J. Schwartzbaum - Academia.edu (original) (raw)

Papers by J. Schwartzbaum

doi:10.5271/sjweh.1150 Cohort study of cancer risk among male and female shift workers

Neuro-Oncology, 2010

Allergies and the use of anti-inflammatory medication appear to be associated with reduced gliobl... more Allergies and the use of anti-inflammatory medication appear to be associated with reduced glioblastoma risk. However, these observations may merely reflect systemic immunosuppression induced by the tumor. To better understand the effect of this tumor on allergies and inflammation, we used CD133 mRNA expression as an indicator of tumor aggressiveness and systematically examined its relation to mRNA expression levels of 919 allergy-and inflammation-related genes in 142 glioblastoma tissue samples. We found that 69% of these genes are negatively correlated with CD133 expression including allergy-related (eg, interleukin [IL]-4R-a; Pearson correlation coefficient [r] 5 2 0.40; 95% confidence interval [CI] 5 2 0.53, 20.25) and immunoregulatory genes (eg, TGF-b1; r 5 2 0.35; 95% CI 5 2 0.49, 20.20). Exceptions to this negative trend include the proinflammatory cytokine IL-17-b (r 5 0.22; 95% CI 5 0.06, 0.37) and 2 IL-17 receptors. Also positively related to CD133 expression are NCAM-1 (r 5 0.45; 95% CI 5 0.31, 0.57) and PDGFR-a (r 5 0.45; 95% CI 5 0.30, 0.57). Previous literature suggests that NCAM-1 1 T cells infiltrate glioblastoma and may cause suppression of antitumor immunity, whereas PDGFR-a is involved in neurogenesis and amplified in glioblastoma. Ours is the first study to document downregulation of the majority of allergy-and inflammationrelated genes with glioblastoma progression. However, IL-17 and NCAM-1 may play proinflammatory and immunosuppressive roles, respectively, during the late stage of glioblastoma progression. Our findings suggest that immune function continues to change as the tumor progresses.

Journal of Neurology, Neurosurgery & Psychiatry, 2006

JNCI Journal of the National Cancer Institute, 2012

Background Previous nested case-control studies suggest that a prediagnostic biomarker of allergy... more Background Previous nested case-control studies suggest that a prediagnostic biomarker of allergy, IgE, is inversely associated with the risk of glioma, but these findings are inconsistent. The purpose of our study was to assess this association and determine how long before glioma diagnosis it may be observed. Methods We conducted a nested case-control study using serum specimens from the Janus Serum Bank cohort in Norway. Blood donors who were subsequently diagnosed with glioma (n = 594 case subjects), between January 1, 1974 to December 31, 2007, were matched with subjects without glioma (n = 1177 control subjects) for date of blood collection, 2-year age interval at blood collection, and sex. Respiratory allergen-specific and total IgE levels in the serum were measured using fluorescent assays. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression models stratified on sex and glioblastoma, the most common glioma subtype. Data were stratified on time from blood collection to tumor diagnosis to assess how long before glioma diagnosis the association could be observed. Results Among women, testing positive for allergen-specific IgE (>0.35 kU A /L) was associated with decreased risk of glioblastoma compared with testing negative (≤0.35 kU A /L; OR = 0.46, 95% CI = 0.23 to 0.93). Among both sexes combined, testing positive for total IgE (>100 kU/L) was associated with decreased risk of glioma compared with testing negative (≤100 kU/L; OR = 0.75, 95% CI = 0.56 to 0.99), and simultaneously testing positive for allergenspecific IgE and total IgE was associated with a borderline statistically significantly decreased risk of glioblastoma and glioma compared with simultaneously testing negative for these types of IgE. Testing positive for total IgE at least 20 years before diagnosis was associated with decreased risk of glioma compared with testing negative (OR = 0.54, 95% CI = 0.30 to 0.99). Conclusion An inverse association between IgE levels and risk of glioma was detected; the association was present at least 20 years before tumor diagnosis.

International Journal of Cancer, 2009

The consistently observed inverse relationship of allergic conditions with glioma risk and our pr... more The consistently observed inverse relationship of allergic conditions with glioma risk and our previous demonstration that IgE levels also were lower in glioma patients than controls suggest that atopic allergy may be related to a mechanism that inhibits or prevents glioma. We sought to extend these results with a new and larger series of patients (n=535 with questionnaire data; 393 with IgE measures) and controls (n=532 with questionnaire data; 470 with IgE measures). As expected, glioma cases were less likely than controls to report history of allergies (among self-reported cases, OR = 0.59, 95% CI: 0.41-0.85). IgE levels also were lower in glioma cases versus controls (OR per unit log IgE=0.89, 95% CI (0.82-0.98). However, this inverse relationship was only apparent among cases receiving temozolomide, a treatment which became part of the "standard of care" for glioblastoma patients during the study period. Among patients receiving temozolomide, IgE levels in cases whose blood samples were obtained within 30 days of diagnosis were slightly higher than controls, while IgE levels in cases whose blood sample was obtained >60 days after diagnosis were significantly lower than controls (OR = 0.80; 95% CI: 0.71-0.89). Thus, while our results robustly confirm the inverse association between allergy and glioma, the results for IgE are affected by temozolomide treatments which may have influenced IgE levels. These results have implications for the study of immunologic factors in glioma as well as for immunotherapy protocols for treating glioma.

International Journal of Cancer, 2003

An inverse association between self-reported allergies and glioma and meningioma risk, has been p... more An inverse association between self-reported allergies and glioma and meningioma risk, has been previously observed in case-control studies. Approximately 27% (median) of the information on both glioma and meningioma in these studies, however, is collected from proxy respondents. In fact, the odds ratios (OR) among previous brain tumor studies are inversely related to the proportion of proxy respondents (Pearson correlation coefficient = -0.94; 95% CI = -1.00 to -0.65); this correlation suggests bias. We therefore constructed 3 cohorts based on the Swedish Twin, Hospital Discharge, and Cancer Registries. In Cohorts I (14,535 people developed 37 gliomas and 41 meningiomas) and II (29,573 people developed 42 gliomas and 26 meningiomas) median time from self-report of allergies to brain tumor diagnosis was 15.4 years. Cohort III, which overlaps with Cohorts I and II (52,067 people developed 68 gliomas and 63 meningiomas), was linked to the Swedish Hospital Discharge Registry where pre-brain tumor immune-related discharge diagnoses were recorded. Allergies are inversely associated with glioma risk in Cohort I (Hazard ratio [HR] = 0.45; 95% CI = 0.19-1.07) and among high grade (III and IV, HR = 0.45; 95% CI = 0.11-1.92) but not low grade (I and II, HR = 2.60; 95% CI = 0.86-7.81) gliomas in Cohort II. In Cohort III, immune-related discharge diagnoses are also inversely associated with glioma (HR = 0.46; 95% CI = 0.14-1.49). There is no strong evidence against (and some for) the hypothesis that allergies reduce glioma risk.

Gynecologic Oncology, 1989

Epidemiology, 1994

Apparent relative sensitivity, based on an investigator&amp;#39;s external standard, is t... more Apparent relative sensitivity, based on an investigator&amp;#39;s external standard, is the ratio of observed case to control exposure sensitivity. An apparent relative sensitivity different from 1.0 is usually interpreted as evidence for differential misclassification of exposure status. We undertook this investigation to determine the conditions under which an apparent relative sensitivity exceeding 1.0 is actually due to differential misclassification. We also consider whether apparent relative sensitivity correctly quantifies the degree of differential misclassification. To achieve these goals, we derived an algebraic relation involving apparent relative sensitivity, true sensitivities and specificities, true odds ratio, an index of how well the external standard classifies true exposure, and the incidence of the disease among the nonexposed. We found that an apparent relative sensitivity greater than 1.0 correctly indicates differential misclassification when either (1) the investigator&amp;#39;s external standard classifies true exposure perfectly, or (2) the investigator&amp;#39;s external standard is imperfect, but the true odds ratio equals 1.0, true relative sensitivity is greater than 1.0, and true relative specificity is less than 1.0. We also found that apparent relative sensitivity greater than 1.0 falsely suggests differential misclassification when true relative sensitivity equals 1.0, the investigator&amp;#39;s external standard is imperfect, and the true odds ratio is greater than 1.0. Furthermore, even when apparent relative sensitivity correctly detects the presence of differential misclassification, it may misrepresent the degree.

Communication Research, 1990

... Coded language, humor, and metaphor reflect the beliefs and values of a person talking, wheth... more ... Coded language, humor, and metaphor reflect the beliefs and values of a person talking, whether the talk is about apocalypse, politics, economics, or AIDS. Coded Language The referents in language are not always isomorphic with literal meaning. ...

Cancer Research, 2005

A reduced risk of primary malignant adult brain tumors is observed among people reporting asthma,... more A reduced risk of primary malignant adult brain tumors is observed among people reporting asthma, hay fever, and other allergic conditions; however, findings may be attributed to prediagnostic effects of tumors or recall bias. To determine whether asthma and allergic condition polymorphisms are inversely related to glioblastoma multiforme (GBM) risk, we conducted a population-based case-control study of 111 GBM patients and 422 controls. We identified five single nucleotide polymorphisms on three genes previously associated with asthma [interleukin (IL)-4RA, IL-13, ADAM33] and one gene associated with inflammation (cyclooxygenase-2). Confirming previous literature, we found that self-reported asthma, eczema, and fever are inversely related to GBM [e.g., asthma odds ratio (OR), 0.64; 95% confidence interval (CI), 0.33-1.25]. In addition, IL-4RA Ser478Pro TC, CC, and IL-4RA Gln551Arg AG, AA are positively associated with GBM (OR, 1.64; 95% CI, 1.05-2.55; 1.61; 95% CI, 1.05-2.47), whereas IL-13 À1,112 CT, TT is negatively associated with GBM (0.56; 95% CI, 0.33-0.96). Each of these polymorphism-GBM associations is in the opposite direction of a corresponding polymorphismasthma association, consistent with previous findings that selfreported asthmatics and people with allergic conditions are less likely to have GBM than are people who do not report these conditions. Because we used germ line polymorphisms as biomarkers of susceptibility to asthma and allergic conditions, our results cannot be attributed to recall bias or effects of GBM on the immune system. However, our findings are also consistent with associations between IL-4RA, IL-13, and GBM that are independent of their role in allergic conditions.

Cancer Epidemiology Biomarkers & Prevention, 2005

We conducted a case-control study to evaluate the preclinical association between epilepsy, diabe... more We conducted a case-control study to evaluate the preclinical association between epilepsy, diabetes, and stroke and primary adult brain tumors. We first identified all 1,501 low-grade glioma, 4,587 high-grade glioma (HGG), and 4,193 meningioma cases reported to the Swedish Cancer Registry from 1987 to 1999. Next, controls (137,485) were randomly selected from the continuously updated Swedish Population Registry and matched to cases diagnosed that year on age and sex. Finally, cases and controls were linked to the Swedish Hospital Discharge Registry (1969-1999). We found that z z z8 years before HGG diagnosis (or control reference year) there was an elevated risk of HGG among people discharged with epilepsy [odds ratio (OR), 3.01; 95% confidence interval (95% CI), 1.73-5.22]. Two to 3 years before HGG diagnosis, this risk increased (OR, 5.33; 95% CI, 3.58-7.93) and was especially strong among people ages <55 years (OR, 13.49; 95% CI, 6.99-25.94). During this 2-to 3-year prediagnostic period, we also found an increased risk of HGG among people discharged with meningitis (OR, 3.02; 95% CI, 1.06-8.59) or viral encephalitis (OR, 12.64; 95% CI, 2.24-71.24). Results are similar for glioblastoma multiforme, low-grade glioma, and meningioma. In contrast, risk of HGG among people discharged with diabetes or stroke does not increase until year of brain tumor diagnosis. The occurrence of excess epilepsy z z z8 years before HGG diagnosis suggests a relatively long preclinical phase, but excess diabetes or stroke appear late in HGG development.

Archives of Internal Medicine, 2000

Background: Depression predicts morbidity and mortality among individuals who have coronary heart... more Background: Depression predicts morbidity and mortality among individuals who have coronary heart disease (CHD), and there is increasing evidence that depression may also act as an antecedent to CHD. The studies that have reported a relationship between depression and CHD incidence or mortality either were restricted to men only or analyzed women and men together. The present investigation was conducted to evaluate the differential effect depression may have on CHD incidence and mortality in women and men. Research Methods: We analyzed data from 5007 women and 2886 men enrolled in the first National Health and Nutrition Examination Survey (NHANES I) who were free of CHD at the 1982-1984 interview and who had completed the Center for Epidemiologic Studies Depression Scale (CES-D). Participants were evaluated from the 1982 interview date either until the end of the study (1992 interview date) or until the occurrence of a CHD event. Using CHD incidence and CHD mortality (International Classification of Disease, Ninth Revision, codes 410-414) as the outcome variables, Cox proportional hazards regression models were developed to evaluate the relative risk (RR) of CHD incidence and mortality in the depressed women and men separately, controlling for standard CHD risk factors. Results: The women experienced 187 nonfatal and 137 fatal events, compared with 187 nonfatal and 129 fatal events among the men. The adjusted RR of CHD incidence among depressed women was 1.73 (95% confidence internal [CI], 1.11-2.68) compared with nondepressed women. Depression had no effect on CHD mortality in the women (RR, 0.74; 95% CI, 0.40-1.48). The adjusted RR of CHD incidence among depressed men was 1.71 (95% CI, 1.14-2.56) compared with nondepressed men. Depressed men also had an increased risk of CHD mortality compared with their nondepressed counterparts, with an adjusted RR of 2.34 (95% CI, 1.54-3.56). Conclusions: In this sample, while controlling for possible confounding factors, depression was associated with an increased risk of CHD incidence in both men and women, as well as CHD mortality in men. Depression had no effect on CHD mortality in women.

Annals of Epidemiology, 1994

In a 1984 case-control study of cutaneous malignant melanoma (CMM) among workers at the Lawrence ... more In a 1984 case-control study of cutaneous malignant melanoma (CMM) among workers at the Lawrence Livermore National Laboratory, Austin and Reynolds found an association between reported employment in proximity to ionizing radiation and CMM (odds ratio (OR) = 5.4; 95% confidence interval (CI): 1.4, 20.7). But in a preliminary study in 1981, they found no association between individual radiation dosimetry readings and CMM. We reanalyzed the 1984 Austin-Reynolds case-control data to determine whether error or bias explain the inconsistency between reported employment in proximity to radiation and individual radiation dosimetry readings. Using individual radiation dosimetry readings, we developed an index of occupation-specific radiation. This index was associated with case status (OR = 10.8; 95% CI: 1.4, 85.1). No definitive evidence for influential matched sets, confounding, recall bias, or any other sources of bias was identified. These results suggest that the odds ratio for reported employment in proximity to radiation may be valid.

American Journal of Public Health, 1990

To determine whether the sex, race, or sexual preference of a patient infected with immunodeficie... more To determine whether the sex, race, or sexual preference of a patient infected with immunodeficiency virus (HIV) influences a physician's decision to breach patient confidentiality, Tennessee primary care physicians were mailed a questionnaire containing a case study in which an HIV-infected patient presented a risk to a third party. Eight different descriptions of the sex, race, and sexual preference of the hypothetical patient were distributed randomly among the physicians, one description to each physician. The physicians were asked to decide whether to maintain confidentiality, notify the health department, or inform the patient's partner. Responses of 199 White male physicians were analyzed using an unconditional saturated logistic regression model. The odds ratios for

American Journal of Epidemiology, 2007

A small number of prior epidemiologic studies of occupational noise exposure based on self-report... more A small number of prior epidemiologic studies of occupational noise exposure based on self-report have suggested an association with acoustic neuroma. The goal of the present study was to further examine the association between noise exposure and acoustic neuroma by using an objective measure of exposure in the form of a job exposure matrix. A total of 793 acoustic neuroma cases aged 21-84 years were identified between 1987 and 1999 from the Swedish Cancer Registry. The 101,756 controls randomly selected from the study base were frequency matched to cases on age, sex, and calendar year of diagnosis. Occupational information, available for 599 of the cases and 73,432 of the controls, was obtained from censuses and was linked to a job exposure matrix based on actual noise measurements. All risk estimates were close to unity, regardless of noise exposure level or parameter. The overall odds ratio for exposure to 85 dB of noise was 0.89 (95% confidence interval: 0.64, 1.23). Contrary to previous study results, the present findings did not demonstrate an increased acoustic neuroma risk related to occupational noise exposure even after allowing for a long latency period. The effect of nondifferential misclassification of exposure must be considered a potential cause of the negative findings.

Acta Oncologica, 2010

Glioma is the most common type of adult brain tumor and glioblastoma, its most aggressive form, h... more 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 signifi cantly associated with glioma risk at p Ͻ 0.05, and 17 of the SNPs were signifi cantly associated with glioblastoma risk at p Ͻ 0.05. In addition, we found that one EGFR haplotype was related to increased glioblastoma risk at p ϭ 0.009, Odds Ratio [OR] ϭ 1.67 (95% confi dence interval (CI): 1.14, 2.45). The Bonferroni correction made all p-values non-signifi cant. 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] ϭ 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 fi rst to fi nd that certain genotypes of the EGFR gene may be related to glioblastoma risk. Further studies are required to reinvestigate these fi ndings and evaluate the functional signifi cance. * Haplotypes with frequency Ն 0.05 in cases and/or controls (rs17172430, rs17172432, rs17172433, rs4947492, rs12718945, rs4947979). H1 ϭ a-c-a-a-g-a; H2 ϭ g-t-g-a-g-a. * Haplotypes with frequency Ն 0.05 in cases and/or controls (rs1476278, rs9303274, rs903501). H1 ϭ a-c-g; H2 ϭ g-t-a.