Minouk J Schoemaker

Publications of Minouk J Schoemaker

• Body Mass Index, Exercise, and Other Lifestyle Factors in Relation to Age at Natural Menopause: Analyses From the Breakthrough Generations Study.

  Authors: Danielle H Morris, Michael E Jones, Minouk J Schoemaker, Emily McFadden, Alan Ashworth, Anthony J Swerdlow

  American journal of epidemiology. 04/2012;

  The authors examined the effect of women's lifestyles on the timing of natural menopause using data from a cross-sectional questionnaire used in the United Kingdom-based Breakthrough GenerationsThe authors examined the effect of women's lifestyles on the timing of natural menopause using data from a cross-sectional questionnaire used in the United Kingdom-based Breakthrough Generations Study in 2003-2011. The analyses included 50,678 women (21,511 who had experienced a natural menopause) who were 40-98 years of age at study entry and did not have a history of breast cancer. Cox competing risks proportional hazards models were fitted to examine the relation of age at natural menopause to lifestyle and anthropometric factors. Results were adjusted for age at reporting, smoking status at menopause, parity, and body mass index at age 40 years, as appropriate. All P values were 2-sided. High adult weight (P(trend) < 0.001), high body mass index (P(trend) < 0.001), weight gain between the ages of 20 and 40 years (P(trend) = 0.01), not smoking (P < 0.001), increased alcohol consumption (P(trend) < 0.001), regular strenuous exercise (P < 0.01), and not being a vegetarian (P < 0.001) were associated with older age at menopause. Neither height nor history of an eating disorder was associated with menopausal age. These findings show the importance of lifestyle factors in determining menopausal age.

• Familial concordance for height and its components: analyses from the breakthrough generations study.

  Authors: Danielle H Morris, Michael E Jones, Minouk J Schoemaker, Alan Ashworth, Anthony J Swerdlow

  American journal of human biology : the official journal of the Human Biology Council. 11/2011; 24(1):22-7.

  To assess familial resemblance for height, arm span, and components of these, and differences between concordance for short and tall heights. We examined whether female relatives were similar for sixTo assess familial resemblance for height, arm span, and components of these, and differences between concordance for short and tall heights. We examined whether female relatives were similar for six anthropometric measurements (height, arm span, leg, trunk and arm length, and leg:trunk length ratio). Subjects were 31,622 related individuals aged 16-102 yr participating in the UK Breakthrough Generations Study. Height and arm span were self-reported, limb and trunk length were measured in a subset (N = 508) by study investigators, and paternal height was reported by the daughter. Data were analyzed using correlations and Poisson regression. Correlation coefficients within families were 0.4 for height, 0.3 for arm span, and 0.5 for leg length, trunk length, leg:trunk ratio, and arm length. Women had a relative risk (RR) of being short (i.e., in the lowest height quintile) of 2.3 (95% confidence interval [CI] = 2.1-2.5) if their mother was short, 2.1 (95% CI = 1.9-2.3) if their father was short, and 3.7 (95% CI = 3.4-4.0) if both parents were short. RRs of being tall (i.e., in the highest height quintile) were 2.3 (95% CI = 2.1-2.5), 2.4 (95% CI = 2.2-2.6), and 4.4 (95% CI = 4.1-4.8) if their mother, father or both were tall, respectively. We have shown, for the first time, that leg:trunk length ratio and arm length aggregate within families. Concordance seemed to be stronger for tall than short heights.

• 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.

• Chromosome 7p11.2 (EGFR) variation influences glioma risk.

  Authors: Marc Sanson, Fay J Hosking, Sanjay Shete, Diana Zelenika, Sara E Dobbins, Yussanne Ma, Victor Enciso-Mora, Ahmed Idbaih, Jean-Yves Delattre, Khe Hoang-Xuan [......] Stefan Schreiber, Andre Franke, Susanne Moebus, Lewin Eisele, Asta Försti, Kari Hemminki, Mark Lathrop, Melissa Bondy, Richard S Houlston, Matthias Simon

  Human molecular genetics. 07/2011; 20(14):2897-904.

  While gliomas are the most common primary brain tumors, their etiology is largely unknown. To identify novel risk loci for glioma, we conducted genome-wide association (GWA) analysis of twoWhile gliomas are the most common primary brain tumors, their etiology is largely unknown. To identify novel risk loci for glioma, we conducted genome-wide association (GWA) analysis of two case-control series from France and Germany (2269 cases and 2500 controls). Pooling these data with previously reported UK and US GWA studies provided data on 4147 glioma cases and 7435 controls genotyped for 424 460 common tagging single-nucleotide polymorphisms. Using these data, we demonstrate two statistically independent associations between glioma and rs11979158 and rs2252586, at 7p11.2 which encompasses the EGFR gene (population-corrected statistics, P(c) = 7.72 × 10(-8) and 2.09 × 10(-8), respectively). Both associations were independent of tumor subtype, and were independent of EGFR amplification, p16INK4a deletion and IDH1 mutation status in tumors; compatible with driver effects of the variants on glioma development. These findings show that variation in 7p11.2 is a determinant of inherited glioma risk.

• Secular trends in age at menarche in women in the UK born 1908-93: results from the Breakthrough Generations Study.

  Authors: Danielle H Morris, Michael E Jones, Minouk J Schoemaker, Alan Ashworth, Anthony J Swerdlow

  Paediatric and perinatal epidemiology. 07/2011; 25(4):394-400.

  Menarcheal age decreased over time in Western countries until cohorts born in the mid-20th century. It then stabilised, but limited data are available for recent cohorts. Menarche data were collectedMenarcheal age decreased over time in Western countries until cohorts born in the mid-20th century. It then stabilised, but limited data are available for recent cohorts. Menarche data were collected retrospectively by questionnaire in 2003-10 from 94,170 women who were participating in the Breakthrough Generations Study, aged 16-98 years, born 1908-93 and resident in the UK. Average menarcheal age declined from women born in 1908-19 (mean=13.5 years) to those born in 1945-49 (mean=12.6 years). It was then stable for several birth cohorts, but resumed its downward trend in recent cohorts (mean=12.3 years in 1990-93 cohort). Trends differed between socio-economic groups, but the recent decline was present in each group. In conclusion, menarcheal age appears to have decreased again in recent cohorts after a period of stabilisation.

• A novel approach to exploring potential interactions among single-nucleotide polymorphisms of inflammation genes in gliomagenesis: an exploratory case-only study.

  Authors: E Susan Amirian, Michael E Scheurer, Yanhong Liu, Anthony M D'Amelio, Richard S Houlston, Carol J Etzel, Sanjay Shete, Anthony J Swerdlow, Minouk J Schoemaker, Patricia A McKinney, Sarah J Fleming, Kenneth R Muir, Artitaya Lophatananon, Melissa L Bondy

  Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 07/2011; 20(8):1683-9.

  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 promisingDespite 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. 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. 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. 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. This is the first study, to our knowledge, to take this novel approach to identifying SNP-SNP interactions relevant to glioma etiology.

• Familial concordance for age at menarche: analyses from the Breakthrough Generations Study.

  Authors: Danielle H Morris, Michael E Jones, Minouk J Schoemaker, Alan Ashworth, Anthony J Swerdlow

  Paediatric and perinatal epidemiology. 05/2011; 25(3):306-11.

  Age at menarche is correlated within families, but estimates of the heritability of menarcheal age have a wide range (0.45-0.95). We examined the familial resemblance for age at menarche and theAge at menarche is correlated within families, but estimates of the heritability of menarcheal age have a wide range (0.45-0.95). We examined the familial resemblance for age at menarche and the extent to which this is due to genetic and shared environmental factors. Between 2003 and 2010 data were retrospectively collected by questionnaire from participants within the UK-based Breakthrough Generations Study. These analyses included 25,970 female participants aged 16-98 with at least one female relative who was also a study participant. A woman's menarche was significantly delayed for each yearly increase in the menarcheal age of her monozygotic twin (average increase = 7.2 months, P < 0.001), dizygotic twin (average increase = 3.0 months, P = 0.03), older sister (average increase = 3.3 months, P < 0.001), mother (average increase = 3.4 months, P < 0.001), maternal grandmother (average increase = 1.5 months, P = 0.04), maternal aunt (average increase = 1.4 months, P < 0.001) and paternal aunt (average increase = 3.0 months, P < 0.001). There was not a significant association between the menarcheal ages of half-sister pairs or of paternal grandmother-granddaughter pairs, based on small numbers. Heritability was estimated as 0.57 [95% confidence interval 0.53, 0.61]. Shared environmental factors did not have an effect in the model. In conclusion, approximately half of the variation in age at menarche was attributable to additive genetic effects with the remainder attributable to non-shared environmental effects.

• Familial concordance for age at natural menopause: results from the Breakthrough Generations Study.

  Authors: Danielle H Morris, Michael E Jones, Minouk J Schoemaker, Alan Ashworth, Anthony J Swerdlow

  Menopause (New York, N.Y.). 04/2011; 18(9):956-61.

  Existing estimates of the heritability of menopause age have a wide range. Furthermore, few studies have analyzed to what extent familial similarities might reflect shared environment, rather thanExisting estimates of the heritability of menopause age have a wide range. Furthermore, few studies have analyzed to what extent familial similarities might reflect shared environment, rather than shared genes. We therefore analyzed familial concordance for age at natural menopause and the effects of shared genetic and environmental factors on this concordance. Participants were 2,060 individuals comprising first-degree relatives, aged 31 to 90 years, and participating in the UK Breakthrough Generations Study. Menopause data were collected using a self-administered questionnaire and analyzed using logistic regression and variance-components models. Women were at an increased risk of early menopause (≤45 y) if their mother (odds ratio, 6.2; P < 0.001) or non-twin sister (odds ratio, 5.5; P < 0.001) had had an early menopause. Likewise, women had an increased risk of late menopause (≥54 y) if their relative had had a late menopause (mother: odds ratio, 6.1; P < 0.01; non-twin sister: odds ratio, 2.3; P < 0.001). Estimated heritability was 41.6% (P < 0.01), with an additional 13.6% (P = 0.02) of the variation in menopause age attributed to environmental factors shared by sisters. We confirm that early menopause aggregates within families and show, for the first time, that there is also strong familial concordance for late menopause. Both genes and shared environment were the source of variation in menopause age. Past heritability estimates have not accounted for shared environment, and thus, the effect of genetic variants on menopause age may previously have been overestimated.

• 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.

• Common genetic variants are significant risk factors for early menopause: results from the Breakthrough Generations Study.

  Authors: Anna Murray, Claire E Bennett, John R B Perry, Michael N Weedon, Patricia A Jacobs, Danielle H Morris, Nicholas Orr, Minouk J Schoemaker, Michael Jones, Alan Ashworth, Anthony J Swerdlow

  Human molecular genetics. 10/2010; 20(1):186-92.

  Women become infertile approximately 10 years before menopause, and as more women delay childbirth into their 30s, the number of women who experience infertility is likely to increase. Tests thatWomen become infertile approximately 10 years before menopause, and as more women delay childbirth into their 30s, the number of women who experience infertility is likely to increase. Tests that predict the timing of menopause would allow women to make informed reproductive decisions. Current predictors are only effective just prior to menopause, and there are no long-range indicators. Age at menopause and early menopause (EM) are highly heritable, suggesting a genetic aetiology. Recent genome-wide scans have identified four loci associated with variation in the age of normal menopause (40-60 years). We aimed to determine whether theses loci are also risk factors for EM. We tested the four menopause-associated genetic variants in a cohort of approximately 2000 women with menopause≤45 years from the Breakthrough Generations Study (BGS). All four variants significantly increased the odds of having EM. Comparing the 4.5% of individuals with the lowest number of risk alleles (two or three) with the 3.0% with the highest number (eight risk alleles), the odds ratio was 4.1 (95% CI 2.4-7.1, P=4.0×10(-7)). In combination, the four variants discriminated EM cases with a receiver operator characteristic area under the curve of 0.6. Four common genetic variants identified by genome-wide association studies, had a significant impact on the odds of having EM in an independent cohort from the BGS. The discriminative power is still limited, but as more variants are discovered they may be useful for predicting reproductive lifespan.

• 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.

• Twinning in the offspring of parents with chronic radiation exposure from nuclear testing in Kazakhstan.

  Authors: Nadejda Y Mudie, Anthony J Swerdlow, Boris I Gusev, Minouk J Schoemaker, Ludmila M Pivina, Svetlana Chsherbakova, Almagul Mansarina, Susanne Bauer, Yuri Jakovlev, Kazbek N Apsalikov

  Radiation research. 06/2010; 173(6):829-36.

  The population of the Semipalatinsk region of Kazakhstan was chronically exposed to radioactive fallout from above-ground nuclear tests conducted during 1949-1956 by the Soviet Union. We investigatedThe population of the Semipalatinsk region of Kazakhstan was chronically exposed to radioactive fallout from above-ground nuclear tests conducted during 1949-1956 by the Soviet Union. We investigated the effect of radiation exposure and other factors on risks of twinning overall and of same- and different-sex twinning and hence estimated dizygotic and monozygotic twinning rates in 11,605 deliveries around Semipalatinsk, 141 of which were twin, to 3992 mothers exposed to fallout during 1949-1956. Overall, the same-sex twinning rate was 7.85 [95% confidence interval (CI): 6.24, 9.47] per 1000 and the opposite-sex twinning rate was 4.45 (95% CI: 3.23, 5.67). Twinning rates did not differ significantly between radiation exposure categories, parental age at main radiation exposure, or year of birth. Different-sex, but not same-sex, twinning increased with maternal age (P(trend) = 0.04) but not with other demographic factors and was increased soon after radiation exposure [OR = 4.08 (95% CI: 1.11, 15.07)] for births occurring within 5 years compared with more than 20 years after exposure; this effect was similar in villages with low and high radiation exposure, however, so interpretation is uncertain.

• 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.

• A comprehensive study of the association between the EGFR and ERBB2 genes and glioma risk.

  Authors: Ulrika Andersson, Judith Schwartzbaum, Fredrik Wiklund, Sara Sjöström, Yanhong Liu, Spyros Tsavachidis, Anders Ahlbom, Anssi Auvinen, Helle Collatz-Laier, Maria Feychting, Christoffer Johansen, Anne Kiuru, Stefan Lönn, Minouk J Schoemaker, Anthony J Swerdlow, Roger Henriksson, Melissa Bondy, Beatrice Melin

  Acta oncologica (Stockholm, Sweden). 05/2010; 49(6):767-75.

  Glioma is the most common type of adult brain tumor and glioblastoma, its most aggressive form, has a dismal prognosis. Receptor tyrosine kinases such as the epidermal growth factor receptor (EGFR,Glioma is the most common type of adult brain tumor and glioblastoma, its most aggressive form, has a dismal prognosis. Receptor tyrosine kinases such as the epidermal growth factor receptor (EGFR, ERBB2, ERBB3, ERBB4) family, and the vascular endothelial growth factor receptor (VEGFR), play a central role in tumor progression. We investigated the genetic variants of EGFR, ERBB2, VEGFR and their ligands, EGF and VEGF on glioma and glioblastoma risk. In addition, we evaluated the association of genetic variants of a newly discovered family of genes known to interact with EGFR: LRIG2 and LRIG3 with glioma and glioblastoma risk. Methods. We analyzed 191 tag single nucleotide polymorphisms (SNPs) capturing all common genetic variation of EGF, EGFR, ERBB2, LRIG2, LRIG3, VEGF and VEGFR2 genes. Material from four case-control studies with 725 glioma patients (329 of who were glioblastoma patients) and their 1 610 controls was used. Haplotype analyses were conducted using SAS/Genetics software. Results. Fourteen of the SNPs were significantly associated with glioma risk at p< 0.05, and 17 of the SNPs were significantly associated with glioblastoma risk at p< 0.05. In addition, we found that one EGFR haplotype was related to increased glioblastoma risk at p=0.009, Odds Ratio [OR] = 1.67 (95% confidence interval (CI): 1.14, 2.45). The Bonferroni correction made all p-values non-significant. One SNP, rs4947986 next to the intron/exon boundary of exon 7 in EGFR, was validated in an independent data set of 713 glioblastoma and 2 236 controls, [OR] = 1.42 (95% CI: 1.06,1.91). Discussion. Previous studies show that regulation of the EGFR pathway plays a role in glioma progression but the present study is the first to find that certain genotypes of the EGFR gene may be related to glioblastoma risk. Further studies are required to reinvestigate these findings and evaluate the functional significance.

• Risk factors for pituitary tumors: a case-control study.

  Authors: Minouk J Schoemaker, Anthony J Swerdlow

  Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 06/2009; 18(5):1492-500.

  Pituitary gland tumors are usually benign but are associated with substantial morbidity. Their etiology is largely unknown. We conducted a population-based case-control study of potential riskPituitary gland tumors are usually benign but are associated with substantial morbidity. Their etiology is largely unknown. We conducted a population-based case-control study of potential risk factors for pituitary tumors in Southeast England. Information on medical and reproductive history, female sex hormones, and cigarette smoking was collected by personal interview from 299 cases and 630 controls aged 18 to 59 years. Tumor risk was reduced in subjects reporting a past diagnosis of hay fever [odds ratio (OR), 0.7; 95% confidence interval (CI), 0.5-1.0] but not asthma or eczema. Risk was raised in women who were postmenopausal 1 year before diagnosis (OR, 3.2; 95% CI, 1.6-6.2), especially if menopause was surgically induced (OR, 6.7; 95% CI, 2.2-19.9) or occurred under age 40 years (OR, 7.5; 95% CI, 2.6-21.4). This effect remained when evaluating menopausal status 10 years before diagnosis. There was no association with parity overall, but risk was increased for first childbirth under age 20 years compared with nulliparity (OR, 3.4; 95% CI, 1.4-8.4). No significant association was observed with ever use of oral contraceptives or hormone replacement therapy, nor with cigarette smoking, past head injury, past diagnosis with epilepsy, or birth characteristics, except for an inverse association of risk with maternal age. This study suggests a raised risk of pituitary tumors in relation to surgically induced menopause, early postmenopausal age, and young age at childbirth, and possibly a reduced risk with hay fever and increasing maternal age. Reasons for these associations need further investigation, but some associations might be due to hormonal effects of an undiagnosed pituitary tumor.

• Mortality in women with Turner syndrome in Great Britain: a national cohort study.

  Authors: Minouk J Schoemaker, Anthony J Swerdlow, Craig D Higgins, Alan F Wright, Patricia A Jacobs

  The Journal of clinical endocrinology and metabolism. 10/2008;

  Context: Turner syndrome is characterised by complete or partial X chromosome monosomy. It is associated with substantial morbidity, but mortality risks and causes of death are not well described.Context: Turner syndrome is characterised by complete or partial X chromosome monosomy. It is associated with substantial morbidity, but mortality risks and causes of death are not well described. Objectives: To investigate mortality and causes of death in women with Turner syndrome. Design and setting: We constructed a cohort of women diagnosed with Turner syndrome at almost all cytogenetic centres in Great Britain and followed them for mortality. Patients: 3,439 women diagnosed between 1959-2002, followed to end 2006. Outcome measures: Standardised mortality ratios (SMRs) and absolute excess risks (AERs). Results: In total, 296 deaths occurred. Mortality was significantly raised overall (SMR=3.0 [95% CI: 2.7-3.4]) and was raised for nearly all major causes of death. Circulatory disease accounted for 41% of excess mortality, with greatest SMRs for aortic aneurysm (SMR=23.6, 95% CI: 13.8-37.8) and aortic valve disease (SMR=17.9, 95% CI: 4.9-46.0), but SMRs were also raised for other circulatory conditions. Other major contributors to raised mortality included congenital cardiac anomalies, diabetes, epilepsy, liver disease, non-infectious enteritis and colitis, renal and ureteric disease and pneumonia. Absolute excess risks of death were considerably greater at older than younger ages. Conclusions: Mortality in women with Turner syndrome is threefold higher than in the general population, is raised for almost all major causes of death, and is raised at all ages, with the greatest excess mortality in older adulthood. These risks need consideration in follow-up and counselling of patients, and add to reasons for continued follow-up and preventive measures in adult, not just paediatric, care.

• Reproductive Factors and Risk of Meningioma and Glioma.

  Authors: Annette Wigertz, Stefan Lönn, Per Hall, Anssi Auvinen, Helle Collatz Christensen, Christoffer Johansen, Lars Klæboe, Tiina Salminen, Minouk J Schoemaker, Anthony J Swerdlow, Tore Tynes, Maria Feychting

  Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 10/2008; 17(10):2663-2670.

  Female sex hormones have previously been suggested as possible risk factors for brain tumors, but published studies have reported conflicting results. We conducted a population-based case-controlFemale sex hormones have previously been suggested as possible risk factors for brain tumors, but published studies have reported conflicting results. We conducted a population-based case-control study of glioma (n = 626) and meningioma (n = 906) cases and randomly selected controls stratified on age and geographic region (n = 1,774) in Denmark, Finland, Norway, Sweden, and the United Kingdom. Unconditional logistic regression was used to estimate odds ratios (OR) for glioma and meningioma in relation to reproductive factors. A decreased glioma risk was associated with ever-pregnancy compared with never-pregnancy [OR, 0.8; 95% confidence interval (95% CI), 0.6-1.0]. Meningioma risk among women ages <50 years was increased in relation to number of pregnancies leading to a live birth (OR, 1.8; 95% CI: 1.1-2.8 for giving birth to 3 children compared with nulliparous women; P(trend) among parous women = 0.01). This relation was not found for older women. Breast-feeding among parous women increased the glioma risk (OR, 2.2; 95% CI, 1.3-3.9 for breast-feeding 36 months or more compared with breast-feeding 3 months or less). Menopausal status and age at menopause were not associated with meningioma or glioma risk. Our findings imply that reproductive hormones may influence the occurrence of meningioma and glioma. (Cancer Epidemiol Biomarkers Prev 2008;17(10):2663-70).

• Cancer incidence in women with Turner syndrome in Great Britain: a national cohort study.

  Authors: Minouk J Schoemaker, Anthony J Swerdlow, Craig D Higgins, Alan F Wright, Patricia A Jacobs

  The lancet oncology. 04/2008; 9(3):239-46.

  BACKGROUND: Turner syndrome, one of the most common cytogenetic abnormalities, is characterised by complete or partial X-chromosome monosomy. Cancer risks in women with Turner syndrome have not beenBACKGROUND: Turner syndrome, one of the most common cytogenetic abnormalities, is characterised by complete or partial X-chromosome monosomy. Cancer risks in women with Turner syndrome have not been clearly established. We aimed to compare the risk of cancer in women with this syndrome with that of the general population. METHODS: We formed a national cohort of 3425 women who were cytogenetically diagnosed with Turner syndrome in Great Britain between 1959 and 2002. Identifying information for these patients was sent to the National Health Service Central Register (NHSCR) for England and Wales and to the NHSCR for Scotland. Individuals who were identified on this register were followed-up for cancer incidence. Standardised incidence ratios (SIRs) and 95% CIs were calculated on the basis of the number of cancers observed compared with that expected based on national incidence rates. Cumulative risk estimates were obtained by use of the Kaplan-Meier method. FINDINGS: A total of 58,299 person-years were accrued during the study, with a mean of 17.0 years (SD 8.6) follow-up per patient. 73 malignancies other than non-melanoma skin cancer occurred (SIR 0.9 [95% CI 0.7-1.2]). Risks were significantly increased for tumours of the CNS (n=13; 4.3 [2.3-7.4]), especially for meningioma (n=7; 12.0 [4.8-24.8]) and childhood brain tumours (n=3; 10.3 [2.1-30.1]), and for cancers of the bladder and urethra (n=5; 4.0 [1.3-9.2]) and eye (n=2; 10.5 [1.3-37.9]), compared with the general population. However, the risk of breast cancer was significantly decreased (n=10; 0.3 [0.2-0.6]). The SIR for cutaneous melanoma was 2.2 (95% CI 1.0-4.4; n=8), and one of the ocular cancers was a melanoma. The risk of corpus uteri cancer was significantly increased at ages 15-44 years (n=3; 8.0 [1.6-23.2]). During follow-up, five women, all with a Y-chromosome lineage, developed gonadoblastoma of the ovary, corresponding to a cumulative risk of 7.9% (95% CI 3.1-19.0) by age 25 years in this group. INTERPRETATION: This study shows that, in addition to having an increased risk of gonadoblastoma, women with Turner syndrome seem to be at increased risk for meningioma and childhood brain tumours, and possibly bladder cancer, melanoma, and corpus uteri cancer, but are at a decreased risk for breast cancer. Reasons for these risks might relate to genetic and hormonal factors or to the effects of hormonal treatments given to women with Turner syndrome.

• Mortality risks in patients with constitutional autosomal chromosome deletions in Britain: a cohort study.

  Authors: Anthony J Swerdlow, Minouk J Schoemaker, Craig D Higgins, Alan F Wright, Patricia A Jacobs

  Human genetics. 03/2008; 123(2):215-24.

  Constitutional chromosome deletions result in wide ranging morbidity and often fatality. Information about risks and causes of death in these patients is important for counselling, and may illuminateConstitutional chromosome deletions result in wide ranging morbidity and often fatality. Information about risks and causes of death in these patients is important for counselling, and may illuminate the functions of the part of the chromosome deleted. There have been no cohort studies analysing mortality risks in persons with specific deletions compared with general population rates. We therefore conducted a cohort study following cause-specific mortality in 2,561 patients with autosomal chromosome deletions diagnosed by light microscopy or fluorescence in situ hybridisation at cytogenetic laboratories across Britain, 1965-2002. The commonest deletions were of 22q (544 patients), 15q (460) and 7q (210) and the least common 19q (0) and 20q (2). The prevalence of visible deletions of different chromosome arms was significantly inversely correlated with gene density of the arm (p < 0.001). Mortality was 11-fold raised in the cohort compared with the general population (standardised mortality ratio = 11.4 (95% confidence interval 10.0-12.8)), was significantly raised for each deletion with > or = 25 subjects in the study, and had a lower confidence limit > 10 for deletions of 1p, 1q, 3p, 4p, 5q and 22q. Overall, 29% of deaths were due to congenital anomalies; significantly raised mortality occurred also from many other causes, varying by chromosome and arm of deletion. The data imply that viability of foetuses with visible chromosome deletions may be inversely related to gene density, and that all visible and fluorescence in situ hybridisation-detectable deletions lead to much raised mortality, but the extent and causes of mortality vary according to the specific deletion.

• An international case-control study of interleukin-4Ralpha, interleukin-13, and cyclooxygenase-2 polymorphisms and glioblastoma risk.

  Authors: Judith A Schwartzbaum, Anders Ahlbom, Stefan Lönn, Beatrice Malmer, Annette Wigertz, Anssi Auvinen, Anthony J Brookes, Helle Collatz Christensen, Roger Henriksson, Christoffer Johansen, Tina Salminen, Minouk J Schoemaker, Anthony J Swerdlow, Waldemar Debinski, Maria Feychting

  Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 12/2007; 16(11):2448-54.

  Previous studies found that allergies are inversely related to risk of glioma. In an earlier publication, using data from a Swedish case-control study, Schwartzbaum et al. report an inverse relationPrevious studies found that allergies are inversely related to risk of glioma. In an earlier publication, using data from a Swedish case-control study, Schwartzbaum et al. report an inverse relation between risk of glioblastoma and four single nucleotide polymorphisms (SNP) on two genes [interleukin (IL)-4Ralpha, IL-13] that are associated with allergies. In addition, recent studies suggest that IL-4 and IL-13 induce cyclooxygenase-2 (COX-2) to resolve brain inflammation. To see whether previous Swedish results (110 cases, 430 controls) would be replicated, we estimated the association between glioblastoma and two IL-4Ralpha (rs1805015, rs1801275) and two IL-13 (rs20541, rs1800925) SNPs and their haplotypes and one COX-2 SNP (-765GC) using additional English, Danish, and Finnish data (217 cases, 1,171 controls). Among general population controls, we evaluated associations between these haplotypes, the COX-2 SNP, and self-reported allergies. Our data did not support our original observations relating individual IL-4Ralpha, IL-13, or COX-2 SNPs to glioblastoma risk. However, the T-G IL-4Ralpha haplotype was associated with glioblastoma risk (odds ratio, 2.26; 95% confidence interval, 1.13-4.52) and there was a suggestion of an inverse relation between this haplotype and hayfever prevalence among controls (odds ratio, 0.38; 95% confidence interval, 0.14-1.03). The lack of support for a link between four IL-4Ralpha and IL-13 SNPs and glioblastoma may reflect the absence of associations or may result from uncontrolled confounding by haplotypes related both to those that we examined and glioblastoma. Nonetheless, the association between the T-G IL-4Ralpha haplotype and glioblastoma risk may indicate a role of immune factors in glioblastoma development.