Sarah J Hepworth

Publications of Sarah J Hepworth

• Common variation at 10p12.31 near MLLT10 influences meningioma risk.

  Authors: Sara E Dobbins, Peter Broderick, Beatrice Melin, Maria Feychting, Christoffer Johansen, Ulrika Andersson, Thomas Brännström, Johannes Schramm, Bianca Olver, Amy Lloyd [......] Per Hoffmann, Thomas W Mühleisen, Markus M Nöthen, Susanne Moebus, Lewin Eisele, Michael Kosteljanetz, Kenneth Muir, Anthony Swerdlow, Matthias Simon, Richard S Houlston

  Nature genetics. 07/2011; 43(9):825-7.

  To identify susceptibility loci for meningioma, we conducted a genome-wide association study of 859 affected individuals (cases) and 704 controls with validation in two independent sample setsTo identify susceptibility loci for meningioma, we conducted a genome-wide association study of 859 affected individuals (cases) and 704 controls with validation in two independent sample sets totaling 774 cases and 1,764 controls. We identified a new susceptibility locus for meningioma at 10p12.31 (MLLT10, rs11012732, odds ratio = 1.46, P(combined) = 1.88 × 10(-14)). This finding advances our understanding of the genetic basis of meningioma development.

• Allergy and glioma risk: test of association by genotype.

  Authors: Sara E Dobbins, Fay J Hosking, Sanjay Shete, Georgina Armstrong, Anthony Swerdlow, Yanhong Liu, Robert Yu, Ching Lau, Minouk J Schoemaker, Sarah J Hepworth, Kenneth Muir, Melissa Bondy, Richard S Houlston

  International journal of cancer. Journal international du cancer. 04/2011; 128(7):1736-40.

  Although epidemiological studies have suggested an association between atopy and glioma risk, these observations have been based on self-reporting of allergic conditions raising the possibility thatAlthough epidemiological studies have suggested an association between atopy and glioma risk, these observations have been based on self-reporting of allergic conditions raising the possibility that associations may be noncausal and arise as a consequence of bias, reverse causation or other artifacts. Genetic information provides an alternative approach to investigate the relationship avoiding such biases. We analyzed 1,878 glioma cases and 3,670 controls for variants at 2q12, 5q12.1, 11q13 and 17q21 that are associated with asthma or eczema risk at p < 5.0 × 10(-7) . The SNP rs7216389, which tags the 3' flanking region of ORMDL3 at 17q21 and has been associated with childhood asthma, was correlated with increased glioma risk (OR = 1.10; 95% CI: 1.01-1.19). These data provide evidence for a correlation between asthma susceptibility and glioma risk and illustrate the value of using genetics as an investigative tool for developing etiological hypotheses.

• Early life patterns of common infection: a latent class analysis.

  Authors: Sarah J Hepworth, Graham R Law, Debbie A Lawlor, Patricia A McKinney

  European journal of epidemiology. 10/2010; 25(12):875-83.

  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 whenEarly 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.

• Inherited variation in immune genes and pathways and glioblastoma risk.

  Authors: Judith A Schwartzbaum, Yuanyuan Xiao, Yanhong Liu, Spyros Tsavachidis, Mitchel S Berger, Melissa L Bondy, Jeffrey S Chang, Susan M Chang, Paul A Decker, Bo Ding [......] Michael Prados, Terri Rice, Lindsay B Robertson, Minouk J Schoemaker, Sanjay Shete, Anthony J Swerdlow, Joe L Wiemels, John K Wiencke, Ping Yang, Margaret R Wrensch

  Carcinogenesis. 10/2010; 31(10):1770-7.

  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 associationTo 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.

• Interaction between 5 genetic variants and allergy in glioma risk.

  Authors: Minouk J Schoemaker, Lindsay Robertson, Annette Wigertz, Michael E Jones, Fay J Hosking, Maria Feychting, Stefan Lönn, Patricia A McKinney, Sarah J Hepworth, Kenneth R Muir, Anssi Auvinen, Tiina Salminen, Anne Kiuru, Christoffer Johansen, Richard S Houlston, Anthony J Swerdlow

  American journal of epidemiology. 06/2010; 171(11):1165-73.

  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 identifiedThe 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.

• Genome-wide association study identifies five susceptibility loci for glioma.

  Authors: Sanjay Shete, Fay J Hosking, Lindsay B Robertson, Sara E Dobbins, Marc Sanson, Beatrice Malmer, Matthias Simon, Yannick Marie, Blandine Boisselier, Jean-Yves Delattre [......] Yanhong Liu, Xiangjun Gu, Robert Yu, Ching Lau, Minouk Schoemaker, Kenneth Muir, Anthony Swerdlow, Mark Lathrop, Melissa Bondy, Richard S Houlston

  Nature genetics. 09/2009; 41(8):899-904.

  To identify risk variants for glioma, we conducted a meta-analysis of two genome-wide association studies by genotyping 550K tagging SNPs in a total of 1,878 cases and 3,670 controls, with validationTo identify risk variants for glioma, we conducted a meta-analysis of two genome-wide association studies by genotyping 550K tagging SNPs in a total of 1,878 cases and 3,670 controls, with validation in three additional independent series totaling 2,545 cases and 2,953 controls. We identified five risk loci for glioma at 5p15.33 (rs2736100, TERT; P = 1.50 x 10(-17)), 8q24.21 (rs4295627, CCDC26; P = 2.34 x 10(-18)), 9p21.3 (rs4977756, CDKN2A-CDKN2B; P = 7.24 x 10(-15)), 20q13.33 (rs6010620, RTEL1; P = 2.52 x 10(-12)) and 11q23.3 (rs498872, PHLDB1; P = 1.07 x 10(-8)). These data show that common low-penetrance susceptibility alleles contribute to the risk of developing glioma and provide insight into disease causation of this primary brain tumor.

• History of allergies and risk of glioma in adults.

  Authors: Minouk J Schoemaker, Anthony J Swerdlow, Sarah J Hepworth, Patricia A McKinney, Martie van Tongeren, Kenneth R Muir

  International journal of cancer. Journal international du cancer. 12/2006; 119(9):2165-72.

  Epidemiological studies have consistently reported an inverse association between a history of allergic disease and risk of glioma. The reason for this association is unclear, and there is a lack ofEpidemiological studies have consistently reported an inverse association between a history of allergic disease and risk of glioma. The reason for this association is unclear, and there is a lack of studies with the detail and size to explore the association in depth. We conducted a UK population-based case-control study with 965 glioma cases and 1,716 controls to investigate glioma risk in relation to allergic disease. Risk was reduced in subjects reporting a history of asthma (odds ratio (OR) = 0.71, 95% confidence interval (CI): 0.54-0.92), hay fever (OR = 0.73, 95% CI: 0.59-0.90), eczema (OR = 0.74, 95% CI: 0.56-0.97) and other allergies (OR = 0.65, 95% CI: 0.47-0.90). Risk was reduced for all the main histological groups. There was no significant trend of risk with age, at the onset of each condition, or the number of conditions reported. Risk reductions were strongest for asthma or hay fever with recent onset. Risk in asthmatic subjects was not related to frequency of use of antiasthmatic drugs, but was significantly reduced for use of antiallergenic medication among subjects with hay fever. The study showed an inverse association of glioma risk with allergic disease. Possible reasons for the association, as well as potential immunological aetiology, include confounding, bias and reverse causality.

• Mobile phone use and risk of glioma in adults: case-control study.

  Authors: Sarah J Hepworth, Minouk J Schoemaker, Kenneth R Muir, Anthony J Swerdlow, Martie J A van Tongeren, Patricia A McKinney

  BMJ (Clinical research ed.). 05/2006; 332(7546):883-7.

  OBJECTIVE: To investigate the risk of glioma in adults in relation to mobile phone use. DESIGN: Population based case-control study with collection of personal interview data. SETTING: Five areas ofOBJECTIVE: To investigate the risk of glioma in adults in relation to mobile phone use. DESIGN: Population based case-control study with collection of personal interview data. SETTING: Five areas of the United Kingdom. PARTICIPANTS: 966 people aged 18 to 69 years diagnosed with a glioma from 1 December 2000 to 29 February 2004 and 1716 controls randomly selected from general practitioner lists. MAIN OUTCOME MEASURES: Odds ratios for risk of glioma in relation to mobile phone use. RESULTS: The overall odds ratio for regular phone use was 0.94 (95% confidence interval 0.78 to 1.13). There was no relation for risk of glioma and time since first use, lifetime years of use, and cumulative number of calls and hours of use. A significant excess risk for reported phone use ipsilateral to the tumour (1.24, 1.02 to 1.52) was paralleled by a significant reduction in risk (0.75, 0.61 to 0.93) for contralateral use. CONCLUSIONS: Use of a mobile phone, either in the short or medium term, is not associated with an increased risk of glioma. This is consistent with most but not all published studies. The complementary positive and negative risks associated with ipsilateral and contralateral use of the phone in relation to the side of the tumour might be due to recall bias.

• Childhood leukaemias and CNS tumours: correlation of international incidence rates.

  Authors: Sarah J Hepworth, Richard G Feltbower, Patricia A McKinney

  European journal of cancer (Oxford, England : 1990). 04/2006; 42(4):509-13.

  Childhood leukaemia has a potential infectious aetiology whilst infections may also be linked to paediatric central nervous system (CNS) tumours. Using data from 29 countries we investigated theChildhood leukaemia has a potential infectious aetiology whilst infections may also be linked to paediatric central nervous system (CNS) tumours. Using data from 29 countries we investigated the correlation between international incidence rates of childhood leukaemia and CNS tumours, focusing on acute lymphoblastic leukaemia (ALL), astrocytoma and ependymoma-subtypes that are hypothesised to have an infectious aetiology. Relationships between incidence rates and national demographic factors were also examined using Pearson's correlation coefficient to quantify associations. Comparing two diagnostic categories of leukaemia with four groups of CNS tumours, a highly significant positive correlation was found between ALL and astrocytoma (r = 0.57, P = 0.002). Higher rates of ALL and CNS tumours were associated with increased affluence, with the strongest correlation for Gross Domestic Product per capita and CNS tumours (r = 0.70, P < 0.001). National incidence rates of childhood ALL and astrocytomas were highly correlated and this may reflect a common environmental cause whose origin may be infectious in nature. International incidence of ALL and CNS tumours were also correlated with economic related factors. Variation in levels of ascertainment may partially explain this, although childhood environmental exposures related to infections will also be affected by levels of affluence.

• Childhood cancer and power lines: results do not support causal role for electromagnetic fields.

  Authors: Sarah J Hepworth, Richard G Feltbower, Roger C Parslow, Patricia A McKinney

  BMJ (Clinical research ed.). 10/2005; 331(7517):634-5; discussion 636; author reply 636-7.