Mitochondrial DNA sequence variation and risk of glioma.

BACKGROUND: Malignant gliomas are the most common primary adult brain tumors, with a poor prognosis and ill-defined etiology. Mitochondrial DNA (mtDNA) sequence variation has been linked with certain cancers; however, research on glioma is lacking. METHODS: We examined the association of common (minor allele frequency ≥ 5%) germline mtDNA variants and haplogroups with glioma risk in 1,566 glioma cases and 1,017 controls from a US case-control study, and 425 glioma cases and 1,534 matched controls from the UK Biobank cohort (UKB). DNA samples were genotyped using the UK Biobank array that included a set of common and rare mtDNA variants. Risk associations were examined separately for glioblastoma (GBM) and lower grade tumors (non-GBM). RESULTS: In the US study, haplogroup W was inversely associated with glioma when compared with haplogroup H (OR = 0.43, 95%CI: 0.23-0.79); this association was not demonstrated in the UKB (OR = 1.07, 95%CI: 0.47-2.43). In the UKB, the variant m.3010G > A was significantly associated with GBM (OR = 1.32; 95%CI: 1.01-1.73; p = 0.04), but not non-GBM (1.23; 95%CI: 0.78-1.95; p = 0.38); no similar association was observed in the US study. In the US study, the variant m.14798 T > C, was significantly associated with non-GBM (OR = 0.72; 95%CI: 0.53-0.99), but not GBM (OR = 0.86; 95%CI: 0.66-1.11), whereas in the UKB, a positive association was observed between this variant and GBM (OR = 1.46; 95%CI: 1.06-2.02) but not non-GBM (OR = 0.92; 95%CI: 0.52-1.63). None of these associations were significant after adjustment for multiple testing. CONCLUSION: The association of inherited mtDNA variation, including rare and singleton variants, with glioma risk merits further study.

A prospective study of pre-diagnostic circulating tryptophan and kynurenine, and the kynurenine/tryptophan ratio and risk of glioma.

BACKGROUND: Conversion of tryptophan to kynurenine may promote glioma growth and suppress antitumor immune response through activation of the aryl hydrocarbon receptor. Expression of the enzymes indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase-2 in the glioma microenvironment has been shown to mediate tryptophan catabolism, and the ratio between kynurenine and tryptophan is considered an indirect measure of this enzyme activity. METHODS: We explored whether tryptophan, kynurenine, and the ratio of kynurenine to tryptophan (KTR) in pre-diagnostic blood samples was related to risk of glioma in a nested case-control study of 84 cases and 168 matched controls from two cohort studies - the Nurses' Health Study, and the Health Professionals Follow-Up Study. Tryptophan and kynurenine were measured by liquid chromatography-tandem mass spectrometry. Conditional logistic regression models were used to estimate risk ratios (RRs) and 95% confidence intervals (95%CI) for the associations between tertiles of these analytes and glioma risk. RESULTS: We observed no significant associations for either analyte or the ratio for risk of glioma overall. The RR for the highest KTR tertile compared to the lowest for all gliomas was 0.74 (95% CI: 0.34-1.59). All results were essentially unchanged in lagged analyses excluding the first two or four years of follow up, though data were sparse. CONCLUSION: Our findings do not provide support for an association between pre-diagnostic circulating KTR and risk of glioma.

Mitochondrial DNA sequence variation and risk of meningioma.

BACKGROUND: Risk factors for meningioma include female gender, African American race, high body mass index (BMI), and exposure to ionizing radiation. Although genome-wide association studies (GWAS) have identified two nuclear genome risk loci for meningioma (rs12770228 and rs2686876), the relation between mitochondrial DNA (mtDNA) sequence variants and meningioma is unknown. METHODS: We examined the association of 42 common germline mtDNA variants (minor allele frequency ≥ 5%), haplogroups, and genes with meningioma in 1080 controls and 478 meningioma cases from a case-control study conducted at medical centers in the southeastern United States. Associations were examined separately for meningioma overall and by WHO grade (n = 409 grade I and n = 69 grade II/III). RESULTS: Overall, meningioma was significantly associated with being female (OR 2.85; 95% CI 2.21-3.69), self-reported African American race (OR 2.38, 95% CI 1.41-3.99), and being overweight (OR 1.48; 95% CI 1.11-1.97) or obese (OR 1.70; 95% CI 1.25-2.31). The variant m.16362T > C (rs62581341) in the mitochondrial control region was positively associated with grade II/III meningiomas (OR 2.33; 95% CI 1.14-4.77), but not grade I tumors (OR 0.99; 95% CI 0.64-1.53). Haplogroup L, a marker for African ancestry, was associated with meningioma overall (OR 2.92; 95% CI 1.01-8.44). However, after stratifying by self-reported race, this association was only apparent among the few self-reported Caucasians with this haplogroup (OR 6.35; 95% CI 1.56-25.9). No other mtDNA variant, haplogroup, or gene was associated with meningioma. CONCLUSION: Common mtDNA variants and major mtDNA haplogroups do not appear to have associations with the odds of developing meningioma.

A prospective study of inflammatory biomarkers and growth factors and risk of glioma in the UK Biobank.

PURPOSE: The role of growth factors and inflammation in the onset of glioma is poorly understood, and conflicting reports of associations of circulating IGF-1 and inflammatory biomarkers with glioma risk exist in the literature. We examined associations between C-reactive protein (CRP), white blood cell count (WBC), neutrophil-to-lymphocyte ratio (NLR), and insulin-like growth factor-1 (IGF-1) and glioma risk in the UK Biobank cohort. METHODS: Hazard ratios (HR) and 95% confidence intervals (CI) for glioma according to circulating biomarkers concentrations were calculated using Cox proportional hazards regression, adjusted for age, sex, race, and education. Analyses were conducted separately for glioma overall and by glioma subtype. RESULTS: We identified 417 incident glioma cases among 428,537 participants with 3,255,815 person-years of follow up. Weak, non-significant associations were observed with increasing levels of these biomarkers for risk of glioma overall or by glioma subtype. Among women only, IGF-1 in the highest quartile was positively associated with glioma risk compared to the lowest quartile (HR=1.64, 95%CI: 1.03-2.60, p-trend=0.08), as was NLR (HR=1.54, 95%CI: 1.00-2.39, p-trend=0.05). CONCLUSION: In this prospective cohort, we found no significant associations between the inflammatory biomarkers CRP and WBC and the development of glioma. NLR and IGF-1 were associated with risk in women, but not men. When considered with previous studies, further investigation of NLR and IGF-1 as markers of glioma risk appears warranted, particularly in women.

Alcohol intake and risk of glioma: results from three prospective cohort studies.

PURPOSE: The association between alcohol intake and glioma remains unclear. We evaluated the association between alcohol intake and incidence of glioma in three large, prospective cohort studies with repeated alcohol assessments. METHODS: We harnessed data from three studies with repeat alcohol assessment to compute hazard ratios (HR) and 95% confidence intervals (CI) for glioma by overall alcohol intake and intake from specific beverages using Cox proportional hazards regression, adjusted for age, cohort, body mass index, smoking status, and caloric intake. Analyses were conducted separately for glioma overall and for glioblastoma (GBM). RESULTS: We confirmed 554 incident glioma cases (362 GBM) among 237,505 participants with 6,216,378 person-years of follow up. Cumulative average alcohol intake was associated with reduced risk of glioma (HR = 0.75, 95%CI:0.56-0.99 comparing > 8-15 to ≤ 0.5 g/d; HR = 0.71, 95%CI:0.53-0.96 comparing > 15 g/d to ≤ 0.5 g/d). When stratified by sex, for the same comparisons, the HRs for men were 0.57 (95%CI:0.36-0.89) and 0.79 (0.53-1.16), and for women 0.90 (95%CI:0.62-1.30) and 0.62, 95%CI:0.39-0.97. Results were consistent when examining cumulative average, baseline, and recent intake, and with a 4 year lag. CONCLUSION: These results provide evidence against a positive association between alcohol intake and glioma risk. Alcohol intake was associated with reduced risk of glioma in both men and women.

Prospective study of sleep duration and glioma risk.

PURPOSE: Both long and short sleep duration have been linked with risk of some cancers, but evidence for glioma is lacking. METHODS: Using prospective data from the UK Biobank (UKB), the Nurses' Health Study (NHS), and the Health Professionals Follow-Up Study (HPFS), we examined the association between self-reported hours of sleep and incident glioma in multivariable-adjusted Cox proportional hazards models. RESULTS: In the UKB, compared to 7 h, sleep durations of < 7 h (HR = 0.90; 95% CI 0.70-1.16) or > 7 h (HR = 1.05; 95% CI 0.85-1.30) were not significantly associated with glioma risk. Likewise, no significant associations were found between sleep duration and glioma risk in the NHS/HPFS for either < 7 h (HR = 0.93; 95% CI 0.69-1.26) or > 7 h (HR = 1.22; 95% CI 0.94-1.57), compared to 7 h. Results were similar for low-grade and high-grade glioma, did not materially change after lagging 2 years, or after accounting for factors known to disrupt sleep. CONCLUSION: Sleep duration was not associated with incident glioma in either the UKB or the NHS/HPFS cohorts.

Prevalence of Self-Reported Hypertension and Antihypertensive Medication Use by County and Rural-Urban Classification - United States, 2017.

In 2017, approximately one in three U.S. adults reported having been told by a health care professional that they had high blood pressure (hypertension) (1). Although hypertension prevalence is well documented at national and state levels, less is known about rural-urban variation and county-level prevalence. To examine prevalence of self-reported hypertension and antihypertensive medication use by rural-urban classification and county, CDC analyzed data reported by 442,641 adults aged ≥18 years who participated in the 2017 Behavioral Risk Factor Surveillance System (BRFSS). In rural (noncore) areas, 40.0% (unadjusted prevalence) of adults reported having hypertension, whereas in the most urban (large central metro) areas, 29.4% reported having hypertension. Age-standardized hypertension prevalence was significantly higher in the most rural areas, compared with the most urban areas within nearly all categories of age, sex, and other demographic characteristics. Model-based hypertension prevalence across counties ranged from 18.0% to 55.0% and was highest in Southeastern* and Appalachian† counties. Model-based county-level prevalence of antihypertensive medication use among adults with hypertension ranged from 54.3% to 84.7%. Medication use also was higher in rural areas compared with use in most urban areas, with prevalence highest in Southeastern and Appalachian counties as well as counties in the Dakotas and Nebraska. CDC is working with states to enhance hypertension awareness and management through a strategy of team-based care that involves physicians, nurses, pharmacists, dietitians, and community health workers. The increased use of telemedicine to support this strategy might improve access to care among underserved populations.

Prevalence of Self-Reported Hypertension and Antihypertensive Medication Use Among Adults - United States, 2017.

Hypertension, or high blood pressure, is a major risk factor for heart disease and stroke (1). The prevalence of hypertension is higher among men than among women, increases with age, is highest among non-Hispanic blacks (blacks) (2), and has been consistently highest in the Southeastern region of the United States (1). To update prevalence estimates for self-reported hypertension and use of antihypertensive medication, CDC analyzed data from the 2017 Behavioral Risk Factor Surveillance System (BRFSS). The overall (unadjusted) prevalence of self-reported hypertension was 32.4% (95% confidence interval [CI] = 32.1%-32.7%). The age-standardized, median state-specific prevalence of self-reported hypertension was 29.7% (range = 24.3%-38.6%). Overall age-standardized hypertension prevalence was higher among men (32.9%) than among women (27.0%), highest among blacks (40.0%), decreased with increasing levels of education and household income, and was generally highest in the Southeastern and Appalachian states.* Among persons reporting hypertension, the overall unadjusted prevalence of self-reported antihypertensive medication use was 76.0% (95% CI = 75.5%-76.4%). The age-standardized, median state-specific prevalence of antihypertensive medication use among persons with reported hypertension was 59.4% (range = 50.2%-71.2%). Prevalence was higher among women than men, highest among blacks compared with other racial/ethnic groups, and highest among states in the Southeast, Appalachia, and the Dakotas. These findings can help inform CDC's initiatives to enhance hypertension awareness, treatment, and control across all states.

The Diesel Exhaust in Miners study: a nested case-control study of lung cancer and diesel exhaust.

BACKGROUND: Most studies of the association between diesel exhaust exposure and lung cancer suggest a modest, but consistent, increased risk. However, to our knowledge, no study to date has had quantitative data on historical diesel exposure coupled with adequate sample size to evaluate the exposure-response relationship between diesel exhaust and lung cancer. Our purpose was to evaluate the relationship between quantitative estimates of exposure to diesel exhaust and lung cancer mortality after adjustment for smoking and other potential confounders. METHODS: We conducted a nested case-control study in a cohort of 12 315 workers in eight non-metal mining facilities, which included 198 lung cancer deaths and 562 incidence density-sampled control subjects. For each case subject, we selected up to four control subjects, individually matched on mining facility, sex, race/ethnicity, and birth year (within 5 years), from all workers who were alive before the day the case subject died. We estimated diesel exhaust exposure, represented by respirable elemental carbon (REC), by job and year, for each subject, based on an extensive retrospective exposure assessment at each mining facility. We conducted both categorical and continuous regression analyses adjusted for cigarette smoking and other potential confounding variables (eg, history of employment in high-risk occupations for lung cancer and a history of respiratory disease) to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Analyses were both unlagged and lagged to exclude recent exposure such as that occurring in the 15 years directly before the date of death (case subjects)/reference date (control subjects). All statistical tests were two-sided. RESULTS: We observed statistically significant increasing trends in lung cancer risk with increasing cumulative REC and average REC intensity. Cumulative REC, lagged 15 years, yielded a statistically significant positive gradient in lung cancer risk overall (P (trend) = .001); among heavily exposed workers (ie, above the median of the top quartile [REC ≥ 1005 µg/m(3)-y]), risk was approximately three times greater (OR = 3.20, 95% CI = 1.33 to 7.69) than that among workers in the lowest quartile of exposure. Among never smokers, odd ratios were 1.0, 1.47 (95% CI = 0.29 to 7.50), and 7.30 (95% CI = 1.46 to 36.57) for workers with 15-year lagged cumulative REC tertiles of less than 8, 8 to less than 304, and 304 µg/m(3)-y or more, respectively. We also observed an interaction between smoking and 15-year lagged cumulative REC (P (interaction) = .086) such that the effect of each of these exposures was attenuated in the presence of high levels of the other. CONCLUSION: Our findings provide further evidence that diesel exhaust exposure may cause lung cancer in humans and may represent a potential public health burden.

Occupational exposure to pesticides and risk of adult brain tumors.

The authors examined incident glioma and meningioma risk associated with occupational exposure to insecticides and herbicides in a hospital-based, case-control study of brain cancer. Cases were 462 glioma and 195 meningioma patients diagnosed between 1994 and 1998 in three US hospitals. Controls were 765 patients admitted to the same hospitals for nonmalignant conditions. Occupational histories were collected during personal interviews. Exposure to pesticides was estimated by use of a questionnaire, combined with pesticide measurement data abstracted from published sources. Using logistic regression models, the authors found no association between insecticide and herbicide exposures and risk for glioma and meningioma. There was no association between glioma and exposure to insecticides or herbicides, in men or women. Women who reported ever using herbicides had a significantly increased risk for meningioma compared with women who never used herbicides (odds ratio = 2.4, 95% confidence interval: 1.4, 4.3), and there were significant trends of increasing risk with increasing years of herbicide exposure (p = 0.01) and increasing cumulative exposure (p = 0.01). There was no association between meningioma and herbicide or insecticide exposure among men. These findings highlight the need to go beyond job title to elucidate potential carcinogenic exposures within different occupations.