Last data update: Jun 17, 2024. (Total: 47034 publications since 2009)
Records 1-22 (of 22 Records) |
Query Trace: Butler MA [original query] |
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Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome.
Machiela MJ , Zhou W , Karlins E , Sampson JN , Freedman ND , Yang Q , Hicks B , Dagnall C , Hautman C , Jacobs KB , Abnet CC , Aldrich MC , Amos C , Amundadottir LT , Arslan AA , Beane-Freeman LE , Berndt SI , Black A , Blot WJ , Bock CH , Bracci PM , Brinton LA , Bueno-de-Mesquita HB , Burdett L , Buring JE , Butler MA , Canzian F , Carreon T , Chaffee KG , Chang IS , Chatterjee N , Chen C , Chen C , Chen K , Chung CC , Cook LS , Crous Bou M , Cullen M , Davis FG , De Vivo I , Ding T , Doherty J , Duell EJ , Epstein CG , Fan JH , Figueroa JD , Fraumeni JF , Friedenreich CM , Fuchs CS , Gallinger S , Gao YT , Gapstur SM , Garcia-Closas M , Gaudet MM , Gaziano JM , Giles GG , Gillanders EM , Giovannucci EL , Goldin L , Goldstein AM , Haiman CA , Hallmans G , Hankinson SE , Harris CC , Henriksson R , Holly EA , Hong YC , Hoover RN , Hsiung CA , Hu N , Hu W , Hunter DJ , Hutchinson A , Jenab M , Johansen C , Khaw KT , Kim HN , Kim YH , Kim YT , Klein AP , Klein R , Koh WP , Kolonel LN , Kooperberg C , Kraft P , Krogh V , Kurtz RC , LaCroix A , Lan Q , Landi MT , Marchand LL , Li D , Liang X , Liao LM , Lin D , Liu J , Lissowska J , Lu L , Magliocco AM , Malats N , Matsuo K , McNeill LH , McWilliams RR , Melin BS , Mirabello L , Moore L , Olson SH , Orlow I , Park JY , Patino-Garcia A , Peplonska B , Peters U , Petersen GM , Pooler L , Prescott J , Prokunina-Olsson L , Purdue MP , Qiao YL , Rajaraman P , Real FX , Riboli E , Risch HA , Rodriguez-Santiago B , Ruder AM , Savage SA , Schumacher F , Schwartz AG , Schwartz KL , Seow A , Wendy Setiawan V , Severi G , Shen H , Sheng X , Shin MH , Shu XO , Silverman DT , Spitz MR , Stevens VL , Stolzenberg-Solomon R , Stram D , Tang ZZ , Taylor PR , Teras LR , Tobias GS , Van Den Berg D , Visvanathan K , Wacholder S , Wang JC , Wang Z , Wentzensen N , Wheeler W , White E , Wiencke JK , Wolpin BM , Wong MP , Wu C , Wu T , Wu X , Wu YL , Wunder JS , Xia L , Yang HP , Yang PC , Yu K , Zanetti KA , Zeleniuch-Jacquotte A , Zheng W , Zhou B , Ziegler RG , Perez-Jurado LA , Caporaso NE , Rothman N , Tucker M , Dean MC , Yeager M , Chanock SJ . Nat Commun 2016 7 11843 ![]() To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events >2 Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases. |
Further Confirmation of Germline Glioma Risk Variant rs78378222 in TP53 and Its Implication in Tumor Tissues via Integrative Analysis of TCGA Data.
Wang Z , Rajaraman P , Melin BS , Chung CC , Zhang W , McKean-Cowdin R , Michaud D , Yeager M , Ahlbom A , Albanes D , Andersson U , Freeman LE , Buring JE , Butler MA , Carreon T , Feychting M , Gapstur SM , Gaziano JM , Giles GG , Hallmans G , Henriksson R , Hoffman-Bolton J , Inskip PD , Kitahara CM , Marchand LL , Linet MS , Li S , Peters U , Purdue MP , Rothman N , Ruder AM , Sesso HD , Severi G , Stampfer M , Stevens VL , Visvanathan K , Wang SS , White E , Zeleniuch-Jacquotte A , Hoover R , Fraumeni JF , Chatterjee N , Hartge P , Chanock SJ . Hum Mutat 2015 36 (7) 684-8 ![]() We confirmed strong association of rs78378222:A>C (per allele odds ratio [OR] = 3.14; P = 6.48 x 10-11 ), a germline rare single-nucleotide polymorphism (SNP) in TP53, via imputation of a genome-wide association study of glioma (1,856 cases and 4,955 controls). We subsequently performed integrative analyses on the Cancer Genome Atlas (TCGA) data for GBM (glioblastoma multiforme) and LUAD (lung adenocarcinoma). Based on SNP data, we imputed genotypes for rs78378222 and selected individuals carrying rare risk allele (C). Using RNA sequencing data, we observed aberrant transcripts with approximately 3 kb longer than normal for those individuals. Using exome sequencing data, we further showed that loss of haplotype carrying common protective allele (A) occurred somatically in GBM but not in LUAD. Our bioinformatic analysis suggests rare risk allele (C) disrupts mRNA termination, and an allelic loss of a genomic region harboring common protective allele (A) occurs during tumor initiation or progression for glioma. |
Characterization of large structural genetic mosaicism in human autosomes.
Machiela MJ , Zhou W , Sampson JN , Dean MC , Jacobs KB , Black A , Brinton LA , Chang IS , Chen C , Chen C , Chen K , Cook LS , Crous Bou M , De Vivo I , Doherty J , Friedenreich CM , Gaudet MM , Haiman CA , Hankinson SE , Hartge P , Henderson BE , Hong YC , Hosgood HD 3rd , Hsiung CA , Hu W , Hunter DJ , Jessop L , Kim HN , Kim YH , Kim YT , Klein R , Kraft P , Lan Q , Lin D , Liu J , Le Marchand L , Liang X , Lissowska J , Lu L , Magliocco AM , Matsuo K , Olson SH , Orlow I , Park JY , Pooler L , Prescott J , Rastogi R , Risch HA , Schumacher F , Seow A , Setiawan VW , Shen H , Sheng X , Shin MH , Shu XO , VanDen Berg D , Wang JC , Wentzensen N , Wong MP , Wu C , Wu T , Wu YL , Xia L , Yang HP , Yang PC , Zheng W , Zhou B , Abnet CC , Albanes D , Aldrich MC , Amos C , Amundadottir LT , Berndt SI , Blot WJ , Bock CH , Bracci PM , Burdett L , Buring JE , Butler MA , Carreon T , Chatterjee N , Chung CC , Cook MB , Cullen M , Davis FG , Ding T , Duell EJ , Epstein CG , Fan JH , Figueroa JD , Fraumeni JF Jr , Freedman ND , Fuchs CS , Gao YT , Gapstur SM , Patino-Garcia A , Garcia-Closas M , Gaziano JM , Giles GG , Gillanders EM , Giovannucci EL , Goldin L , Goldstein AM , Greene MH , Hallmans G , Harris CC , Henriksson R , Holly EA , Hoover RN , Hu N , Hutchinson A , Jenab M , Johansen C , Khaw KT , Koh WP , Kolonel LN , Kooperberg C , Krogh V , Kurtz RC , LaCroix A , Landgren A , Landi MT , Li D , Liao LM , Malats N , McGlynn KA , McNeill LH , McWilliams RR , Melin BS , Mirabello L , Peplonska B , Peters U , Petersen GM , Prokunina-Olsson L , Purdue M , Qiao YL , Rabe KG , Rajaraman P , Real FX , Riboli E , Rodriguez-Santiago B , Rothman N , Ruder AM , Savage SA , Schwartz AG , Schwartz KL , Sesso HD , Severi G , Silverman DT , Spitz MR , Stevens VL , Stolzenberg-Solomon R , Stram D , Tang ZZ , Taylor PR , Teras LR , Tobias GS , Viswanathan K , Wacholder S , Wang Z , Weinstein SJ , Wheeler W , White E , Wiencke JK , Wolpin BM , Wu X , Wunder JS , Yu K , Zanetti KA , Zeleniuch-Jacquotte A , Ziegler RG , de Andrade M , Barnes KC , Beaty TH , Bierut LJ , Desch KC , Doheny KF , Feenstra B , Ginsburg D , Heit JA , Kang JH , Laurie CA , Li JZ , Lowe WL , Marazita ML , Melbye M , Mirel DB , Murray JC , Nelson SC , Pasquale LR , Rice K , Wiggs JL , Wise A , Tucker M , Perez-Jurado LA , Laurie CC , Caporaso NE , Yeager M , Chanock SJ . Am J Hum Genet 2015 96 (3) 487-97 ![]() Analyses of genome-wide association study (GWAS) data have revealed that detectable genetic mosaicism involving large (>2 Mb) structural autosomal alterations occurs in a fraction of individuals. We present results for a set of 24,849 genotyped individuals (total GWAS set II [TGSII]) in whom 341 large autosomal abnormalities were observed in 168 (0.68%) individuals. Merging data from the new TGSII set with data from two prior reports (the Gene-Environment Association Studies and the total GWAS set I) generated a large dataset of 127,179 individuals; we then conducted a meta-analysis to investigate the patterns of detectable autosomal mosaicism (n = 1,315 events in 925 [0.73%] individuals). Restricting to events >2 Mb in size, we observed an increase in event frequency as event size decreased. The combined results underscore that the rate of detectable mosaicism increases with age (p value = 5.5 x 10(-31)) and is higher in men (p value = 0.002) but lower in participants of African ancestry (p value = 0.003). In a subset of 47 individuals from whom serial samples were collected up to 6 years apart, complex changes were noted over time and showed an overall increase in the proportion of mosaic cells as age increased. Our large combined sample allowed for a unique ability to characterize detectable genetic mosaicism involving large structural events and strengthens the emerging evidence of non-random erosion of the genome in the aging population. |
Endogenous antibody responsiveness to epidermal growth factor receptor is associated with immunoglobulin allotypes and overall survival of patients with glioblastoma.
Pandey JP , Kistner-Griffin E , Radwan FF , Kaur N , Namboodiri AM , Black L , Butler MA , Carreon T , Ruder AM . Neuro Oncol 2014 17 (5) 678-84 ![]() BACKGROUND: Immunoglobulin gamma marker (GM) and kappa marker (KM) allotypes, hereditary antigenic determinants of gamma and kappa chains, respectively, have been shown to be associated with immunity to a variety of self and nonself antigens, but their possible contribution to immunity to the tumor-associated antigens epidermal growth factor receptor (EGFR) and EGFR variant (v)III has not been evaluated. The aim of the present investigation was to determine whether the interindividual variation in endogenous antibody responsiveness to EGFR and EGFRvIII is associated with particular GM, KM, and Fcgamma receptor (FcgammaR) genotypes and whether antibody levels were associated with the overall survival of patients with glioblastoma. METHODS: A total of 126 Caucasian participants with glioblastoma were genotyped for several GM, KM, and FcgammaR alleles and characterized for IgG antibodies to EGFR and EGFRvIII antigens. RESULTS: The anti-EGFR antibody levels associated with GM 3/3 homozygotes and GM 3/17 heterozygotes were similar (15.9 vs 16.4 arbitrary units [AU]/microL) and significantly lower than those associated with GM 17/17 homozygotes (19.6 AU/microL; nominal P = .007). Participants homozygous for the GM 21 allele also had significantly higher levels of anti-EGFR antibodies than GM 5/5 homozygotes and GM 5/21 heterozygotes (20.1 vs 16.0 and 16.3 AU/microL; nominal P = .005). Similar associations were found with immune responsiveness to EGFRvIII. Higher anti-EGFR and anti-EGFRvIII antibody levels were associated with enhanced overall survival (16 vs 11 mo, nominal P = .038 and 20 vs 11 mo, nominal P = .004, respectively). CONCLUSIONS: GM allotypes contribute to humoral immunity to EGFR in glioblastoma. |
Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33.
Wang Z , Zhu B , Zhang M , Parikh H , Jia J , Chung CC , Sampson JN , Hoskins JW , Hutchinson A , Burdette L , Ibrahim A , Hautman C , Raj PS , Abnet CC , Adjei AA , Ahlbom A , Albanes D , Allen NE , Ambrosone CB , Aldrich M , Amiano P , Amos C , Andersson U , Andriole G Jr , Andrulis IL , Arici C , Arslan AA , Austin MA , Baris D , Barkauskas DA , Bassig BA , Beane Freeman LE , Berg CD , Berndt SI , Bertazzi PA , Biritwum RB , Black A , Blot W , Boeing H , Boffetta P , Bolton K , Boutron-Ruault MC , Bracci PM , Brennan P , Brinton LA , Brotzman M , Bueno-de-Mesquita HB , Buring JE , Butler MA , Cai Q , Cancel-Tassin G , Canzian F , Cao G , Caporaso NE , Carrato A , Carreon T , Carta A , Chang GC , Chang IS , Chang-Claude J , Che X , Chen CJ , Chen CY , Chen CH , Chen C , Chen KY , Chen YM , Chokkalingam AP , Chu LW , Clavel-Chapelon F , Colditz GA , Colt JS , Conti D , Cook MB , Cortessis VK , Crawford ED , Cussenot O , Davis FG , De Vivo I , Deng X , Ding T , Dinney CP , Di Stefano AL , Diver WR , Duell EJ , Elena JW , Fan JH , Feigelson HS , Feychting M , Figueroa JD , Flanagan AM , Fraumeni JF Jr , Freedman ND , Fridley BL , Fuchs CS , Gago-Dominguez M , Gallinger S , Gao YT , Gapstur SM , Garcia-Closas M , Garcia-Closas R , Gastier-Foster JM , Gaziano JM , Gerhard DS , Giffen CA , Giles GG , Gillanders EM , Giovannucci EL , Goggins M , Gokgoz N , Goldstein AM , Gonzalez C , Gorlick R , Greene MH , Gross M , Grossman HB , Grubb R 3rd , Gu J , Guan P , Haiman CA , Hallmans G , Hankinson SE , Harris CC , Hartge P , Hattinger C , Hayes RB , He Q , Helman L , Henderson BE , Henriksson R , Hoffman-Bolton J , Hohensee C , Holly EA , Hong YC , Hoover RN , Hosgood HD 3rd , Hsiao CF , Hsing AW , Hsiung CA , Hu N , Hu W , Hu Z , Huang MS , Hunter DJ , Inskip PD , Ito H , Jacobs EJ , Jacobs KB , Jenab M , Ji BT , Johansen C , Johansson M , Johnson A , Kaaks R , Kamat AM , Kamineni A , Karagas M , Khanna C , Khaw KT , Kim C , Kim IS , Kim YH , Kim YC , Kim YT , Kang CH , Jung YJ , Kitahara CM , Klein AP , Klein R , Kogevinas M , Koh WP , Kohno T , Kolonel LN , Kooperberg C , Kratz CP , Krogh V , Kunitoh H , Kurtz RC , Kurucu N , Lan Q , Lathrop M , Lau CC , Lecanda F , Lee KM , Lee MP , Le Marchand L , Lerner SP , Li D , Liao LM , Lim WY , Lin D , Lin J , Lindstrom S , Linet MS , Lissowska J , Liu J , Ljungberg B , Lloreta J , Lu D , Ma J , Malats N , Mannisto S , Marina N , Mastrangelo G , Matsuo K , McGlynn KA , McKean-Cowdin R , McNeill LH , McWilliams RR , Melin BS , Meltzer PS , Mensah JE , Miao X , Michaud DS , Mondul AM , Moore LE , Muir K , Niwa S , Olson SH , Orr N , Panico S , Park JY , Patel AV , Patino-Garcia A , Pavanello S , Peeters PH , Peplonska B , Peters U , Petersen GM , Picci P , Pike MC , Porru S , Prescott J , Pu X , Purdue MP , Qiao YL , Rajaraman P , Riboli E , Risch HA , Rodabough RJ , Rothman N , Ruder AM , Ryu JS , Sanson M , Schned A , Schumacher FR , Schwartz AG , Schwartz KL , Schwenn M , Scotlandi K , Seow A , Serra C , Serra M , Sesso HD , Severi G , Shen H , Shen M , Shete S , Shiraishi K , Shu XO , Siddiq A , Sierrasesumaga L , Sierri S , Sihoe AD , Silverman DT , Simon M , Southey MC , Spector L , Spitz M , Stampfer M , Stattin P , Stern MC , Stevens VL , Stolzenberg-Solomon RZ , Stram DO , Strom SS , Su WC , Sund M , Sung SW , Swerdlow A , Tan W , Tanaka H , Tang W , Tang ZZ , Tardon A , Tay E , Taylor PR , Tettey Y , Thomas DM , Tirabosco R , Tjonneland A , Tobias GS , Toro JR , Travis RC , Trichopoulos D , Troisi R , Truelove A , Tsai YH , Tucker MA , Tumino R , Van Den Berg D , Van Den Eeden SK , Vermeulen R , Vineis P , Visvanathan K , Vogel U , Wang C , Wang C , Wang J , Wang SS , Weiderpass E , Weinstein SJ , Wentzensen N , Wheeler W , White E , Wiencke JK , Wolk A , Wolpin BM , Wong MP , Wrensch M , Wu C , Wu T , Wu X , Wu YL , Wunder JS , Xiang YB , Xu J , Yang HP , Yang PC , Yatabe Y , Ye Y , Yeboah ED , Yin Z , Ying C , Yu CJ , Yu K , Yuan JM , Zanetti KA , Zeleniuch-Jacquotte A , Zheng W , Zhou B , Mirabello L , Savage SA , Kraft P , Chanock SJ , Yeager M , Landi MT , Shi J , Chatterjee N , Amundadottir LT . Hum Mol Genet 2014 23 (24) 6616-33 ![]() Genome-wide association studies (GWAS) have mapped risk alleles for at least ten distinct cancers to a small region of 63,000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (ASSET) across six distinct cancers in 34,248 cases and 45,036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single nucleotide polymorphisms (SNPs): five in the TERT gene (region 1: rs7726159, P=2.10x10-39; region 3: rs2853677, P=3.30x10-36 and PConditional=2.36x10-8; region 4: rs2736098, P=3.87x10-12 and PConditional=5.19x10-6, region 5: rs13172201, P=0.041 and PConditional=2.04x10-6; and region 6: rs10069690, P=7.49x10-15 and PConditional=5.35x10-7) and one in the neighboring CLPTM1L gene (region 2: rs451360; P=1.90x10-18 and PConditional=7.06x10-16). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele specific effects on DNA methylation were seen for a subset of risk loci indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci. |
Immunoglobulin genes influence the magnitude of humoral immunity to cytomegalovirus glycoprotein B.
Pandey JP , Kistner-Griffin E , Radwan FF , Kaur N , Namboodiri AM , Black L , Butler MA , Carreon T , Ruder AM . J Infect Dis 2014 210 (11) 1823-6 ![]() Human cytomegalovirus (HCMV) is a risk factor for many human diseases, but among exposed individuals, not everyone is equally likely to develop HCMV-spurred diseases, implying the presence of host genetic factors that might modulate immunity to this virus. Here, we show that antibody responsiveness to HCMV glycoprotein B (gB) is significantly associated with particular immunoglobulin GM (gamma marker) genotypes: Anti-HCMV gB antibody levels were the highest in GM 17/17 homozygotes, intermediate in GM 3/17 heterozygotes, and the lowest in GM 3/3 homozygotes (28.2, 19.0, and 8.1 microg/mL, respectively; p=0.014). These findings provide mechanistic insights in the etiopathogenesis of HCMV-spurred diseases. |
Joint effects between five identified risk variants, allergy, and autoimmune conditions on glioma risk
Safaeian M , Rajaraman P , Hartge P , Yeager M , Linet M , Butler MA , Ruder AM , Purdue MP , Hsing A , Beane-Freeman L , Hoppin JA , Albanes D , Weinstein SJ , Inskip PD , Brenner A , Rothman N , Chatterjee N , Gillanders EM , Chanock SJ , Wang SS . Cancer Causes Control 2013 24 (10) 1885-91 ![]() Common variants in two of the five genetic regions recently identified from genome-wide association studies (GWAS) of risk of glioma were reported to interact with a history of allergic symptoms. In a pooled analysis of five epidemiologic studies, we evaluated the association between the five GWAS implicated gene variants and allergies and autoimmune conditions (AIC) on glioma risk (851 adult glioma cases and 3,977 controls). We further evaluated the joint effects between allergies and AIC and these gene variants on glioma risk. Risk estimates were calculated as odds ratios (OR) and 95 % confidence intervals (95 % CI), adjusted for age, gender, and study. Joint effects were evaluated by conducting stratified analyses whereby the risk associations (OR and 95 % CI) with the allergy or autoimmune conditions for glioma were evaluated by the presence or absence of the 'at-risk' variant, and estimated p interaction by fitting models with the main effects of allergy or autoimmune conditions and genotype and an interaction (product) term between them. Four of the five SNPs previously reported by others were statistically significantly associated with increased risk of glioma in our study (rs2736100, rs4295627, rs4977756, and rs6010620); rs498872 was not associated with glioma in our study. Reporting any allergies or AIC was associated with reduced risks of glioma (allergy: adjusted OR = 0.71, 95 % CI 0.55-0.91; AIC: adjusted OR = 0.65, 95 % CI 0.47-0.90). We did not observe differential association between allergic or autoimmune conditions and glioma by genotype, and there were no statistically significant p interactions. Stratified analysis by glioma grade (low and high grade) did not suggest risk differences by disease grade. Our results do not provide evidence that allergies or AIC modulate the association between the four GWAS-identified SNPs examined and risk of glioma. |
Known glioma risk loci are associated with glioma with a family history of brain tumours -- a case-control gene association study.
Melin B , Dahlin AM , Andersson U , Wang Z , Henriksson R , Hallmans G , Bondy ML , Johansen C , Feychting M , Ahlbom A , Kitahara CM , Wang SS , Ruder AM , Carreon T , Butler MA , Inskip PD , Purdue M , Hsing AW , Mechanic L , Gillanders E , Yeager M , Linet M , Chanock SJ , Hartge P , Rajaraman P . Int J Cancer 2012 132 (10) 2464-8 ![]() Familial cancer can be used to leverage genetic association studies. Recent genome-wide association studies have reported independent associations between seven single nucleotide polymorphisms (SNPs) and risk of glioma. The aim of this study was to investigate whether glioma cases with a positive family history of brain tumours, defined as having at least one first or second degree relative with a history of brain tumour, are associated with known glioma risk loci. 1431 glioma cases and 2868 cancer-free controls were identified from four case-control studies and two prospective cohorts from USA, Sweden, and Denmark and genotyped for seven SNPs previously reported to be associated with glioma risk in case-control designed studies. Odds ratios were calculated by unconditional logistic regression. In analyses including glioma cases with a family history of brain tumours (n=104) and control subjects free of glioma at baseline, three out of seven SNPs were associated with glioma risk; rs2736100 (5p15.33, TERT), rs4977756 (9p21.3, CDKN2A-CDKN2B), and rs6010620 (20q13.33, RTEL1). After Bonferroni correction for multiple comparisons, only one marker was statistically significantly associated with glioma risk, rs6010620 (OR(trend) for the minor (A) allele, 0.39; 95% CI, 0.25-0.61; Bonferroni adjusted p(trend), 1.7x10(-4) ). In conclusion, as previously shown for glioma regardless of family history of brain tumours, rs6010620 (RTEL1) was associated with an increased risk of glioma when restricting to cases with family history of brain tumours. These findings require confirmation in further studies with a larger number of glioma cases with a family history of brain tumours. |
Genome-wide association study of glioma and meta-analysis.
Rajaraman P , Melin BS , Wang Z , McKean-Cowdin R , Michaud DS , Wang SS , Bondy M , Houlston R , Jenkins RB , Wrensch M , Yeager M , Ahlbom A , Albanes D , Andersson U , Freeman LE , Buring JE , Butler MA , Braganza M , Carreon T , Feychting M , Fleming SJ , Gapstur SM , Gaziano JM , Giles GG , Hallmans G , Henriksson R , Hoffman-Bolton J , Inskip PD , Johansen C , Kitahara CM , Lathrop M , Liu C , Le Marchand L , Linet MS , Lonn S , Peters U , Purdue MP , Rothman N , Ruder AM , Sanson M , Sesso HD , Severi G , Shu XO , Simon M , Stampfer M , Stevens VL , Visvanathan K , White E , Wolk A , Zeleniuch-Jacquotte A , Zheng W , Decker P , Enciso-Mora V , Fridley B , Gao YT , Kosel M , Lachance DH , Lau C , Rice T , Swerdlow A , Wiemels JL , Wiencke JK , Shete S , Xiang YB , Xiao Y , Hoover RN , Fraumeni JF Jr , Chatterjee N , Hartge P , Chanock SJ . Hum Genet 2012 131 (12) 1877-88 ![]() Gliomas account for approximately 80 % of all primary malignant brain tumors and, despite improvements in clinical care over the last 20 years, remain among the most lethal tumors, underscoring the need for gaining new insights that could translate into clinical advances. Recent genome-wide association studies (GWAS) have identified seven new susceptibility regions. We conducted a new independent GWAS of glioma using 1,856 cases and 4,955 controls (from 14 cohort studies, 3 case-control studies, and 1 population-based case-only study) and found evidence of strong replication for three of the seven previously reported associations at 20q13.33 (RTEL), 5p15.33 (TERT), and 9p21.3 (CDKN2BAS), and consistent association signals for the remaining four at 7p11.2 (EGFR both loci), 8q24.21 (CCDC26) and 11q23.3 (PHLDB1). The direction and magnitude of the signal were consistent for samples from cohort and case-control studies, but the strength of the association was more pronounced for loci rs6010620 (20q,13.33; RTEL) and rs2736100 (5p15.33, TERT) in cohort studies despite the smaller number of cases in this group, likely due to relatively more higher grade tumors being captured in the cohort studies. We further examined the 85 most promising single nucleotide polymorphism (SNP) markers identified in our study in three replication sets (5,015 cases and 11,601 controls), but no new markers reached genome-wide significance. Our findings suggest that larger studies focusing on novel approaches as well as specific tumor subtypes or subgroups will be required to identify additional common susceptibility loci for glioma risk. |
The Upper Midwest Health Study: gliomas and occupational exposure to chlorinated solvents
Ruder AM , Yiin JH , Waters MA , Carreon T , Hein MJ , Butler MA , Calvert GM , Davis-King KE , Schulte PA , Mandel JS , Morton RF , Reding DJ , Rosenman KD , Stewart PA . Occup Environ Med 2012 70 (2) 73-80 ![]() OBJECTIVES: Occupational exposure to chlorinated aliphatic solvents has been associated with an increased cancer risk, including brain cancer. However, many of these solvents remain in active, large-volume use. We evaluated glioma risk from non-farm occupational exposure (ever/never and estimated cumulative exposure) to any of the six chlorinated solvents-carbon tetrachloride, chloroform, methylene chloride, trichloroethylene, tetrachloroethylene or 1,1,1-trichloroethane-among 798 cases and 1175 population-based controls, aged 18-80 years and non-metropolitan residents of Iowa, Michigan, Minnesota and Wisconsin. METHODS: Solvent use was estimated based on occupation, industry and era, using a bibliographic database of published exposure levels and exposure determinants. Unconditional logistic regression was used to calculate ORs adjusted for frequency matching variables age group and sex, and age and education. Additional analyses were limited to 904 participants who donated blood specimens (excluding controls reporting a previous diagnosis of cancer) genotyped for glutathione-S-transferases GSTP1, GSTM3 and GSTT1. Individuals with functional GST genes might convert chlorinated solvents crossing the blood-brain barrier into cytotoxic metabolites. RESULTS: Both estimated cumulative exposure (ppm-years) and ever exposure to chlorinated solvents were associated with decreased glioma risk and were statistically significant overall and for women. In analyses comparing participants with a high probability of exposure with the unexposed, no associations were statistically significant. Solvent-exposed participants with functional GST genes were not at increased risk of glioma. CONCLUSIONS: We observed no associations of glioma risk and chlorinated solvent exposure. Large pooled studies are needed to explore the interaction of genetic pathways and environmental and occupational exposures in glioma aetiology. |
The Upper Midwest Health Study: industry and occupation of glioma cases and controls
Ruder AM , Waters MA , Carreon T , Butler MA , Calvert GM , Davis-King KE , Waters KM , Schulte PA , Mandel JS , Morton RF , Reding DJ , Rosenman KD . Am J Ind Med 2012 55 (9) 747-55 BACKGROUND: Understanding glioma etiology requires determining which environmental factors are associated with glioma. Upper Midwest Health Study case-control participant work histories collected 1995-1998 were evaluated for occupational associations with glioma. "Exposures of interest" from our study protocol comprise our a priori hypotheses. MATERIALS AND METHODS: Year-long or longer jobs for 1,973 participants were assigned Standard Occupational Classifications (SOC) and Standard Industrial Classifications (SIC). The analysis file includes 8,078 SIC- and SOC-coded jobs. For each individual, SAS 9.2 programs collated employment with identical SIC-SOC coding. Distributions of longest "total employment duration" (total years worked in jobs with identical industry and occupation codes, including multiple jobs, and non-consecutive jobs) were compared between cases and controls, using an industrial hygiene algorithm to group occupations. RESULTS: Longest employment duration was calculated for 780 cases and 1,156 controls. More case than control longest total employment duration was in the "engineer, architect" occupational group [16 cases, 10 controls, odds ratio (OR) 2.50, adjusted for age group, sex, age and education, 95% confidence interval (CI) 1.12-5.60]. Employment as a food processing worker [mostly butchers and meat cutters] was of borderline significance (27 cases, 21 controls, adjusted OR: 1.78, CI: 0.99-3.18). CONCLUSIONS: Among our exposures of interest work as engineers or as butchers and meat cutters was associated with increased glioma risk. Significant associations could be due to chance, because of multiple comparisons, but similar findings have been reported for other glioma studies. Our results suggest some possible associations but by themselves could not provide conclusive evidence. (Am. J. Ind. Med. (c) 2012 Wiley Periodicals, Inc.) |
Evaluation and comparison of urinary metabolic biomarkers of exposure for the jet fuel JP-8
B'Hymer C , Krieg E Jr , Cheever KL , Toennis CA , Clark JC , Kesner JS , Gibson R , Butler MA . J Toxicol Environ Health A 2012 75 (11) 661-72 A study of workers exposed to jet fuel propellant 8 (JP-8) was conducted at U.S. Air Force bases and included the evaluation of three biomarkers of exposure: S-benzylmercapturic acid (BMA), S-phenylmercapturic acid (PMA), and (2-methoxyethoxy)acetic acid (MEAA). Postshift urine specimens were collected from various personnel categorized as high (n = 98), moderate (n = 38) and low (n = 61) JP-8 exposure based on work activities. BMA and PMA urinary levels were determined by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), and MEAA urinary levels were determined by gas chromatography-mass spectrometry (GC-MS). The numbers of samples determined as positive for the presence of the BMA biomarker (above the test method's limit of detection [LOD = 0.5 ng/ml]) were 96 (98.0%), 37 (97.4%), and 58 (95.1%) for the high, moderate, and low (control) exposure workgroup categories, respectively. The numbers of samples determined as positive for the presence of the PMA biomarker (LOD = 0.5 ng/ml) were 33 (33.7%), 9 (23.7%), and 12 (19.7%) for the high, moderate, and low exposure categories. The numbers of samples determined as positive for the presence of the MEAA biomarker (LOD = 0.1 mcg/ml) were 92 (93.4%), 13 (34.2%), and 2 (3.3%) for the high, moderate, and low exposure categories. Statistical analysis of the mean levels of the analytes demonstrated MEAA to be the most accurate or appropriate biomarker for JP-8 exposure using urinary concentrations either adjusted or not adjusted for creatinine; mean levels of BMA and PMA were not statistically significant between workgroup categories after adjusting for creatinine. |
The Upper Midwest Health Study: a case-control study of pesticide applicators and risk of glioma
Yiin JH , Ruder AM , Stewart PA , Waters MA , Carreon T , Butler MA , Calvert GM , Davis-King KE , Schulte PA , Mandel JS , Morton RF , Reding DJ , Rosenman KD . Environ Health 2012 11 (1) 39 BACKGROUND: An excess incidence of brain cancer in farmers has been noted in several studies. The National Institute for Occupational Safety and Health developed the Upper Midwest Health Study (UMHS) as a case-control study of intracranial gliomas and pesticide uses among rural residents. Previous studies of UMHS participants, using "ever-never" exposure to farm pesticides and analyzing men and women separately, found no positive association of farm pesticide exposure and glioma risks. The primary objective was to determine if quantitatively estimated exposure of pesticide applicators was associated with an increased risk of glioma in male and female participants. METHODS: The study included 798 histologically confirmed primary intracranial glioma cases (45 % with proxy respondents) and 1,175 population-based controls, all adult (age 18-80) nonmetropolitan residents of Iowa, Michigan, Minnesota, and Wisconsin. The analyses used quantitatively estimated exposure from questionnaire responses evaluated by an experienced industrial hygienist with 25 years of work on farm pesticide analyses. Odds ratios (ORs) and 95 % confidence intervals (CIs) using unconditional logistic regression modeling were calculated adjusting for frequency-matching variables (10-year age group and sex), and for age and education (a surrogate for socioeconomic status). Analyses were separately conducted with or without proxy respondents. RESULTS: No significant positive associations with glioma were observed with cumulative years or estimated lifetime cumulative exposure of farm pesticide use. There was, a significant inverse association for phenoxy pesticide used on the farm (OR 0.96 per 10 g-years of cumulative exposure, CI 0.93-0.99). No significant findings were observed when proxy respondents were excluded. Non-farm occupational applicators of any pesticide had decreased glioma risk: OR 0.72, CI 0.52-0.99. Similarly, house and garden pesticide applicators had a decreased risk of glioma: OR 0.79, CI 0.66-0.93, with statistically significant inverse associations for use of 2,4-D, arsenates, organophosphates, and phenoxys. CONCLUSIONS: These results are consistent with our previous findings for UMHS of reported farm pesticide exposure and support a lack of positive association between pesticides and glioma. |
Detection of DNA damage in workers exposed to JP-8 jet fuel
Krieg Jr EF , Mathias PI , Toennis CA , Clark JC , Marlow KL , B'Hymer C , Singh NP , Gibson RL , Butler MA . Mutat Res 2012 747 (2) 218-27 The genotoxicity of jet propulsion fuel 8 (JP-8) was assessed in the leukocytes of archived blood specimens from U.S. Air Force personnel using the comet assay. No differences in mean comet assay measurements were found between low, moderate, and high exposure groups before or after a 4hour work shift. Before the work shift, mean tail DNA and mean tail (Olive) moment increased as the concentration of benzene measured in end-exhaled breath increased, indicating that prior environmental or work-related exposures to benzene produced DNA damage. The number of cells with highly damaged DNA decreased as the pre-shift benzene concentration in breath increased. It is not clear why the decrease is occurring. Mean tail DNA and mean tail (Olive) moment decreased as the concentrations of benzene and naphthalene measured in breath immediately after the work shift increased. These inverse relationships may reflect a slower rate of absorption or a faster rate of expiration of benzene in the lung. The number of cells with highly damaged DNA increased as the concentration of urinary (2-methoxyethoxy)acetic acid (MEAA) increased. This relationship was not seen in urinary MEAA adjusted for creatinine. MEAA is a metabolite of the deicing agent 2-(2-methoxyethoxy)ethanol contained in JP-8. MEAA or a component of JP-8 correlated with MEAA may have a toxic effect on DNA. |
Detectable clonal mosaicism and its relationship to aging and cancer.
Jacobs KB , Yeager M , Zhou W , Wacholder S , Wang Z , Rodriguez-Santiago B , Hutchinson A , Deng X , Liu C , Horner MJ , Cullen M , Epstein CG , Burdett L , Dean MC , Chatterjee N , Sampson J , Chung CC , Kovaks J , Gapstur SM , Stevens VL , Teras LT , Gaudet MM , Albanes D , Weinstein SJ , Virtamo J , Taylor PR , Freedman ND , Abnet CC , Goldstein AM , Hu N , Yu K , Yuan JM , Liao L , Ding T , Qiao YL , Gao YT , Koh WP , Xiang YB , Tang ZZ , Fan JH , Aldrich MC , Amos C , Blot WJ , Bock CH , Gillanders EM , Harris CC , Haiman CA , Henderson BE , Kolonel LN , Le Marchand L , McNeill LH , Rybicki BA , Schwartz AG , Signorello LB , Spitz MR , Wiencke JK , Wrensch M , Wu X , Zanetti KA , Ziegler RG , Figueroa JD , Garcia-Closas M , Malats N , Marenne G , Prokunina-Olsson L , Baris D , Schwenn M , Johnson A , Landi MT , Goldin L , Consonni D , Bertazzi PA , Rotunno M , Rajaraman P , Andersson U , Freeman LE , Berg CD , Buring JE , Butler MA , Carreon T , Feychting M , Ahlbom A , Gaziano JM , Giles GG , Hallmans G , Hankinson SE , Hartge P , Henriksson R , Inskip PD , Johansen C , Landgren A , McKean-Cowdin R , Michaud DS , Melin BS , Peters U , Ruder AM , Sesso HD , Severi G , Shu XO , Visvanathan K , White E , Wolk A , Zeleniuch-Jacquotte A , Zheng W , Silverman DT , Kogevinas M , Gonzalez JR , Villa O , Li D , Duell EJ , Risch HA , Olson SH , Kooperberg C , Wolpin BM , Jiao L , Hassan M , Wheeler W , Arslan AA , Bueno-de-Mesquita HB , Fuchs CS , Gallinger S , Gross MD , Holly EA , Klein AP , LaCroix A , Mandelson MT , Petersen G , Boutron-Ruault MC , Bracci PM , Canzian F , Chang K , Cotterchio M , Giovannucci EL , Goggins M , Hoffman Bolton JA , Jenab M , Khaw KT , Krogh V , Kurtz RC , McWilliams RR , Mendelsohn JB , Rabe KG , Riboli E , Tjønneland A , Tobias GS , Trichopoulos D , Elena JW , Yu H , Amundadottir L , Stolzenberg-Solomon RZ , Kraft P , Schumacher F , Stram D , Savage SA , Mirabello L , Andrulis IL , Wunder JS , Patiño García A , Sierrasesúmaga L , Barkauskas DA , Gorlick RG , Purdue M , Chow WH , Moore LE , Schwartz KL , Davis FG , Hsing AW , Berndt SI , Black A , Wentzensen N , Brinton LA , Lissowska J , Peplonska B , McGlynn KA , Cook MB , Graubard BI , Kratz CP , Greene MH , Erickson RL , Hunter DJ , Thomas G , Hoover RN , Real FX , Fraumeni JF Jr , Caporaso NE , Tucker M , Rothman N , Pérez-Jurado LA , Chanock SJ . Nat Genet 2012 44 (6) 651-8 ![]() In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 x 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 x 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases. |
Semi-quantitative analysis of influenza samples using the Luminex xTAG(®) respiratory viral panel kit.
Smith J , Sammons D , Toennis C , Butler MA , Blachere F , Beezhold D . Toxicol Mech Methods 2011 22 (3) 211-7 ![]() The Luminex xTAG(R) respiratory viral panel (RVP) kit simultaneously detects and identifies multiple respiratory viruses including several subtypes of influenza A using a multiplex nucleic acid amplification test assay platform. The emitted fluorescence signal from the RVP assay provides qualitative information on the presence of a particular viral species in respiratory specimens. However, a quantitative assessment is preferred when monitoring environmental samples for respiratory viruses. In this study, we explored the potential use of the RVP kit as a semi-quantitative screening assay for influenza virus detection. The concentration- response of the RVP assay was modeled using four-parameter logistic (4-PL) fits of mean fluorescence intensity (MFI) versus dilute ranges of the influenza A matrix gene, seasonal influenza vaccine, and 2009 H1N1 influenza vaccine. The goodness of fit of the 4-PL model was evaluated by comparing the copy number determined with the fitted model (observed copy number) with the copy number calculated from the dilution of the matrix DNA or vaccine (expected copy number). For the matrix DNA and 2009 H1N1 vaccine, the 4-PL model provided good fit for the influenza A RVP assay response over factors of 10(3) to 10(4). For seasonal influenza vaccine, the model provided good fit for RVP assay response to influenza A, influenza B, H1, and H3. |
The utility of naphthyl-keratin adducts as biomarkers for jet-fuel exposure
Kang-Sickel JC , Butler MA , Frame L , Serdar B , Chao YC , Egeghy P , Rappaport SM , Toennis CA , Li W , Borisova T , French JE , Nylander-French LA . Biomarkers 2011 16 (7) 590-9 We investigated the association between biomarkers of dermal exposure, naphthyl-keratin adducts (NKA), and urine naphthalene biomarker levels in 105 workers routinely exposed to jet-fuel. A moderate correlation was observed between NKA and urine naphthalene levels (p = 0.061). The NKA, post-exposure breath naphthalene, and male gender were associated with an increase, while CYP2E1*6 DD and GSTT1-plus (++/+-) genotypes were associated with a decrease in urine naphthalene level (p < 0.0001). The NKA show great promise as biomarkers for dermal exposure to naphthalene. Further studies are warranted to characterize the relationship between NKA, other exposure biomarkers, and/or biomarkers of biological effects due to naphthalene and/or PAH exposure. |
(2-Methoxyethoxy)acetic acid: a urinary biomarker of exposure for jet fuel JP-8
B'Hymer C , Mathias P , Krieg E Jr , Cheever KL , Toennis CA , Clark JC , Kesner JS , Gibson RL , Butler MA . Int Arch Occup Environ Health 2011 85 (4) 413-20 PURPOSE: To demonstrate the utility of the urinary metabolite (2-methoxyethoxy)acetic acid (MEAA) as a biomarker of exposure. 2-(2-methoxyethoxy)ethanol [diethylene glycol monomethyl ether] is an anti-icing agent used in the formulation of JP-8, and it is added at a known uniform 0.1% (v/v) concentration to each batch lot. JP-8 is a kerosene-based fuel containing different compounds that vary in the content of every batch/lot of fuel; thus, MEAA has the potential to be a more specific and a consistent quantitative biomarker for JP-8 exposure. METHODS: MEAA was used to measure exposure of jet propulsion fuel 8 (JP-8) in United States Air Force (USAF) personnel working at six airbases within the United States. Post-shift urine specimens from various personnel including high (n = 98), moderate (n = 38), and low (n = 61) exposure workgroup categories were collected and analyzed by a gas chromatographic-mass spectrometric test method. The three exposure groups were evaluated for the number per group positive for MEAA, and a statistical analysis consisted of pair-wise t-tests for unequal variances was used to test for the differences in mean MEAA concentrations between the exposure groups. RESULTS: The number of samples detected as positive for MEAA exposure, that is, those above the test method's limit of detection (LOD = 0.1 mcg/ml), were 92 (93.9%), 13 (34.2%), and 2 (3.3%) for the high, moderate, and low exposure workgroup categories, respectively. The mean urinary MEAA level was significantly greater in the high exposure category (6.8 mcg/ml), compared to the moderate (0.42 mcg/ml) and the low (0.07 mcg/ml) exposure categories. The maximum concentration of urinary MEAA was 110 mcg/ml for the high exposure category, while 4.8 mcg/ml and 0.2 mcg/ml maximum levels were found in the moderate and low exposure categories, respectively. CONCLUSION: This study demonstrated that urinary MEAA can be used as an accurate biomarker of exposure for JP-8 workers and clearly distinguished the differences in JP-8 exposure by workgroup category. |
Cytogenetic analysis of an exposed-referent study: perchloroethylene-exposed dry cleaners compared to unexposed laundry workers
Tucker JD , Sorensen KJ , Ruder AM , McKernan LT , Forrester CL , Butler MA . Environ Health 2011 10 16 ![]() BACKGROUND: Significant numbers of people are exposed to tetrachloroethylene (perchloroethylene, PCE) every year, including workers in the dry cleaning industry. Adverse health effects have been associated with PCE exposure. However, investigations of possible cumulative cytogenetic damage resulting from PCE exposure are lacking. METHODS: Eighteen dry cleaning workers and 18 laundry workers (unexposed controls) provided a peripheral blood sample for cytogenetic analysis by whole chromosome painting. Pre-shift exhaled air on these same participants was collected and analyzed for PCE levels. The laundry workers were matched to the dry cleaners on race, age, and smoking status. The relationships between levels of cytological damage and exposures (including PCE levels in the shop and in workers' blood, packyears, cumulative alcohol consumption, and age) were compared with correlation coefficients and t-tests. Multiple linear regressions considered blood PCE, packyears, alcohol, and age. RESULTS: There were no significant differences between the PCE-exposed dry cleaners and the laundry workers for chromosome translocation frequencies, but PCE levels were significantly correlated with percentage of cells with acentric fragments (R2 = 0.488, p < 0.026). CONCLUSIONS: There does not appear to be a strong effect in these dry cleaning workers of PCE exposure on persistent chromosome damage as measured by translocations. However, the correlation between frequencies of acentric fragments and PCE exposure level suggests that recent exposures to PCE may induce transient genetic damage. More heavily exposed participants and a larger sample size will be needed to determine whether PCE exposure induces significant levels of persistent chromosome damage. |
Risk factors for oligodendroglial tumors: a pooled international study
McCarthy BJ , Rankin KM , Aldape K , Bondy ML , Brannstrom T , Broholm H , Feychting M , Il'yasova D , Inskip PD , Johansen C , Melin BS , Ruder AM , Butler MA , Scheurer ME , Schuz J , Schwartzbaum JA , Wrensch MR , Davis FG . Neuro Oncol 2010 13 (2) 242-50 Oligodendroglial tumors are rare subtypes of brain tumors and are often combined with other glial tumors in epidemiological analyses. However, different demographic associations and clinical characteristics suggest potentially different risk factors. The purpose of this study was to investigate possible risk factors for oligodendroglial tumors (including oligodendroglioma, anaplastic oligodendroglioma, and mixed glioma). Data from 7 case-control studies (5 US and 2 Scandinavian) were pooled. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for age group, gender, and study site. Data on 617 cases and 1260 controls were available for analyses. Using data from all 7 studies, history of allergies and/or asthma was associated with a decreased risk of anaplastic oligodendroglioma (OR = 0.6; 95% CI: 0.4-0.9), and history of asthma only was associated with a decreased risk of oligodendroglioma (OR = 0.5; 95% CI: 0.3-0.9) and anaplastic oligodendroglioma (OR = 0.3; 95% CI: 0.1-0.9). A family history of brain tumors was associated with an increased risk of anaplastic oligodendroglioma (OR = 2.2; 95% CI: 1.1-4.5). Having had chicken pox was associated with a decreased risk of oligodendroglioma (OR = 0.6; 95% CI: 0.4-0.9) and anaplastic oligodendroglioma (OR = 0.5; 95% CI: 0.3-0.9) in the US studies. Although there is some overlap in risk factors between oligodendroglial tumors and gliomas as a group, it is likely that additional factors specific to oligodendroglial tumors have yet to be identified. Large, multi-institution international studies will be necessary to better characterize these etiological risk factors. |
Lead and cognitive function in VDR genotypes in the third National Health and Nutrition Examination Survey.
Krieg EF Jr , Butler MA , Chang MH , Liu T , Yesupriya A , Lindegren ML , Dowling N , CDC NCI NHANES III Genomics Working Group . Neurotoxicol Teratol 2009 32 (2) 262-72 ![]() The relationship between the blood lead concentration and cognitive function in children and adults with different VDR genotypes who participated in the third National Health and Nutrition Examination Survey was investigated. The relationship between blood lead and serum homocysteine concentrations was also investigated. In children 12 to 16years old, performance on the digit span and arithmetic tests as a function of the blood lead concentration varied by VDR rs2239185 and VDR rs731236 genotypes. Decreases in performance occurred in some genotypes, but not in others. In adults 20 to 59years old, performance on the symbol-digit substitution test as a function of the blood lead concentration varied by VDR rs2239185-rs731236 haplotype. In the 12 to 16year old children and adults 60 or more years old, the relationship between the serum homocysteine and blood lead concentrations varied by VDR genotype. The mean blood lead concentrations of the children and adults did not vary by VDR genotype. |
Lead and cognitive function in ALAD genotypes in the third National Health and Nutrition Examination Survey.
Krieg EF Jr , Butler MA , Chang MH , Liu T , Yesupriya A , Lindegren ML , Dowling N , CDC NCI NHANES III Genomics Working Group . Neurotoxicol Teratol 2009 31 (6) 364-71 ![]() The relationship between the blood lead concentration and cognitive function in children and adults with different ALAD genotypes who participated in the third National Health and Nutrition Examination Survey was investigated. The relationship between blood lead and serum homocysteine concentrations was also investigated. In children 12 to 16 years old, no difference in the relationship between cognitive function and blood lead concentration between genotypes was found. In adults 20 to 59 years old, mean reaction time decreased as the blood lead concentration increased in the ALAD rs1800435 CC/CG group. This represents an improvement in performance. In adults 60 years and older, no difference in the relationship between cognitive function and blood lead concentration between genotypes was found. The serum homocysteine concentration increased as the blood lead concentration increased in adults 20 to 59 years old and 60 years and older, but there were no differences between genotypes. The mean blood lead concentration of children with the ALAD rs1800435 CC/CG genotype was less than that of children with the GG genotype. |
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