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1.
Cancer ; 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31415710

RESUMO

BACKGROUND: Discrimination and trust are known barriers to accessing health care. Despite well-documented racial disparities in the ovarian cancer care continuum, the role of these barriers has not been examined. This study evaluated the association of everyday discrimination and trust in physicians with a prolonged interval between symptom onset and ovarian cancer diagnosis (hereafter referred to as prolonged symptom duration). METHODS: Subjects included cases enrolled in the African American Cancer Epidemiology Study, a multisite case-control study of epithelial ovarian cancer among black women. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for associations of everyday discrimination and trust in physicians with a prolonged symptom duration (1 or more symptoms lasting longer than the median symptom-specific duration), and it controlled for access-to-care covariates and potential confounders. RESULTS: Among the 486 cases in this analysis, 302 women had prolonged symptom duration. In the fully adjusted model, a 1-unit increase in the frequency of everyday discrimination increased the odds of prolonged symptom duration 74% (OR, 1.74; 95% CI, 1.22-2.49), but trust in physicians was not associated with prolonged symptom duration (OR, 0.86; 95% CI, 0.66-1.11). CONCLUSIONS: Perceived everyday discrimination was associated with prolonged symptom duration, whereas more commonly evaluated determinants of access to care and trust in physicians were not. These results suggest that more research on the effects of interpersonal barriers affecting ovarian cancer care is warranted.

2.
Neuro Oncol ; 2019 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-31301133

RESUMO

Primary brain tumors account for ~1% of new cancer cases and ~2% of cancer deaths in the United States; however, they are the most commonly occurring solid tumor in children. These tumors are very heterogeneous, and can be broadly classified into malignant and benign (or non-malignant), and these histologies vary in frequency by age, sex, and race/ethnicity. Epidemiological studies have explored numerous potential risk factors, and thus far, the only validated associations for brain tumors are ionizing radiation (which increases risk in both adults and children) and history of allergies (which decreases risk in adults). Studies of genetic risk factors have identified 32 germline variants associated with increased risk for these tumors in adults (25 in glioma, 2 in meningioma, 3 in pituitary adenoma, and 2 in primary CNS lymphoma), and further studies are currently underway for other histological subtypes, as well as for various childhood brain tumors. While identifying risk factors for these tumors is difficult due to their rarity, many existing datasets can be leveraged for future discoveries in multi-institutional collaborations. Many institutions are continuing to develop large clinical databases including pre-diagnostic risk factor data, and developments in molecular characterization of tumor subtypes continue to allow for investigation of more refined phenotypes.

3.
J Nutr ; 149(9): 1606-1616, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31152675

RESUMO

BACKGROUND: Chronic inflammation is associated with ovarian carcinogenesis; yet, the impact of inflammatory-related exposures on outcomes has been understudied. OBJECTIVE: Given the poor survival of women diagnosed with ovarian cancer, especially African-Americans, we examined whether diet-associated inflammation, a modifiable source of chronic systemic inflammation measured by the dietary inflammatory index (DII), was associated with all-cause mortality among African-American women with ovarian carcinoma. METHODS: Data were available from 490 ovarian carcinoma patients enrolled in a population-based case-control study of African-American women with ovarian cancer, the African-American Cancer Epidemiology Study. Energy-adjusted DII (E-DII) scores were calculated based on prediagnostic dietary intake of foods alone or foods and supplements, which was self-reported using the 2005 Block Food Frequency Questionnaire. Cox proportional hazards regression was used to estimate risk of mortality overall and for the most common histotype, high-grade serous carcinoma. Additionally, we assessed interaction by age at diagnosis and smoking status. RESULTS: Women included in this study had a median age of 57 y, and the majority of women were obese (58%), had late-stage disease (Stage III or IV, 66%), and had high-grade serous carcinoma (64%). Greater E-DII scores including supplements (indicating greater inflammatory potential) were associated with an increased risk of mortality among women with high-grade serous carcinoma (HR1-unit change: 1.08; 95% CI: 1.01, 1.17). Similar associations were observed for the E-DII excluding supplements, although not statistically significant (HR1-unit change: 1.07; 95% CI: 0.97, 1.17). There was an interaction by smoking status, where the positive association with mortality was present only among ever smokers (HRQuartile 4/Quartile 1: 2.36; 95% CI: 1.21, 4.60) but not among never smokers. CONCLUSIONS: Greater inflammatory potential of prediagnostic diet may adversely impact prognosis among African-American women with high-grade serous carcinoma, and specifically among ever smokers.

5.
Int J Cancer ; 2019 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-30963577

RESUMO

Glioma incidence is highest in non-Hispanic Whites, and to date, glioma genome-wide association studies (GWAS) to date have only included European ancestry (EA) populations. African Americans and Hispanics in the US have varying proportions of EA, African (AA) and Native American ancestries (NAA). It is unknown if identified GWAS loci or increased EA is associated with increased glioma risk. We assessed whether EA was associated with glioma in African Americans and Hispanics. Data were obtained for 832 cases and 675 controls from the Glioma International Case-Control Study and GliomaSE Case-Control Study previously estimated to have <80% EA, or self-identify as non-White. We estimated global and local ancestry using fastStructure and RFMix, respectively, using 1,000 genomes project reference populations. Within groups with ≥40% AA (AFR≥0.4 ), and ≥15% NAA (AMR≥0.15 ), genome-wide association between local EA and glioma was evaluated using logistic regression conditioned on global EA for all gliomas. We identified two regions (7q21.11, p = 6.36 × 10-4 ; 11p11.12, p = 7.0 × 10-4 ) associated with increased EA, and one associated with decreased EA (20p12.13, p = 0.0026) in AFR≥0.4 . In addition, we identified a peak at rs1620291 (p = 4.36 × 10-6 ) in 7q21.3. Among AMR≥0.15 , we found an association between increased EA in one region (12q24.21, p = 8.38 × 10-4 ), and decreased EA in two regions (8q24.21, p = 0. 0010; 20q13.33, p = 6.36 × 10-4 ). No other significant associations were identified. This analysis identified an association between glioma and two regions previously identified in EA populations (8q24.21, 20q13.33) and four novel regions (7q21.11, 11p11.12, 12q24.21 and 20p12.13). The identifications of novel association with EA suggest regions to target for future genetic association studies.

6.
J Neurooncol ; 142(3): 479-487, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30796745

RESUMO

PURPOSE: Telomere length-associated SNPs have been associated with incidence and survival rates for malignant brain tumors such as glioma. Here, we study the influence of genetically determined lymphocyte telomere length (LTL) by comparing telomerase associated SNPs between the most common non-malignant brain tumor, i.e. meningioma, and healthy controls. METHODS/PATIENTS: One thousand fifty-three (1053) surgically treated meningioma patients and 4437 controls of Western European ancestry were included. Germline DNA was genotyped for 8 SNPs previously significantly associated with LTL. Genotypically-estimated LTL was then calculated by summing each SNP's genotypically-specified telomere length increase in base pairs (bp) for each person. Odds ratios for genotypically-estimated LTL in meningioma cases and controls were evaluated using logistic regression with the first two ancestral principal components and sex as covariates. RESULTS: Three out of the eight evaluated LTL SNPs were significantly associated with increased meningioma risk (rs10936599: OR 1.14, 95% CI 1.01-1.28, rs2736100: OR 1.13, 95% CI 1.03-1.25, rs9420907: OR 1.22, 95% CI 1.07-1.39). Only rs9420907 remained significant after correction for multiple testing. Average genotypically-estimated LTL was significantly longer for those with meningioma compared to controls [mean cases: 560.2 bp (standard error (SE): 4.05 bp), mean controls: 541.5 bp (SE: 2.02 bp), logistic regression p value = 2.13 × 10-5]. CONCLUSION: Increased genotypically-estimated LTL was significantly associated with increased meningioma risk. A role for telomere length in the pathophysiology of meningioma is novel, and could lead to new insights on the etiology of meningioma.


Assuntos
Leucócitos/patologia , Neoplasias Meníngeas/etiologia , Meningioma/etiologia , Polimorfismo de Nucleotídeo Único , Homeostase do Telômero , Estudos de Casos e Controles , Feminino , Seguimentos , Genótipo , Humanos , Leucócitos/metabolismo , Masculino , Neoplasias Meníngeas/patologia , Meningioma/patologia , Prognóstico , Fatores de Risco
7.
Cancer Res ; 79(8): 2065-2071, 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30709929

RESUMO

Genome-wide association studies (GWAS) have so far identified 25 loci associated with glioma risk, with most showing specificity for either glioblastoma (GBM) or non-GBM tumors. The majority of these GWAS susceptibility variants reside in noncoding regions and the causal genes underlying the associations are largely unknown. Here we performed a transcriptome-wide association study to search for novel risk loci and candidate causal genes at known GWAS loci using Genotype-Tissue Expression Project (GTEx) data to predict cis-predicted gene expression in relation to GBM and non-GBM risk in conjunction with GWAS summary statistics on 12,488 glioma cases (6,183 GBM and 5,820 non-GBM) and 18,169 controls. Imposing a Bonferroni-corrected significance level of P < 5.69 × 10-6, we identified 31 genes, including GALNT6 at 12q13.33, as a candidate novel risk locus for GBM (mean Z = 4.43; P = 5.68 × 10-6). GALNT6 resides at least 55 Mb away from any previously identified glioma risk variant, while all other 30 significantly associated genes were located within 1 Mb of known GWAS-identified loci and were not significant after conditioning on the known GWAS-identified variants. These data identify a novel locus (GALNT6 at 12q13.33) and 30 genes at 12 known glioma risk loci associated with glioma risk, providing further insights into glioma tumorigenesis. SIGNIFICANCE: This study identifies new genes associated with glioma risk, increasing understanding of how these tumors develop.

8.
Neuro Oncol ; 21(4): 451-461, 2019 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-30624711

RESUMO

BACKGROUND: Twenty-five single nucleotide polymorphisms (SNPs) are associated with adult diffuse glioma risk. We hypothesized that the inclusion of these 25 SNPs with age at diagnosis and sex could estimate risk of glioma as well as identify glioma subtypes. METHODS: Case-control design and multinomial logistic regression were used to develop models to estimate the risk of glioma development while accounting for histologic and molecular subtypes. Case-case design and logistic regression were used to develop models to predict isocitrate dehydrogenase (IDH) mutation status. A total of 1273 glioma cases and 443 controls from Mayo Clinic were used in the discovery set, and 852 glioma cases and 231 controls from UCSF were used in the validation set. All samples were genotyped using a custom Illumina OncoArray. RESULTS: Patients in the highest 5% of the risk score had more than a 14-fold increase in relative risk of developing an IDH mutant glioma. Large differences in lifetime absolute risk were observed at the extremes of the risk score percentile. For both IDH mutant 1p/19q non-codeleted glioma and IDH mutant 1p/19q codeleted glioma, the lifetime risk increased from almost null to 2.3% and almost null to 1.7%, respectively. The SNP-based model that predicted IDH mutation status had a validation concordance index of 0.85. CONCLUSIONS: These results suggest that germline genotyping can provide new tools for the initial management of newly discovered brain lesions. Given the low lifetime risk of glioma, risk scores will not be useful for population screening; however, they may be useful in certain clinically defined high-risk groups.

9.
Cancer Causes Control ; 30(2): 177-185, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30560391

RESUMO

PURPOSE: Previous studies have suggested an association between relative leukocyte telomere length (rLTL) and glioma risk. This association may be influenced by several factors, including allergies, BMI, and smoking. Previous studies have shown that individuals with asthma and allergy have shortened relative telomere length, and decreased risk of glioma. Though, the details and the interplay between rLTL, asthma and allergies, and glioma molecular phenotype is largely unknown. METHODS: rLTL was measured by qPCR in a Swedish population-based glioma case-control cohort (421 cases and 671 controls). rLTL was related to glioma risk and health parameters associated with asthma and allergy, as well as molecular events in glioma including IDH1 mutation, 1p/19q co-deletion, and EGFR amplification. RESULTS: Longer rLTL was associated with increased risk of glioma (OR = 1.16; 95% CI 1.02-1.31). Similar to previous reports, there was an inverse association between allergy and glioma risk. Specific, allergy symptoms including watery eyes was most strongly associated with glioma risk. High body mass index (BMI) a year prior diagnosis was significantly protective against glioma in our population. Adjusting for allergy, asthma, BMI, and smoking did not markedly change the association between longer rLTL and glioma risk. rLTL among cases was not associated with IDH1 mutation, 1p/19q co-deletion, or EGFR amplification, after adjusting for age at diagnosis and sex. CONCLUSIONS: In this Swedish glioma case-control cohort, we identified that long rLTL increases the risk of glioma, an association not confounded by allergy, BMI, or smoking. This highlights the complex interplay of the immune system, rLTL and cancer risk.


Assuntos
Neoplasias Encefálicas/epidemiologia , Glioma/epidemiologia , Leucócitos , Telômero , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Neoplasias Encefálicas/genética , Estudos de Casos e Controles , Fatores de Confusão (Epidemiologia) , Feminino , Glioma/genética , Humanos , Hipersensibilidade/epidemiologia , Masculino , Pessoa de Meia-Idade , Fenótipo , Fatores de Risco , Fumar/epidemiologia , Suécia/epidemiologia
10.
Artigo em Inglês | MEDLINE | ID: mdl-30482874

RESUMO

BACKGROUND: There have been few studies of sufficient size to address the relationship between glioma risk and the use of aspirin or non-steroidal anti-inflammatory drugs (NSAIDs), and results have been conflicting. The purpose of this study was to examine the associations between glioma and aspirin/NSAID use, and to aggregate these findings with prior published studies using meta-analysis. METHODS: The Glioma International Case-Control Study (GICC) consists of 4,533 glioma cases and 4,171 controls recruited from 2010-2013. Interviews were conducted using a standardized questionnaire to obtain information on aspirin/NSAID use. We examined history of regular use for >=6 months and duration-response. Restricted maximum likelihood meta-regression models were used to aggregate site-specific estimates, and to combine GICC estimates with previously published studies. RESULTS: A history of daily aspirin use for >=6 months was associated with a 38% lower glioma risk, compared to not having a history of daily use (adjusted meta-OR=0.62, 95% CI=0.54-0.70). There was a significant duration-response trend (p=1.67x10-17), with lower ORs for increasing duration of aspirin use. Duration-response trends were not observed for NSAID use. In the meta-analysis aggregating GICC data with five previous studies, there was a marginally significant association between use of aspirin and glioma (mOR=0.84, 95% CI=0.70-1.02), but no association for NSAID use. CONCLUSION: Our study suggests that aspirin may be associated with a reduced risk of glioma. IMPACT: These results imply that aspirin use may be associated with decreased glioma risk. Further research examining the association between aspirin use and glioma risk is warranted.

11.
Prev Med ; 118: 309-316, 2018 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-30419254

RESUMO

Mexican-origin adolescents have a high prevalence of obesity. Research is needed to understand how family context may shape adolescent BMI. This study examined longitudinal associations of family functioning variables with the Centers for Disease Control and Prevention's modified BMI z-score (BMIaz) in 1175 Mexican-origin adolescents, and explored interactions with acculturation. Adolescents (50% female, aged 11-13 y in 2005-06) were identified from an ongoing cohort study of Mexican-origin adults in Houston, TX, and were assessed three times from 2005-06 to 2010-11. In multivariate linear mixed models stratified by gender, we assessed longitudinal associations of family cohesion and family conflict with adolescent BMIaz and explored interactions with language acculturation. We disaggregated the between- (mean) and within-person (individual deviation) components of family cohesion and family conflict to assess the effects on BMIaz. Approximately one-third of adolescents were obese at baseline, and BMIaz declined during the study. In girls, higher mean family cohesion and conflict were associated with steeper declines in BMIaz. Parental linguistic acculturation modified the relationship between within-person deviation in family cohesion and BMIaz in girls, such that high parental U.S. acculturation was associated with a stronger inverse association. There were no significant associations in boys. These findings highlight the potential importance of the family context to female adolescent BMI and the promise of addressing family context in obesity-related interventions.

12.
Am J Cancer Res ; 8(9): 1775-1787, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30323970

RESUMO

OBJECTIVES: The composition and structure of site-specific microbiota have been investigated as potential biomarkers for a variety of chronic inflammatory diseases and cancers. While many studies have focused on the changes in the airway microbiota using respiratory specimens from patients with various respiratory diseases, more research is needed to explore the microbial profiles within the distal lung parenchyma in smokers with lung cancer and/or emphysema. MATERIALS AND METHODS: To describe and contrast lung tissue-associated microbial signatures in smokers with lung cancer and/or emphysema, we employed culture-independent pyrosequencing of 16S rRNA gene hypervariable V4 region and compositional analysis in non-malignant lung tissue samples obtained from 40 heavy smokers, including 10 emphysema-only, 11 lung cancer-only, and 19 with both lung cancer and emphysema. RESULTS AND CONCLUSION: The emphysema-only group presented a lower bacterial community evenness defined by a significantly lower Shannon diversity index compared to the lung cancer patients with or without emphysema (P = 0.006). Furthermore, community compositions of lung cancer patients with or without emphysema were characterized by a significantly lower abundance of Proteobacteria (primary the genera Acinetobacter and Acidovorax) and higher prevalence of Firmicutes (Streptococcus) and Bacteroidetes (Prevotella), compared to emphysema-only patients. In conclusion, the lung microbial composition and communities structures of smokers with lung cancer are distinct from the emphysema-only patients. Although preliminary, our findings suggest that lung microbiome changes could be a biomarker of lung cancer that could eventually be used to help screening for the disease.

13.
PLoS One ; 13(9): e0204372, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30248155

RESUMO

BACKGROUND: To date, studies on inflammatory breast cancer (IBC) lack comprehensive epidemiological data. We analyzed detailed prospectively collected clinical and epidemiological data from the IBC Registry at The University of Texas MD Anderson Cancer Center. METHODS: Patients with IBC (n = 248) were consecutively diagnosed and prospectively enrolled between November 2006 and April 2013. All patients were newly diagnosed and at least 18 years old. Secondary IBC was excluded. Overall 160 variables were collected and evaluated including sociodemographics, anthropometrics, tobacco and alcohol consumption, reproductive variables, and family history data. RESULTS: Mean age at diagnosis was 51.6 (±11.5 SD) years, and the majority of patients were White (77.8%). A mean BMI ≥ 25 kg/m2, irrespective of menopausal status, was observed in 80.2% of all patients, with 82.6% of African Americans being obese. Approximately 42.2% of patients were ever smokers, and 91% reported ever being pregnant. A history of breastfeeding was reported in 54% of patients, with significant differences between ethnic groups in favor of White women (P<0.0001). Other reproductive factors such as use of birth control pills & hormone replacement therapy were also more frequently associated with White women compare to other ethnic groups (P < 0.05). In the multivariate Cox proportional hazard analysis, African American or Hispanic ethnicity, not having breastfed, higher clinical stage, and TNBC subtype were associated with shorter survival. CONCLUSION: Our data suggest that IBC is associated with distinct epidemiological profiles. This information could assist in targeting patients with specific preventive strategies based on their modifiable behavioral patterns.

14.
Neuro Oncol ; 2018 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-30124908

RESUMO

Background: To date, genome-wide association studies (GWAS) have identified 25 risk variants for glioma, explaining 30% of heritable risk. Most histologies occur with significantly higher incidence in males, and this difference is not explained by currently-known risk factors. A previous GWAS identified sex-specific glioma risk variants, and this analysis aims to further elucidate risk variation by sex using gene- and pathway-based approaches. Methods: Results from the Glioma International Case-Control Study were used as a testing set, and results from three GWAS were combined via meta-analysis and used as a validation set. Using summary statistics for nominally significant autosomal SNPs (p<0.01 in a previous meta-analysis) and nominally significant X-chromosome SNPs (p<0.01), three algorithms (Pascal, BimBam, and GATES) were used to generate gene-scores, and Pascal was used to generate pathway-scores. Results were considered statistically significant in the discovery set when p<3.3x10-6 and in the validation set when p<0.001 in 2/3 algorithms. Results: 25 genes within 5 regions and 19 genes within 6 regions reached statistical significance in at least 2/3 algorithms in males and females, respectively. EGFR was significantly associated with all glioma and glioblastoma in males only, and a female-specific association in TERT, all of which remained nominally significant after conditioning on known risk loci. There were nominal associations with the Biocarta telomeres pathway in both males and females. Conclusions: These results provide additional evidence that there may be differences by sex in genetic risk for glioma. Additional analyses may further elucidate the biological processes through which this risk is conferred.

15.
Int J Cancer ; 143(10): 2359-2366, 2018 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-30152087

RESUMO

Glioblastoma (GBM) is the most common malignant brain tumor in the United States. Incidence of GBM increases with age, and younger age-at-diagnosis is significantly associated with improved prognosis. While the relationship between candidate GBM risk SNPs and age-at-diagnosis has been explored, genome-wide association studies (GWAS) have not previously been stratified by age. Potential age-specific genetic effects were assessed in autosomal SNPs for GBM patients using data from four previous GWAS. Using age distribution tertiles (18-53, 54-64, 65+) datasets were analyzed using age-stratified logistic regression to generate p values, odds ratios (OR), and 95% confidence intervals (95%CI), and then combined using meta-analysis. There were 4,512 total GBM cases, and 10,582 controls used for analysis. Significant associations were detected at two previously identified SNPs in 7p11.2 (rs723527 [p54-63 = 1.50x10-9 , OR54-63 = 1.28, 95%CI54-63 = 1.18-1.39; p64+ = 2.14x10-11 , OR64+ = 1.32, 95%CI64+ = 1.21-1.43] and rs11979158 [p54-63 = 6.13x10-8 , OR54-63 = 1.35, 95%CI54-63 = 1.21-1.50; p64+ = 2.18x10-10 , OR64+ = 1.42, 95%CI64+ = 1.27-1.58]) but only in persons >54. There was also a significant association at the previously identified lower grade glioma (LGG) risk locus at 8q24.21 (rs55705857) in persons ages 18-53 (p18-53 = 9.30 × 10-11 , OR18-53 = 1.76, 95%CI18-53 = 1.49-2.10). Within The Cancer Genome Atlas (TCGA) there was higher prevalence of 'LGG'-like tumor characteristics in GBM samples in those 18-53, with IDH1/2 mutation frequency of 15%, as compared to 2.1% [54-63] and 0.8% [64+] (p = 0.0005). Age-specific differences in cancer susceptibility can provide important clues to etiology. The association of a SNP known to confer risk for IDH1/2 mutant glioma and higher prevalence of IDH1/2 mutation within younger individuals 18-53 suggests that more younger individuals may present initially with 'secondary glioblastoma.'

16.
Neuro Oncol ; 20(12): 1625-1633, 2018 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-30165405

RESUMO

Background: The genomic characterization of sporadically arising gliomas has delineated molecularly and clinically distinct subclasses of disease. However, less is known about the molecular nature of gliomas that are familial in origin. We performed molecular subtyping of 163 tumor specimens from individuals with a family history of glioma and integrated germline and somatic genomic data to characterize the pathogenesis of 20 tumors in additional detail. Methods: Immunohistochemical analyses were performed on formalin-fixed, paraffin-embedded tumor sections to determine molecular subtypes of glioma. For 20 cases, tumor DNA was exome sequenced on an Illumina HiSeq 2000 platform and copy number profiling was performed on the Illumina HumanOmniExpress BeadChip. Genotypes at glioma risk polymorphisms were determined from germline DNA profiled on the Illumina Infinium OncoArray and deleterious germline mutations were identified from germline sequencing data. Results: All 3 molecular subtypes of sporadic glioma were represented in the overall case series, including molecular glioblastoma (n = 102), oligodendroglioma (n = 21), and astrocytoma (n = 20). Detailed profiling of 20 of these cases showed characteristic subtype-specific alterations at frequencies comparable to sporadic glioma cases. All 20 cases had alterations in genes regulating telomere length. Frequencies of common glioma risk alleles were similar to those among sporadic cases, and correlations between risk alleles and same-gene somatic mutations were not observed. Conclusions: This study illustrates that the molecular characteristics of familial tumors profiled largely recapitulate what is known about sporadic glioma and that both germline and somatic molecular features target common core pathways involved in gliomagenesis. Key Points: 1. Familial and sporadic gliomas display highly comparable molecular landscapes. 2. Germline and somatic molecular events target common core pathways involved in gliomagenesis. 3. Carriage of germline glioma risk variants is not associated with somatic events in the same gene.

17.
Sci Rep ; 8(1): 7352, 2018 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-29743610

RESUMO

Incidence of glioma is approximately 50% higher in males. Previous analyses have examined exposures related to sex hormones in women as potential protective factors for these tumors, with inconsistent results. Previous glioma genome-wide association studies (GWAS) have not stratified by sex. Potential sex-specific genetic effects were assessed in autosomal SNPs and sex chromosome variants for all glioma, GBM and non-GBM patients using data from four previous glioma GWAS. Datasets were analyzed using sex-stratified logistic regression models and combined using meta-analysis. There were 4,831 male cases, 5,216 male controls, 3,206 female cases and 5,470 female controls. A significant association was detected at rs11979158 (7p11.2) in males only. Association at rs55705857 (8q24.21) was stronger in females than in males. A large region on 3p21.31 was identified with significant association in females only. The identified differences in effect of risk variants do not fully explain the observed incidence difference in glioma by sex.

18.
PLoS One ; 13(5): e0197408, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29763473

RESUMO

BACKGROUND: There is evidence that maternal genotypes in folate-related genes are associated with pediatric acute lymphoblastic leukemia (ALL) independent of offspring genotype. We evaluated the relationship between maternal genotypes in methionine synthase (MTR) and DNA methylation status in ALL to better characterize the molecular mechanism underlying this association. PROCEDURE: We obtained bone marrow samples from 51 patients with ALL at diagnosis and from 6 healthy donors. Mothers of patients provided a saliva sample and were genotyped at 11 tagSNPs in MTR. DNA methylation was measured in bone marrow mononuclear cells of patients and six healthy marrow donors. We used hierarchical clustering to identify patients with a hypermethylator phenotype based on 281 differentially methylated promoter CpGs. We used logistic regression to estimate the effects of maternal genotype on the likelihood of DNA hypermethylation in ALL and Ingenuity Pathway Analysis to identify networks enriched for differentially methylated genes. RESULTS: Twenty-two cases (43%) demonstrated promoter hypermethylation, which was more frequent among those with ETV6-RUNX1 fusion and initial white blood cell count < 50 x 109/L. Maternal rs12759827 was associated with aberrant DNA methylation (odds ratio [OR] 4.67, 95% confidence interval 1.46-16.31); non-significantly elevated ORs were observed for all other SNPs. Aberrantly methylated promoter CpGs aligned to genes with known cancer-related functions. DISCUSSION: Maternal folate metabolic genotype may be associated with DNA methylation patterns in ALL in their offspring. Therefore, the effect of maternal genotypes on ALL susceptibility may act through aberrant promoter methylation, which may contribute to the in utero origins of ALL.


Assuntos
Metilação de DNA/genética , Polimorfismo de Nucleotídeo Único/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Criança , Pré-Escolar , Feminino , Genótipo , Humanos , Lactente , Modelos Logísticos , Masculino
19.
J Neurol ; 265(6): 1432-1442, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29687214

RESUMO

BACKGROUND: The purpose of this study was to evaluate the distribution of glioma-related seizures and seizure control at the time of tumor diagnosis with respect to tumor histologic subtypes, tumor treatment and patient characteristics, and to compare seizure history preceding tumor diagnosis (or study enrollment) between glioma patients and healthy controls. METHODS: The Glioma International Case Control study (GICC) risk factor questionnaire collected information on demographics, past medical/medication history, and occupational history. Cases from eight centers were also asked detailed questions on seizures in relation to glioma diagnosis; cases (n = 4533) and controls (n = 4171) were also asked about seizures less than 2 years from diagnosis and previous seizure history more than 2 years prior to tumor diagnosis, including childhood seizures. RESULTS: Low-grade gliomas (LGGs), particularly oligodendrogliomas/oligoastrocytomas, had the highest proportion of glioma-related seizures. Patients with low-grade astrocytoma demonstrated the most medically refractory seizures. A total of 83% of patients were using only one antiepileptic drug (AED), which was levetiracetam in 71% of cases. Gross total resection was strongly associated with reduced seizure frequency (p < 0.009). No significant difference was found between glioma cases and controls in terms of seizure occurring more than 2 years before diagnosis or during childhood. CONCLUSIONS: Our study showed that glioma-related seizures were most common in low-grade gliomas. Gross total resection was associated with lower seizure frequency. Additionally, having a history of childhood seizures is not a risk factor ***for developing glioma-related seizures or glioma.


Assuntos
Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/patologia , Glioma/complicações , Glioma/patologia , Convulsões/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/fisiopatologia , Estudos de Casos e Controles , Feminino , Glioma/epidemiologia , Glioma/fisiopatologia , Humanos , Internacionalidade , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estudos Retrospectivos , Convulsões/epidemiologia , Convulsões/patologia , Convulsões/fisiopatologia , Inquéritos e Questionários , Adulto Jovem
20.
Artigo em Inglês | MEDLINE | ID: mdl-29679333

RESUMO

PURPOSE: Independent and combined effects of air pollution and psychosocial stressors on hypertension, a risk factor for cardiovascular disease, among Hispanics are not well studied. METHODS: We administered a pilot-tested questionnaire on individual- and neighborhood-level psychosocial stressors, developed with community input, to nearly 2500 individuals from the MD Anderson Cancer Center cohort of Mexican-Americans. We used data from local air quality monitors to estimate individual exposures to ozone (O3) and fine particulate matter (PM2.5) for the 12-month period preceding enrollment using inverse distance interpolation. We applied logistic regression models to examine relationships between exposures to psychosocial stressors and air pollution with prevalent hypertension and used stratified analyses to examine the interacting effects of these two exposures on hypertension. RESULTS: There was a positive association between prevalent hypertension and a high frequency of feeling anxious or depressed (prevalence odds ratio (POR) = 1.36, 95% CI [1.06-1.75]) and experiencing aches and pains (POR = 1.29, 95% CI [1.01-1.64]). The odds of having hypertension were also elevated among those worrying about their own health (POR = 1.65, 95% CI [1.30-2.06]) or about not having enough money (POR = 1.27, 95% CI [1.01-1.6]). We observed an inverse association between O3 and hypertension. There was no interaction between psychosocial stressors and O3 on hypertension. CONCLUSION: Our findings add to the evidence of a positive association between individual and family stressors on hypertension among Hispanics and other racial/ethnic groups. Contrary to previous studies reporting positive associations, our results suggest that long-term exposure to O3 may be inversely related to prevalent hypertension.

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