up for a median of 11 years., Results: In all, 1084 incident breast cancers occurred during follow-up. There was no evidence of an overall association between acrylamide intake and breast cancer (hazard ratio=1.08 per 10 μg day(-1), 95% CI: 0.98-1.18, P(trend)=0.1). There was a suggestion of a possible weak positive association between dietary acrylamide intake and premenopausal breast cancer after adjustment for potential confounders (hazard ratio=1.2, 95% CI: 1.0-1.3, P(trend)=0.008). There was no suggestion of any association for postmenopausal breast cancer (hazard ratio=1.0, 95% CI: 0.9-1.1, P(trend)=0.99)., Conclusions: There is no evidence of an association between dietary acrylamide intake and breast cancer. A weak association may exist with premenopausal breast cancer, but requires further investigation.

Background: Few studies have examined epidemiological differences between ethnic groups for children and young adults with cancer., Methods: Subjects aged 0-29 years, diagnosed between 1990 and 2005 in the former Yorkshire Regional Health Authority, were included in the analysis. Ethnicity (south Asian or not) was assigned using name analysis program and Hospital Episode Statistics data. Differences in incidence (per 1,000,000 person-years) rates and trends were analysed using joinpoint and Poisson regression analysis., Results: Overall cancer incidence was similar for south Asians (12.1, 95% CI: 10.7-13.5; n=275) and non-south Asians (12.6, 95% CI: 12.2-13.1; n=3259). Annual incidence rates increased significantly by 1.9% per year on average (95% CI: 1.2-2.6%), especially for south Asians (7.0%; 95% CI: 4.2-9.9%)., Conclusion: If present trends continue, the higher rate of increase seen among south Asians aged 0-29 years in Yorkshire will result in three times higher cancer incidence than non-south Asians by 2020.

To determine whether inherited variations in immune function single-nucleotide polymorphisms (SNPs), genes or pathways affect glioblastoma risk, we analyzed data from recent genome-wide association studies in conjunction with predefined immune function genes and pathways. Gene and pathway analyses were conducted on two independent data sets using 6629 SNPs in 911 genes on 17 immune pathways from 525 glioblastoma cases and 602 controls from the University of California, San Francisco (UCSF) and a subset of 6029 SNPs in 893 genes from 531 cases and 1782 controls from MD Anderson (MDA). To further assess consistency of SNP-level associations, we also compared data from the UK (266 cases and 2482 controls) and the Mayo Clinic (114 cases and 111 controls). Although three correlated epidermal growth factor receptor (EGFR) SNPs were consistently associated with glioblastoma in all four data sets (Mantel-Haenzel P values = 1 × 10⁻⁵ to 4 × 10⁻³), independent replication is required as genome-wide significance was not attained. In gene-level analyses, eight immune function genes were significantly (minP < 0.05) associated with glioblastoma; the IL-2RA (CD25) cytokine gene had the smallest minP values in both UCSF (minP = 0.01) and MDA (minP = 0.001) data sets. The IL-2RA receptor is found on the surface of regulatory T cells potentially contributing to immunosuppression characteristic of the glioblastoma microenvironment. In pathway correlation analyses, cytokine signaling and adhesion-extravasation-migration pathways showed similar associations with glioblastoma risk in both MDA and UCSF data sets. Our findings represent the first systematic description of immune genes and pathways that characterize glioblastoma risk.

We aim to describe the demographics and clinical characteristics of children discharged to palliative care from 31 paediatric intensive care units in Great Britain, using a cohort of admissions and discharges from the database of paediatric intensive care units (Paediatric Intensive Care Audit Network (PICANet)). The patients included in this study were children discharged alive from paediatric intensive care units (n = 68882) between 1 January 2004 and 31 December 2008. The main outcome measure was Odds Ratios for discharge of children from paediatric intensive care units to palliative care and their referral destination. We found that palliative care status was recorded for 68,090 live discharges from paediatric intensive care units, with 492 (0.7%) discharges to palliative care, a proportion that varied by Strategic Health Authority (range 0 to 1.1). The odds of discharge to palliative care were increased by expected probability of death (log odds of mortality) associated with an oncology, neurology or respiratory diagnosis. South Asian children referred to palliative care were less likely to receive this care in a hospice (OR 0.18, 95% CI 0.04,0.83) and more likely to receive it in a hospital setting (OR 2.57, 95% CI 1.16,5.71). We conclude that children admitted to paediatric intensive care units have a very low rate of discharge to palliative care. Specific demographic and clinical variables are associated with referral to palliative care.

Background: There is a paucity of recent epidemiological data on bone cancers. The aim of this study was to describe incidence and survival patterns for bone cancers diagnosed during 1981 - 2002., Methods: Cases aged 0 - 39 years (236 osteosarcomas, 166 Ewing sarcomas and 73 chondrosarcomas) were analysed using Poisson and Cox regressions., Results: Incidence rates (per million persons per year) for osteosarcoma were 2.5 at age 0 - 14 years; 4.5 at age 15 - 29 years and 1.0 at age 30 - 39 years. Similarly, for Ewing sarcoma the incidence rates were 2.2; 2.9; 0.4 and for chondrosarcoma rates were 0.1; 1.2; 1.8 respectively. Incidence of osteosarcoma increased at an average annual rate of 2.5% (95% CI 0.4 - 4.7; P = 0.02), but there was no change in incidence of Ewing sarcoma or chondrosarcoma. There was a marginally statistically significant improvement in survival for Ewing sarcoma (hazard ratio (HR) per annum = 0.97; 95% CI 0.94 - 1.00; P = 0.06), although patients aged 15 - 39 years (n = 93) had worse overall survival than those aged 0 - 14 (n = 73; HR = 1.46; 95% CI 0.98 - 2.17; P = 0.06). There was no significant improvement in osteosarcoma survival (HR per annum = 0.98; 95% CI 0.95 - 1.01; P = 0.18)., Conclusions: Reasons for poorer survival in Ewing sarcoma patients aged 15 - 39 years and failure to significantly improve survival for osteosarcoma patients requires further investigation.

The etiology of glioma is barely known. Epidemiologic studies have provided evidence for an inverse relation between glioma risk and allergic disease. Genome-wide association data have identified common genetic variants at 5p15.33 (rs2736100, TERT), 8q24.21 (rs4295627, CCDC26), 9p21.3 (rs4977756, CDKN2A-CDKN2B), 11q23.3 (rs498872, PHLDB1), and 20q13.33 (rs6010620, RTEL1) as determinants of glioma risk. The authors investigated whether there is interaction between the effects of allergy and these 5 variants on glioma risk. Data from 5 case-control studies carried out in Denmark, Finland, Sweden, and the United Kingdom (2000-2004) were used, totaling 1,029 cases and 1,668 controls. Risk was inversely associated with asthma, hay fever, eczema, and "any allergy," significantly for each factor except asthma, and was significantly positively associated with number of risk alleles for each of the 5 single nucleotide polymorphisms. There was interaction between asthma and rs498872 (greater protective effect of asthma with increasing number of risk alleles; per-allele interaction odds ratio (OR) = 0.65, P = 0.041), between "any allergy" and rs4977756 (smaller protective effect; interaction OR = 1.27, P = 0.047), and between "any allergy" and rs6010620 (greater protective effect; interaction OR = 0.70, P = 0.017). Case-only analyses provided further support for atopy interactions for rs4977756 and rs498872. This study provides evidence for possible gene-environment interactions in glioma development.

The aim of this study was to explore associations between social mobility and tumours of the upper aero-digestive tract (UADT), focussing on life-course transitions in social prestige (SP) based on occupational history. 1,796 cases diagnosed between 1993 and 2005 in ten European countries were compared with 1585 controls. SP was classified by the Standard International Occupational Prestige Scale (SIOPS) based on job histories. SIOPS was categorised in high (H), medium (M) and low (L). Time weighted average achieved and transitions between SP with nine trajectories: H --> H, H --> M, H --> L, M --> H, M --> M, M --> L, L --> H, L --> M and L --> L were analysed. Odds ratios (ORs) and 95%-confidence intervals [95%-CIs] were estimated with logistic regression models including age, consumption of fruits/vegetables, study centre, smoking and alcohol consumption. The adjusted OR for the lowest versus the highest of three categories (time weighted average of SP) was 1.28 [1.04-1.56]. The distance of SP widened between cases and controls during working life. The downward trajectory H --> L gave an OR of 1.71 [0.75-3.87] as compared to H --> H. Subjects with M --> M and L --> L trajectories ORs were also elevated relative to subjects with H --> H trajectories. The association between SP and UADT is not fully explained by confounding factors. Downward social trajectory during the life course may be an independent risk factor for UADT cancers.

Introduction: In the European Union, there are 180,000 new cases of upper aerodigestive tract (UADT) cancer cases per year--more than half of whom will die of the disease. Socioeconomic inequalities in UADT cancer incidence are recognised across Europe. We aimed to assess the components of socioeconomic risk both independently and through their influence on the known behavioural risk factors of smoking, alcohol consumption and diet., Patients and Methods: A multicentre case-control study with 2198 cases of UADT cancer and 2141 controls from hospital and population sources was undertaken involving 14 centres from 10 countries. Personal interviews collected information on demographics, lifetime occupation history, smoking, alcohol consumption and diet. Socioeconomic status was measured by education, occupational social class and unemployment. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed using unconditional logistic regression., Results: When controlling for age, sex and centre significantly increased risks for UADT cancer were observed for those with low versus high educational attainment OR=1.98 (95% CI 1.67, 2.36). Similarly, for occupational socioeconomic indicators--comparing the lowest versus highest International Socio-Economic Index (ISEI) quartile for the longest occupation gave OR=1.60 (1.28, 2.00); and for unemployment OR=1.64 (1.24, 2.17). Statistical significance remained for low education when adjusting for smoking, alcohol and diet behaviours OR=1.29 (1.06, 1.57) in the multivariate analysis. Inequalities were observed only among men but not among women and were greater among those in the British Isles and Eastern European countries than in Southern and Central/Northern European countries. Associations were broadly consistent for subsite and source of controls (hospital and community)., Conclusion: Socioeconomic inequalities for UADT cancers are only observed among men and are not totally explained by smoking, alcohol drinking and diet., (Copyright (c) 2009 Elsevier Ltd. All rights reserved.)

Objective: To provide new epidemiological evidence base of information on models of hospice care for children and young adults., Design: Retrospective cohort study of children referred to a hospice., Setting: Martin House Children's and Young Person's Hospice in Boston Spa, North Yorkshire, UK., Participants: All children who had been referred for care at Martin House Children's Hospice since it opened in August 1987, until May 2008., Main Outcome Measures: Demographic profiles and survival times overall and by diagnostic group classified by the Association of Children's Palliative Care (ACT) Diagnostic Categories, calculated using the Kaplan- Meier and log rank pair-wise methodology., Results: Over a 20-year period, 1554 children aged from birth to 19 years were referred to Martin House, of whom 89.5% (mean age 7.45 years) were accepted. The deprivation profile, referral source and distribution of diagnoses of these children have changed over time with recently increasing numbers of non-progressive disorders (ACT category 4). The ethnicity profile has changed with an increase in the numbers of South Asian children. The overall mean survival time was 5.6 years (95% CI 5.1 to 6.1) but this differed by ACT category. Diagnostic category was significantly associated with differing survival patterns., Conclusions: There are a disproportionate number of children from areas of higher deprivation being referred for palliative care services. There has been a recent increase in the number of children from South Asian families being referred to palliative care services in Yorkshire. Survival times for children and young people receiving care from a hospice can vary from hours and days to more than 20 years.

The complex associations between socioeconomic circumstances and risk for head and neck cancer are under-explored. We investigated components of social class and their relative influence on the risk of head and neck cancers by studying 103 patients (age range 24-80 years) who had been diagnosed with cancer of the head and neck between April 2002 and December 2004, and 91 controls who were randomly selected from general practitioners' lists. Information about occupation, education, smoking, and alcohol consumption was collected at personal interview. Socioeconomic circumstances were measured at an individual level (education, occupational social class, unemployment), and by area-based measures of deprivation. Odds ratios (OR) and 95% confidence intervals (CI) were computed using unconditional logistic regression and multivariate analyses. People living in the most deprived areas (OR=4.66, 95% CI 1.79-12.18); and those who were unemployed (OR=2.27, 95% CI 1.21-4.26) had a significantly higher risk of cancer than those with high levels of educational attainment (OR=0.17, 95% CI 0.05-0.58). Significance was lost for all measures of social class when adjustments were made for smoking and consumption of alcohol. Smoking was the only significant risk factor (OR=15.53, 95% CI 5.36-44.99) in the multivariate analysis. A high risk of head and neck cancer was consistently associated with poor socioeconomic circumstances, and there were strong links for specific components however smoking dominated the overall profile of risk. We propose a framework for future socioeconomic analyses., (Copyright 2009 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Introduction: Several important issues for the established association between tobacco smoking and upper aerodigestive tract (UADT) cancer risks include the associations with smoking by cancer subsite, by type of tobacco, and among never alcohol drinkers and the associations with involuntary smoking among nonsmokers. Our aim was to examine these specific issues in a large-scale case-control study in Europe., Methods: Analysis was done on 2,103 UADT squamous cell carcinoma cases and 2,221 controls in the Alcohol-Related Cancers and Genetic Susceptibility in Europe project, a multicenter case-control study in 10 European countries. Unconditional logistic regression was done to obtain odds ratios (OR) and 95% confidence intervals (95% CI)., Results: Compared with never tobacco smoking, current smoking was associated with UADT cancer risks (OR, 6.72; 95% CI, 5.45-8.30 for overall; OR, 5.83; 95% CI, 4.50-7.54 for oral cavity and oropharynx; OR, 12.19; 95% CI, 8.29-17.92 for hypopharynx and larynx; and OR, 4.17; 95% CI, 2.45-7.10 for esophagus). Among never drinkers, dose-response relationships with tobacco smoking pack-years were observed for hypopharyngeal and laryngeal cancers (P(trend) = 0.010) but not for oral cavity and oropharyngeal cancers (P(trend) = 0.282). Among never smokers, ever exposure to involuntary smoking was associated with an increased risk of UADT cancers (OR, 1.60; 95% CI, 1.04-2.46)., Conclusion: Our results corroborate that tobacco smoking may play a stronger role in the development of hypopharyngeal and laryngeal cancers than that of oral cavity and oropharyngeal cancers among never drinkers and that involuntary smoking is an important risk factor for UADT cancers. Public health interventions to reduce involuntary smoking exposure could help reduce UADT cancer incidence.

Background: Occupational exposure to extremely low frequency (ELF) magnetic fields (MF) in the UK general population is poorly documented., Aims: To assess levels of occupational exposure to ELF MF in the UK and evaluate the use of a rigid job-exposure matrix (JEM) to assign exposures to subjects in the UK Adult Brain Tumour Study (UKABTS)., Methods: Personal ELF MF measurements were carried out. Exposure traces were divided into occupational, travel and elsewhere periods, under differing exposure metrics. Exposure was classified by Standard Occupational Classification (2000), Standard Industrial Classification (1997), and a combined occupation-industry classification. Statistical analyses (mixed effects model) determined the contribution of occupational exposure to the 24 h cumulative exposure and the contribution of occupation and industry to total variance., Results: Data were obtained from 317 individuals, comprising UKABTS subjects (n = 192), occupational proxies for UKABTS subjects (n = 101) and "interest" readings (n = 24). 236 individuals provided occupational data covering 117 different occupations. Average exposure was significantly higher at work than at home. Elevated average occupational exposure was found for welding trades, printers, telephonists and filing and other records assistants. The discrimination of a rigid JEM based on occupation can be improved by linking the classification with industry and by the use of contextual information., Conclusions: This report substantially expands information on adult exposure to ELF MF in the UK. The accuracy of exposure assessments based solely on job codes is improved by linking with either industry code or contextual knowledge of equipment and of power lines or substations in the work environment.

B-cells influence T-cell reactivity by facilitating antigen presentation, but the role of autoantibody-secreting B-cells in regulating T-cell responses in Type 1 diabetes is poorly defined. The aims of this study were to characterise epitopes on the IA-2 autoantigen for three monoclonal antibodies from diabetic patients by amino acid substitutions of selected residues of IA-2, establish contributions of these epitopes to binding of serum antibodies in Type 1 diabetes and relate B- and T-cell responses to overlapping determinants on IA-2. The monoclonal antibodies recognised overlapping epitopes, with residues within the 831-860 region of IA-2 contributing to binding; substitution of Glu836 inhibited binding of all three antibodies. Monoclonal antibody Fab fragments and substitution of residues within the 831-836 region blocked serum antibody binding to an IA-2 643-937 construct. IL-10-secreting T-cells responding to peptides within the 831-860 region were detected by cytokine-specific ELISPOT in diabetic patients and responses to 841-860 peptide were associated with antibodies to the region of IA-2 recognised by the monoclonal antibodies. The study identifies a region of IA-2 frequently recognised by antibodies in Type 1 diabetes and demonstrates that these responses are associated with T-cells secreting IL-10 in response to a neighbouring determinant.

There is suggestive, but inconclusive, evidence that dietary factors may affect risk of cancers of the upper aerodigestive tract (UADT). In the context of the alcohol-related cancers and genetic susceptibility in Europe study, we have examined the association of dietary factors with UADT cancer risk. We have analyzed data from 2,304 patients with UADT cancer and 2,227 control subjects recruited in 14 centers in 10 European countries. Dietary data were collected through a semi-quantitative food frequency questionnaire that also assessed preferred temperature of hot beverages. Statistical analyses were conducted through multiple logistic regression controlling for potential confounding variables, including alcohol intake and smoking habits. Consumption of red meat (OR per increasing tertile = 1.14, 95% CI: 1.05-1.25), but not poultry, was significantly associated with increased UADT cancer risk and the association was somewhat stronger for esophageal cancer. Consumption of fruits (OR per increasing tertile = 0.68, 95% CI: 0.62-0.75) and vegetables (OR per increasing tertile = 0.73, 95% CI: 0.66-0.81) as well as of olive oil (OR for above versus below median = 0.78, 95% CI 0.67-0.90) and tea (OR for above versus below median = 0.83, 95% CI 0.69-0.98) were significantly associated with reduced risk of UADT cancer. There was no indication that an increase in tea or coffee temperature was associated with increased risk of UADT overall or cancer of the esophagus; in fact, the association was, if anything, inverse. In conclusion, the results of this large multicentric study indicate that diet plays an important role in the etiology of UADT cancer.