There is evidence that exposure to chlorinated solvents may be associated with childhood medulloblastoma and primitive neuroectodermal tumor (M/PNET) risk. Animal models suggest genes related to detoxification and DNA repair are important in the carcinogenicity of these pollutants, however, there have been no human studies assessing the modifying effects of these genotypes on the association between chlorinated solvents and childhood M/PNET risk.
We conducted a case-only study to evaluate census tract-level exposure to chlorinated solvents and the risk of childhood M/PNET in the context of detoxification and DNA repair genotypes. Cases (n = 98) were obtained from Texas Children’s Hospital and MD Anderson Cancer Center. Key genotypes (n = 22) were selected from the Illumina Human 1M Quad SNP Chip. Exposure to chlorinated solvents (methylene chloride, perchloroethylene, trichloroethylene, and vinyl chloride) was estimated from the U.S. EPA’s 1999 Assessment System for Population Exposure Nationwide (ASPEN). Logistic regression was used to estimate the case-only odds ratios and 95% confidence intervals (CIs).
There were 11 significant gene-environment interactions associated with childhood M/PNET risk. However, after correcting for multiple comparisons, only the interaction between high trichloroethylene levels and OGG1 rs293795 significantly increased the risk of childhood M/PNET risk (OR = 9.24, 95% CI: 2.24, 38.24, Q = 0.04).
This study provides an initial assessment of the interaction between ambient levels of chlorinated solvents and potentially relevant genotypes on childhood M/PNET risk. Our results are exploratory and must be validated in animal models, as well as additional human studies.
Hazardous air pollutants; chlorinated solvents; DNA repair genes; detoxification genes; childhood medulloblastoma and primitive neuroectodermal tumor
Ionizing radiation is a consistently identified and potentially modifiable risk factor for meningioma, the most frequently reported primary brain tumor in the United States.
To examine the association between dental x-rays, the most common artificial source of ionizing radiation, and risk of intra-cranial meningioma.
Design and Setting
Population-based case-control study design.
The study includes 1433 intra-cranial meningioma cases aged 29-79 years diagnosed among residents of the states of Connecticut, Massachusetts, North Carolina, the San Francisco Bay Area and eight Houston, Texas counties between May 1, 2006 and April 28, 2011 and 1350 controls that were frequency-matched on age, sex and geography.
Main Outcome Measure
The association of intra-cranial meningioma diagnosis with self-report of bitewing, full-mouth, and panorex dental x-rays.
Over a lifetime, cases were more than twice (Odds ratio (OR) = 2.0, 95% confidence interval (CI), 1.4-2.9) as likely as controls to report having ever had a bitewing exam. Regardless of the age at which the films were received, persons who reported receiving bitewing films on a yearly or greater frequency had an elevated risk with odds ratios of 1.4 (95%CI: 1.0-1.8), 1.6 (95%CI: 1.2-2.0), 1.9 (95%CI: 1.4-2.6), and 1.5 (95%CI: 1.1-2.0) for ages <10, 10-19, 20-49, and 50+ years, respectively. Increased risk of meningioma was also associated with panorex films taken at a young age or on a yearly or greater frequency with persons reporting receiving such films under the age of 10 years at 4.9 times (95%CI: 1.8-13.2) increased risk of meningioma. No association was appreciated with location of tumor above or below the tentorium.
Exposure to some dental x-rays performed in the past, when radiation exposure was greater than in the current era, appears to be associated with increased risk of intra-cranial meningioma. As with all sources of artificial ionizing radiation, considered use of this modifiable risk factor may be of benefit to patients.
cancer; dental x-rays; epidemiology; ionizing radiation; meningioma; computed tomography; population-based; DNA repair genes; risk factors; brain tumor; genetics; diagnostic x-rays
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 casecontrol 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 risk of glioma has consistently been shown to be increased two-fold in relatives of patients with primary brain tumors (PBT). A recent genome-wide linkage study of glioma families provided evidence for a disease locus on 17q12-21.32, with the possibility of four additional risk loci at 6p22.3, 12p13.33-12.1, 17q22-23.2, and 18q23.
To identify the underlying genetic variants responsible for the linkage signals, we compared the genotype frequencies of 5,122 SNPs mapping to these five regions in 88 glioma cases with and 1,100 cases without a family history of PBT (discovery study). An additional series of 84 familial and 903 non-familial cases were used to replicate associations.
In the discovery study, 12 SNPs showed significant associations with family history of PBT (P < 0.001). In the replication study, two of the 12 SNPs were confirmed: 12p13.33-12.1 PRMT8 rs17780102 (P = 0.031) and 17q12-21.32 SPOP rs650461 (P = 0.025). In the combined analysis of discovery and replication studies, the strongest associations were attained at four SNPs: 12p13.33-12.1 PRMT8 rs17780102 (P = 0.0001), SOX5 rs7305773 (P = 0.0001) and STKY1 rs2418087 (P = 0.0003), and 17q12-21.32 SPOP rs6504618 (P = 0.0006). Further, a significant gene-dosage effect was found for increased risk of family history of PBT with these four SNPs in the combined data set (Ptrend < 1.0 ×10−8).
The results support the linkage finding that some loci in the 12p13.33-12.1 and 17q12-q21.32 may contribute to gliomagenesis and suggest potential target genes underscoring linkage signals.
Association; Polymorphisms; Glioma; Family history of primary brain tumor; Linkage analysis
Genome-wide sequencing identified heterozygous, constitutional, Ataxia telangiectaisa mutated (ATM) gene mutations in two kindreds with familial pancreatic cancer. Mutations segregated with disease in both kindreds and tumor analysis demonstrated LOH of the wildtype allele. Sequence analysis of an additional 166 familial pancreatic cancer probands indentified four additional patients with deleterious mutations in the ATM gene, while no deleterious mutations were identified in 190 spouse controls (p=0.046). These results indicate that ATM mutations play an important role in familial pancreatic cancer predisposition.
ATM; predisposition; familial; pancreas; cancer
A number of studies have reported on the association between smoking and meningioma risk, with inconsistent findings. We examined the effect of gender on the association between cigarette smoking and risk of intra-cranial meningioma in a large population-based, case-control study.
The data includes 1433 intra-cranial meningioma cases aged 29–79 years diagnosed among residents of the states of Connecticut, Massachusetts, North Carolina, the San Francisco Bay Area and eight Texas counties between May 1, 2006 and April 28, 2011 and 1349 controls that were frequency-matched on age, sex and geography. The data are analyzed separately and in a meta-analysis with six previously reported studies.
Female cases who reported having ever smoked were at significantly decreased risk of intra-cranial meningioma (Odds ratio (OR) = 0.8, 95% confidence interval (CI), 0.7–0.9) in contrast to male cases who were at increased risk (OR:1.3, 95%CI: 1.0–1.7). Similar findings were noted for current and past smokers. Smoking-induced risk for females did not vary by menopausal status. For males, increased duration of use (p = 0.04) as well as increasing number of pack-years (p = 0.02) was associated with elevated risk. A meta-analysis including 2614 cases and 1,179,686 controls resulted in an OR for ever smoking of 0.82 (95%CI: 0.68–0.98) for women and 1.39 (95%CI: 1.08–1.79) for men.
The association of cigarette smoking and meningioma case status varies significantly by gender with women at reduced risk and men at greater risk.
Whether the observed differences are associated with a hormonal etiology will require additional investigation.
Meningioma; epidemiology; meta-analysis; sex; genetics; smoking; cigarettes; gender; hormones
The role of human cytomegalovirus (HCMV) in glioma development and progression remains controversial. The purpose of our study was to assess the potential associations between anti-HCMV antibodies (immunoglobulin G [IgG] and immunoglobulin M [IgM]) and glioma risk and prognosis using data from the Harris County Case–Control Study. Multivariable logistic regression models were utilized to estimate odds ratios and 95% confidence intervals (CI) for the associations between glioma status and antibody levels among glioma cases (n = 362) and cancer-free controls (n = 462). Hazard ratios and 95% CIs were calculated using Cox proportional hazards regression, adjusting for age, race, and sex, to determine if antibody levels were associated with survival over time among cases. Among IgG-positive participants, increasing anti-HCMV IgG levels were associated with decreasing glioma risk (P for trend = 0.0008), and those with the lowest level of anti-HCMV IgG (<10 U/mL) had the highest glioma risk, controlling for age, sex, and race/ethnicity (OR: 2.51, 95% CI: 1.42–4.43). Antibody levels were not associated with survival among glioma cases. Our study contributes new evidence toward the potential importance of the direct and indirect effects of HCMV infection in gliomagenesis.
Brain neoplasms; glioma; human cytomegalovirus; immunoglobulin G; immunoglobulin M; risk factors
Established psychosocial risk factors increase the risk for experimentation among Mexican-origin youth. Now we comprehensively investigate the added contribution of select polymorphisms in candidate genetic pathways associated with sensation seeking, risk taking, and smoking phenotypes to predict experimentation.
Participants, (N=1,118 Mexican origin youth) recruited from a large population-based cohort study in Houston, Texas, provided prospective data on cigarette experimentation over three years. Psychosocial data were elicited twice—baseline and final follow-up. Participants were genotyped for 672 functional and tagging variants in the dopamine, serotonin and opioid pathways.
After adjusting for gender and age, with a Bayesian False Discovery Probability set at 0.8 and prior probability of 0.05, six gene variants were significantly associated with risk of experimentation. After controlling for established risk factors, multivariable analyses revealed that participants with six or more risk alleles were 2.25 (95%CI: 1.62–3.13) times more likely to have experimented since baseline compared to participants with five or fewer. Among committed never smokers (N=872), three genes (OPRM1, SNAP25, HTR1B) were associated with experimentation as were all psychosocial factors. Among susceptible youth (N=246) older age at baseline, living with a smoker, and three different genes (HTR2A, DRD2, SLC6A3) predicted experimentation.
Our findings, which have implications for development of culturally-specific interventions, need to be validated in other ethnic groups.
These results suggest that variations in select genes interact with a cognitive predisposition toward smoking. In susceptible adolescents, the impact of the genetic variants appears to be larger compared to committed never smokers.
Hypersensitivity to radiation exposure has been suggested to be a risk factor for the development of breast cancer. In this case–control study of 515 young women (≤55 years) with newly diagnosed sporadic breast cancer and 402 cancer-free controls, we examined the radiosensitivity as measured by the frequency of chromatid breaks induced by gamma-radiation exposure in the G2 phase of phytohemagglutinin-stimulated and short-term cultured fresh lymphocytes. We found that the average chromatid breaks per cell from 50 well-spread metaphases were statistically significantly higher in 403 non-Hispanic White breast cancer patients (0.52 ± 0.22) than that in 281 non-Hispanic White controls (0.44 ± 0.16) (P value < 0.001), and in 60 Mexican American breast cancer patients (0.52 ± 0.19) than that in 65 Mexican American controls (0.44 ± 0.16) (P value = 0.021), but the difference was not significant in African Americans (52 cases [0.45 ± 0.16] versus 56 controls [0.47 ± 0.16], P = 0.651). The frequency of chromatid breaks per cell above the median of control subjects was associated with two-fold increased risk for breast cancer in non-Hispanic Whites and Mexican Americans. A dose–response relationship was evident between radiosensitivity and risk for breast cancer (Ptrend < 0.001) in these two ethnic groups. We concluded that gamma-ray-induced mutagen sensitivity may play a role in susceptibility to breast cancer in young non-Hispanic White and Mexican American women.
Radiation; Chromosomal instability; Breast neoplasm; Molecular epidemiology
Gliomas, which generally have a poor prognosis, are the most common primary malignant brain tumors in adults. Recent genome-wide association studies have demonstrated that inherited susceptibility plays a role in the development of glioma. Although first-degree relatives of patients exhibit a two-fold increased risk of glioma, the search for susceptibility loci in familial forms of the disease has been challenging because the disease is relatively rare, fatal, and heterogeneous, making it difficult to collect sufficient biosamples from families for statistical power. To address this challenge, the Genetic Epidemiology of Glioma International Consortium (Gliogene) was formed to collect DNA samples from families with two or more cases of histologically confirmed glioma. In this study, we present results obtained from 46 U.S. families in which multipoint linkage analyses were undertaken using nonparametric (model-free) methods. After removal of high linkage disequilibrium SNPs, we obtained a maximum nonparametric linkage score (NPL) of 3.39 (P=0.0005) at 17q12–21.32 and the Z-score of 4.20 (P=0.000007). To replicate our findings, we genotyped 29 independent U.S. families and obtained a maximum NPL score of 1.26 (P=0.008) and the Z-score of 1.47 (P=0.035). Accounting for the genetic heterogeneity using the ordered subset analysis approach, the combined analyses of 75 families resulted in a maximum NPL score of 3.81 (P=0.00001). The genomic regions we have implicated in this study may offer novel insights into glioma susceptibility, focusing future work to identify genes that cause familial glioma.
Glioma; family studies; linkage; haplotype pattern; NPL
Little is known about the epidemiology of meningioma, the most frequently reported primary brain tumor in the US. The authors undertook a case-control study to examine the relationship between family and personal medical history and meningioma risk.
The authors compared the personal and first-degree family histories of 1124 patients with meningioma (age range 20–79 years) in Connecticut, Massachusetts, North Carolina, the San Francisco Bay Area, and 8 Houston counties between May 1, 2006, and February 26, 2010, and the histories of 1000 control individuals who were frequency-matched for age, sex, and geography.
The patients were more likely than the controls to report a first-degree family history of meningioma (OR 4.4, 95% CI 1.6–11.5), and there was an even stronger association in younger cases. The patients were less likely than controls to report immune conditions including allergy (OR 0.6, 95% CI 0.5–0.7) but were more likely to report a history of thyroid cancer (OR 4.7, 95% CI 1.02–21.5) or leukemia (OR 5.4, 95% CI 1.2–24.1) (most after radiotherapy). Among women, patients were more likely than controls to report hormonally related conditions—uterine fibroid tumors (OR 1.2, 95% CI 1.0–1.5), endometriosis (OR 1.5, 95% CI 1.5–2.1), and breast cancer (OR 1.4, 95% CI 0.8–2.3).
The influence of genetics, the immune system, and radiation near the head on meningioma risk is suggested in the authors’ findings; the role of hormones is intriguing but requires further study.
allergy; cancer; epidemiology; family history; hormones; immune factors; meningioma; radiation; oncology
The value of hormone receptor and human epidermal growth factor receptor 2 expression for predicting overall survival, distant relapse, and locoregional relapse was examined in patients with inflammatory breast cancer. Triple-negative disease was associated with worse outcomes, indicating the need for developing new locoregional and systemic treatment strategies for patients with this aggressive subtype.
Numerous studies have demonstrated that expression of estrogen/progesterone receptor (ER/PR) and human epidermal growth factor receptor (HER)-2 is important for predicting overall survival (OS), distant relapse (DR), and locoregional relapse (LRR) in early and advanced breast cancer patients. However, these findings have not been confirmed for inflammatory breast cancer (IBC), which has different biological features than non-IBC.
We retrospectively analyzed the records of 316 women who presented to MD Anderson Cancer Center in 1989–2008 with newly diagnosed IBC without distant metastases. Most patients received neoadjuvant chemotherapy, mastectomy, and postmastectomy radiation. Patients were grouped according to receptor status: ER+ (ER+/PR+ and HER-2−; n = 105), ER+HER-2+ (ER+/PR+ and HER-2+; n = 37), HER-2+ (ER−/PR− and HER-2+; n = 83), or triple-negative (TN) (ER−PR−HER-2−; n = 91). Kaplan–Meier and Cox proportional hazards methods were used to assess LRR, DR, and OS rates and their associations with prognostic factors.
The median age was 50 years (range, 24–83 years). The median follow-up time and median OS time for all patients were both 33 months. The 5-year actuarial OS rates were 58.7% for the entire cohort, 69.7% for ER+ patients, 73.5% for ER+HER-2+ patients, 54.0% for HER=2+ patients, and 42.7% for TN patients (p < .0001); 5-year LRR rates were 20.3%, 8.0%, 12.6%, 22.6%, and 38.6%, respectively, for the four subgroups (p < .0001); and 5-year DR rates were 45.5%, 28.8%, 50.1%, 52.1%, and 56.7%, respectively (p < .001). OS and LRR rates were worse for TN patients than for any other subgroup (p < .0001–.03).
TN disease is associated with worse OS, DR, and LRR outcomes in IBC patients, indicating the need for developing new locoregional and systemic treatment strategies for patients with this aggressive subtype.
Inflammatory breast cancer; Estrogen receptor; Progesterone receptor; HER-2; Molecular subtypes
Several studies have shown a decrease in glioma risk associated with a personal history of allergic conditions and the medications used to treat the symptoms. However, few studies have been able to examine risk within histological subgroups of glioma. Case-control data from M. D. Anderson Cancer Center and University of California, San Francisco were pooled to conduct the analysis stratified by histological subtype. A risk prediction model considering inflammation-related variables and antihistamine use was built using logistic regression. Of the subtypes examined, long-term antihistamine use was associated with increased risk of anaplastic gliomas, especially when length of use was considered in conjunction with history of asthma or allergy. Anaplastic cases with no history of asthma or allergy were 2.94 times more likely than controls to report antihistamine use for 10 years or more; while anaplastic cases with a history of asthma or allergy were 2.34 times more likely than controls to report antihistamine use for 10 years or more. Furthermore, anti-inflammatory medication use was associated with a protective effect against glioblastoma (OR=0.80; 95% CI: 0.65, 0.99), especially among individuals with no history of asthma or allergies. No statistically significant effects of anti-inflammatory drugs or antihistamines were evident for the other histological subtypes. Thus, modulation of the immune system by the use of common drugs, such as antihistamines or non-steroidal anti-inflammatory drugs, may contribute to the development of certain types of brain tumors.
glioma; glioblastoma; epidemiology; histamine antagonists; anti-inflammatory agents
Sitting time and sedentary behaviors have been associated with adverse health outcomes including obesity, diabetes and cardiovascular disease (CVD) within non- Hispanic White populations. Similar associations have not been described within Hispanic populations despite their high CVD risk profile. This study aimed to assess the association between sitting time and obesity, self-reported diagnosed diabetes, hypertension and high cholesterol among a large cohort (N=11,268) of Mexican origin adults and to assess whether obesity mediated these associations.
Using a cross-sectional design, data collected between 2004 and 2010 were analyzed in late 2010. Regression analyses evaluated associations between self-reported daily sitting hours and disease outcomes, controlling for demographics, employment status, family disease history, and light, moderate and strenuous physical activity.
Participants were mostly female (81.1%) Mexican origin adults. Sitting time was associated with increased odds of being obese, having diabetes and having hypertension, but not high cholesterol. Adjusted odds ratios of participants who reported sitting > 4 hours/day compared to those sitting 1-2 hours/day were for obesity OR=1.55 (95% CI 1.39, 1.73), p<.001, for diabetes OR=1.29 (95% CI, 1.09, 1.52), p=.003, for hypertension OR=1.17 (95% CI, 1.01, 1.37), p=.041. Associations controlled for physical activity and employment status. Effects on hypertension and diabetes were mediated by obesity.
Sitting time was significantly associated with detrimental health outcomes, independent of physical activity. Obesity mediated these relationships for diabetes and hypertension. Future research should assess whether interventions addressing sitting time are feasible and effective among Mexican origin populations.
Sitting time; Diabetes; Obesity; Hypertension; Hispanic
Meningioma, the most frequent tumor in the central nervous system, has few recognized risk factors. We explored the role of allergies in a population-based case-control consortium study of meningioma in five geographic areas. We also studied serum levels of a marker of atopic allergy (IgE) in a subset of study participants, a first for a study on meningioma. Participants (N = 1,065) with surgically resected, pathologically confirmed meningioma and controls (N = 634) selected via random-digit dialing were recruited and interviewed. Cases were less likely than controls to report history of physician-diagnosed allergy [odds ratio (OR) = 0.64; 95% confidence interval (95% CI): 0.51 – 0.80]. Also, cases (N = 295) had lower total serum IgE than controls [N = 192; OR = 0.85, 95% CI: 0.75–0.98 for each unit of Ln(IgE)]. Similar to glioma and cancers at several other sites, meningioma appears to have an inverse relationship with history of allergies and a biomarker of atopic allergy. Since some common opposing predisposition or developmental processes for allergy and meningioma may exist, further research into immune processes that can affect the incidence and natural history of meningioma is warranted.
Meningioma; epidemiology; risk factors; neurosurgery; brain tumor; genetics; immune factors
Objectives: Using a novel candidate SNP approach, we aimed to identify a possible genetic basis for the higher glioma incidence in Whites relative to East Asians and African-Americans. Methods: We hypothesized that genetic regions containing SNPs with extreme differences in allele frequencies across ethnicities are most likely to harbor susceptibility variants. We used International HapMap Project data to identify 3,961 candidate SNPs with the largest allele frequency differences in Whites compared to East Asians and Africans and tested these SNPs for association with glioma risk in a set of White cases and controls. Top SNPs identified in the discovery dataset were tested for association with glioma in five independent replication datasets. Results: No SNP achieved statistical significance in either the discovery or replication datasets after accounting for multiple testing or conducting meta-analysis. However, the most strongly associated SNP, rs879471, was found to be in linkage disequilibrium with a previously identified risk SNP, rs6010620, in RTEL1. We estimate rs6010620 to account for a glioma incidence rate ratio of 1.34 for Whites relative to East Asians. Conclusion: We explored genetic susceptibility to glioma using a novel candidate SNP method which may be applicable to other diseases with appropriate epidemiologic patterns.
glioma; candidate SNP association study; ancestry informative markers; admixture; race; ethnicity; brain cancer
Genome-wide association (GWA) studies, where hundreds of thousands of single-nucleotide polymorphisms (SNPs) are tested simultaneously, are becoming popular for identifying disease loci for common diseases. Most commonly, a GWA study involves two stages: the first stage includes testing the association between all SNPs and the disease and the second stage includes replication of SNPs selected from the first stage to validate associations in an independent sample. The first stage is considered to be more fundamental since the second stage is contingent on the results of the first stage. Selection of SNPs from stage one for genotyping in stage two is typically based on an arbitrary threshold or controlling type I errors. These strategies can be inefficient and have potential to exclude genotyping of disease-associated SNPs in stage two. We propose an approach for selecting top SNPs that uses a strategy based on the false-negative rate (FNR). Using the FNR approach, we proposed the number of SNPs that should be selected based on the observed p-values and a pre-specified multi-testing power in the first stage. We applied our method to simulated data and a GWA study of glioma (a rare form of brain tumor) data. Results from simulation and the glioma GWA indicate that the proposed approach provides an FNR-based way to select SNPs using pre-specified power.
False negative rate; SNP selection; Two-stage genome-wide association study
Neurocognitive impairment occurs in 20%-40% of childhood acute lymphoblastic leukemia (ALL) survivors, possibly mediated by folate depletion and homocysteine elevation following methotrexate treatment. We evaluated the relationship between folate pathway polymorphisms and neurocognitive impairment after childhood ALL chemotherapy.
Seventy-two childhood ALL survivors treated with chemotherapy alone underwent a neurocognitive battery consisting of: Trail Making Tests A (TMTA) and B (TMTB), Grooved Pegboard Test Dominant-Hand and Nondominant-Hand, Digit Span subtest, and Verbal Fluency Test. We performed genotyping for: 10-methylenetetrahydrofolate reductase (MTHFR 677C>T and MTHFR 1298A>C), serine hydroxymethyltransferase (SHMT 1420C>T), methionine synthase (MS 2756 A>G), methionine synthase reductase (MTRR 66A>G), and thymidylate synthase (TSER). Student's two sample t-test and analysis of covariance were used to compare test scores by genotype.
General impairment on the neurocognitive battery was related to MTHFR 1298A>C (p=0.03) and MS 2756A>G (p=0.05). Specifically, survivors with MTHFR 1298AC/CC genotypes scored, on average, 13 points lower on TMTB than those with MTHFR 1298AA genotype (p=0.001). The MS 2756AA genotype was associated with a 12.2 point lower mean TMTA score, compared to MS 2756 AG/GG genotypes (p=0.01). The TSER 2R/3R and 3R/3R genotypes were associated with an 11.4 point lower mean score on TMTB, compared to the TSER 2R/2R genotype (p=0.03). Survivors with >6 folate pathway risk alleles demonstrated a 9.5 point lower mean TMTA score (p=0.06) and 14.5 point lower TMTB score (p=0.002) than survivors with <6 risk alleles.
Folate pathway polymorphisms are associated with deficits in attention and processing speed after childhood ALL therapy.
folate; leukemia; neurocognitive; survivor
Understanding the factors that contribute to physical activity (PA) in Mexican-origin adolescents is essential to the design of effective efforts to enhance PA participation in this population.
Multivariable logistic regression was used to identify sociodemographic and behavioral correlates of self-reported PA in school and community settings in 1,154 Mexican-origin adolescents aged 12–17 years in Houston, TX.
The majority of adolescents were born in the US (74%), approximately half (51%) were overweight or obese, and nearly three-quarters (73%) watched more than 2 hours of weekday television. Similarities and differences by setting and gender were observed in the relationships between sociodemographic and behavioral characteristics and PA. In boys, parental education and attending physical education (PE) were positively associated with PA across multiple PA outcomes. Adolescent linguistic acculturation was inversely associated with participation in community sports, whereas parental linguistic acculturation was positively associated with PA at school. In girls, PA in school and community settings was inversely associated with TV viewing and positively associated with PE participation.
These findings highlight similarities and differences in correlates of PA among boys and girls, and point towards potential sources of opportunities as well as disparities for PA behaviors in Mexican-origin adolescents.
Mexican American; acculturation; physical education
While gliomas are the most common primary brain tumors, their etiology is largely unknown. To identify novel risk loci for glioma, we conducted genome-wide association (GWA) analysis of two case–control series from France and Germany (2269 cases and 2500 controls). Pooling these data with previously reported UK and US GWA studies provided data on 4147 glioma cases and 7435 controls genotyped for 424 460 common tagging single-nucleotide polymorphisms. Using these data, we demonstrate two statistically independent associations between glioma and rs11979158 and rs2252586, at 7p11.2 which encompasses the EGFR gene (population-corrected statistics, Pc = 7.72 × 10−8 and 2.09 × 10−8, respectively). Both associations were independent of tumor subtype, and were independent of EGFR amplification, p16INK4a deletion and IDH1 mutation status in tumors; compatible with driver effects of the variants on glioma development. These findings show that variation in 7p11.2 is a determinant of inherited glioma risk.
Mexican-American girls have one of the fastest rates of decline in age at menarche. To date, no study has addressed the role of psychosocial factors on age at menarche in this population. Using data from a longitudinal cohort of Mexican-American girls from the Houston, Texas, metropolitan area recruited in 2005, the authors investigated associations between family life and socioeconomic environment and age at menarche in 523 girls. After adjusting for maternal age at menarche, daughter's age, and body mass index at baseline, perception of family life environment as conflict-prone was significantly associated with an earlier age at menarche (< 11 years). Additionally, there was a 2-fold higher risk (odds ratio = 2.22, 95% confidence interval: 1.12, 4.40) of early menarche among daughters of mothers who were single parents compared with those who were not. Furthermore, girls who matured early had a 2.5-fold increased risk (odds ratio = 2.69, 95% confidence interval: 1.04, 6.96) of experimenting with cigarettes compared with those who had an average-to-late age at menarche (≥ 11 years). This study provides important information regarding the role of family life environment and single parenting on age at menarche in Mexican Americans. Awareness of the impact of the family life environment and fathers’ absence during the early years should be emphasized when addressing early age at menarche across cultures.
family cohesion; family conflict; menarche; Mexican Americans; single parenting; smoking; social support
Sensation seeking tendencies tend to manifest during adolescence and are associated with both health-compromising behaviors and health-enhancing behaviors. The purpose of this study is to evaluate the relationship between sensation seeking and physical activity, a health-enhancing behavior, and between sensation seeking and experimenting with cigarettes, a health compromising-behavior, among a cohort of Mexican origin adolescents residing in the United States with different levels of acculturation.
In 2009, 1,154 Mexican origin youth (50.5% girls, mean age 14.3 years (SD = 1.04)) provided data on smoking behavior, physical activity, linguistic acculturation, and sensation seeking. We conducted Pearson’s χ2 tests to examine the associations between categorical demographic characteristics (i.e. gender, age, country of birth and parental educational attainment) and both cigarette experimentation and physical activity and Student’s t-tests to examine mean differences on the continuous variables (i.e. sensation seeking subscale) by the behaviors. We examined mean differences in the demographic characteristics, acculturation, and both behaviors for each of the sensation seeking subscales using analysis of variance (ANOVA). To examine relationships between the sensation seeking subscales, gender, and both behaviors, at different levels of acculturation we completed unconditional logistic regression analyses stratified by level of acculturation.
Overall, 23.3% had experimented with cigarettes and 29.0% reported being physically active for at least 60 minutes/day on at least 5 days/week. Experimenting with cigarettes and being physically active were more prevalent among boys than girls. Among girls, higher levels of sensation seeking tendencies were associated with higher levels of acculturation and experimentation with cigarettes, but not with physical activity. Among boys, higher levels of sensation seeking tendencies were associated with higher levels of acculturation, experimenting with cigarettes and being physically active.
Our results suggest that interventions designed to prevent smoking among Mexican origin youth may need to address social aspects associated with acculturation, paying close attention to gendered manifestations of sensation seeking.
Smoking behavior; Physical activity; Acculturation; Sensation seeking; Gender; Mexican origin youth
Gliomas are tumors of glial origin formed in the central nervous system and exhibit profound morphological and genetic heterogeneity. The etiology of this heterogeneity involves an interaction between genetic alterations and environmental risk factors. Scientific evidence suggests that certain natural dietary components, such as phytoestrogens, flavonoids, polyunsaturated fatty acids and vitamins may exert a protective effect against gliomas by changing the nature of the interaction between genetics and environment. Similarly, certain anti-inflammatory drugs and dietary modifications, such as methionine restriction and the adoption of low-calorie or ketogenic diets, may take advantage of glioma and normal glial cells’ differential requirements for glucose, methionine, and ketone bodies and may therefore be effective as part of preventive or treatment strategies for gliomas. Treatment trials of glioma patients and chemoprevention trials of individuals with a known genetic predisposition to glioma using the most promising of these agents, such as the anti-inflammatory drugs curcumin and gamma-linolenic acid, are needed to validate or refute these agents’ putative role in gliomas.
glioma; glioblastoma; prevention; diet; vitamins
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.
anaplastic oligodendroglioma; epidemiology; mixed glioma; oligodendroglioma; risk factors
Overall, Latinas are more likely to be diagnosed with a more advanced stage of breast cancer, and are 20% more likely to die of breast cancer than non-Hispanic white women. It is estimated that from 2003–2006, $82.0 billion in direct medical care expenditures, in addition to 100,000 lives annually, could be saved by eliminating health disparities experienced by Latinos and increasing the use of up to five preventive services in the U.S. An additional 3,700 lives could be saved if 90% of women ≥40 years were recently screened for breast cancer. We examined risk for breast cancer in a case-control population-based sample of Mexican-origin women in Harris County, TX (n=714), where rates of breast cancer mortality for Latina women have doubled since 1990. Half of breast cancer cases (n=119) were diagnosed before the age of 50. In a multivariable model, women with a family history of breast cancer (OR=4.3), born in Mexico and having high levels of language acculturation (OR=2.5), and without health insurance (OR=1.6) were found to have the highest risk of breast cancer. Because Mexican-origin women were found to be of high-risk for early onset pre-menopausal breast cancer, we recommend policies targeting screening, education and treatment to prevent increased disparities in mortality. The inclusion of community members and policymakers as partners in these endeavors would further safeguard against an increase in cancer health disparities, and aid in formulating a policy agenda congruent with scientifically-based, community-driven policy efforts addressing breast cancer screening, education and treatment in this vulnerable population.