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Immune factors preceding diagnosis of glioma: a Prostate Lung Colorectal Ovarian Cancer Screening Trial nested case-control study.
BackgroundEpidemiological studies of adult glioma have identified genetic and environmental risk factors, but much remains unclear. The aim of the current study was to evaluate anthropometric, disease-related, and prediagnostic immune-related factors for relationship with glioma risk.MethodsWe conducted a nested case-control study among the intervention arm of the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) Screening Trial. One hundred and twenty-four glioma cases were identified and each matched to four controls. Baseline characteristics were collected at enrollment and were evaluated for association with glioma status. Serum specimens were collected at yearly intervals and were analyzed for immune-related factors including TGF-β1, TNF-α, total IgE, and allergen-specific IgE. Immune factors were evaluated at baseline in a multivariate conditional logistic regression model, along with one additional model that incorporated the latest available measurement.ResultsA family history of glioma among first-degree relatives was associated with increased glioma risk (OR = 4.41, P = .002). In multivariate modeling of immune factors at baseline, increased respiratory allergen-specific IgE was inversely associated with glioma risk (OR for allergen-specific IgE > 0.35 PAU/L: 0.59, P = .03). A logistic regression model that incorporated the latest available measurements found a similar association for allergen-specific IgE (P = .005) and showed that elevated TGF-β1 was associated with increased glioma risk (P-value for trend <.0001).ConclusionThe results from this prospective prediagnostic study suggest that several immune-related factors are associated with glioma risk. The association observed for TGF-β1 when sampling closer to the time of diagnosis may reflect the nascent brain tumor's feedback on immune function
Breast cancer incidence and mortality trends in an affluent population: Marin County, California, USA, 1990–1999
BACKGROUND: Elevated rates of breast cancer in affluent Marin County, California, were first reported in the early 1990s. These rates have since been related to higher regional prevalence of known breast cancer risk factors, including low parity, education, and income. Close surveillance of Marin County breast cancer trends has nevertheless continued, in part because distinctive breast cancer patterns in well-defined populations may inform understanding of breast cancer etiology. METHODS: Using the most recent incidence and mortality data available from the California Cancer Registry, we examined rates and trends for 1990–1999 for invasive breast cancer among non-Hispanic, white women in Marin County, in other San Francisco Bay Area counties, and in other urban California counties. Rates were age adjusted to the 2000 US standard, and temporal changes were evaluated with weighted linear regression. RESULTS: Marin County breast cancer incidence rates between 1990 and 1999 increased 3.6% per year (95% confidence interval, 1.8–5.5), six times more rapidly than in comparison areas. The increase was limited to women aged 45–64 years, in whom rates increased at 6.7% per year (95% confidence interval, 3.8–9.6). Mortality rates did not change significantly in Marin County despite 3–5% yearly declines elsewhere. CONCLUSION: Patterns of breast cancer incidence and mortality in Marin County are unlike those in other California counties, and they are probably explained by Marin County's unique sociodemographic characteristics. Similar trends may have occurred in other affluent populations for which available data do not permit annual monitoring of cancer occurrence
Daily intake of antioxidants in relation to survival among adult patients diagnosed with malignant glioma
<p>Abstract</p> <p>Background</p> <p>Malignant glioma is a rare cancer with poor survival. The influence of diet and antioxidant intake on glioma survival is not well understood. The current study examines the association between antioxidant intake and survival after glioma diagnosis.</p> <p>Methods</p> <p>Adult patients diagnosed with malignant glioma during 1991-1994 and 1997-2001 were enrolled in a population-based study. Diagnosis was confirmed by review of pathology specimens. A modified food-frequency questionnaire interview was completed by each glioma patient or a designated proxy. Intake of each food item was converted to grams consumed/day. From this nutrient database, 16 antioxidants, calcium, a total antioxidant index and 3 macronutrients were available for survival analysis. Cox regression estimated mortality hazard ratios associated with each nutrient and the antioxidant index adjusting for potential confounders. Nutrient values were categorized into tertiles. Models were stratified by histology (Grades II, III, and IV) and conducted for all (including proxy) subjects and for a subset of self-reported subjects.</p> <p>Results</p> <p>Geometric mean values for 11 fat-soluble and 6 water-soluble individual antioxidants, antioxidant index and 3 macronutrients were virtually the same when comparing all cases (n = 748) to self-reported cases only (n = 450). For patients diagnosed with Grade II and Grade III histology, moderate (915.8-2118.3 mcg) intake of fat-soluble lycopene was associated with poorer survival when compared to low intake (0.0-914.8 mcg), for self-reported cases only. High intake of vitamin E and moderate/high intake of secoisolariciresinol among Grade III patients indicated greater survival for all cases. In Grade IV patients, moderate/high intake of cryptoxanthin and high intake of secoisolariciresinol were associated with poorer survival among all cases. Among Grade II patients, moderate intake of water-soluble folate was associated with greater survival for all cases; high intake of vitamin C and genistein and the highest level of the antioxidant index were associated with poorer survival for all cases.</p> <p>Conclusions</p> <p>The associations observed in our study suggest that the influence of some antioxidants on survival following a diagnosis of malignant glioma are inconsistent and vary by histology group. Further research in a large sample of glioma patients is needed to confirm/refute our results.</p
Adult infiltrating gliomas with WHO 2016 integrated diagnosis: additional prognostic roles of ATRX and TERT
The “integrated diagnosis” for infiltrating gliomas in the 2016 revised World Health Organization (WHO) classification of tumors of the central nervous system requires assessment of the tumor for IDH mutations and 1p/19q codeletion. Since TERT promoter mutations and ATRX alterations have been shown to be associated with prognosis, we analyzed whether these tumor markers provide additional prognostic information within each of the five WHO 2016 categories. We used data for 1206 patients from the UCSF Adult Glioma Study, the Mayo Clinic and The Cancer Genome Atlas (TCGA) with infiltrative glioma, grades II-IV for whom tumor status for IDH, 1p/19q codeletion, ATRX, and TERT had been determined. All cases were assigned to one of 5 groups following the WHO 2016 diagnostic criteria based on their morphologic features, and IDH and 1p/19q codeletion status. These groups are: (1) Oligodendroglioma, IDH-mutant and 1p/19q-codeleted; (2) Astrocytoma, IDH-mutant; (3) Glioblastoma, IDH-mutant; (4) Glioblastoma, IDH-wildtype; and (5) Astrocytoma, IDH-wildtype. Within each group, we used univariate and multivariate Cox proportional hazards models to assess associations of overall survival with patient age at diagnosis, grade, and ATRX alteration status and/or TERT promoter mutation status. Among Group 1 IDH-mutant 1p/19q-codeleted oligodendrogliomas, the TERT-WT group had significantly worse overall survival than the TERT-MUT group (HR: 2.72, 95% CI 1.05–7.04, p = 0.04). In both Group 2, IDH-mutant astrocytomas and Group 3, IDH-mutant glioblastomas, neither TERT mutations nor ATRX alterations were significantly associated with survival. Among Group 4, IDH-wildtype glioblastomas, ATRX alterations were associated with favorable outcomes (HR: 0.36, 95% CI 0.17–0.81, p = 0.01). Among Group 5, IDH-wildtype astrocytomas, the TERT-WT group had significantly better overall survival than the TERT-MUT group (HR: 0.48, 95% CI 0.27–0.87), p = 0.02). Thus, we present evidence that in certain WHO 2016 diagnostic groups, testing for TERT promoter mutations or ATRX alterations may provide additional useful prognostic information
The association between antihypertensive drugs and glioma
We pursued an association between hypertension and gliomas by investigating whether antihypertensive drugs (AHD) are associated with an increased glioma risk by a population-based nested case–control study using the PHARMO database; this links dispensing records of prescription drugs to hospital discharge data on an individual basis. Pathological data were derived from the Dutch nationwide registry of histo- and cytopathology. A total of 306 glioma cases incident between 1997 and 2003 were matched to 1108 controls for year of birth, sex, geographical region and duration of follow-up. Exposure was defined as cumulative duration of AHD use and, in an alternative analysis, as cumulative dose. We estimated the magnitude of the association with conditional logistic regression analysis. Cumulative use of any AHD for more than 6 months was associated with an increased risk of glioma (OR 1.45; 95% CI 1.03–2.04). After stratification for different groups of AHD, no significantly increased risk of glioma was found for any class of AHD. After excluding a latency period of 3 years before the date of diagnosis, no association was found. In conclusion, the use of AHD seems to be associated with an increased risk of glioma, but this is probably not causal
The Fourth International Symposium on the Intraductal Approach to Breast Cancer, Santa Barbara, California, 10–13 March 2005
Intraductal approaches encompass procedures and technologies that are designed to access and interrogate the ductal–alveolar systems of the human breast, and include nipple aspiration, ductal lavage, random periareolar fine needle aspiration, and ductoscopy. These approaches are being used to collect and analyze fluids and cells to develop methods for breast cancer detection and risk assessment; to introduce imaging technologies to explore the mammary tree for abnormalities; to administer therapeutic and/or preventive agents directly to the breast tissue; and to explore the biology of the normal mammary gland. The latest research findings in these areas, presented at The 4th International Symposium on the Intraductal Approach to Breast Cancer in 2005, are summarized in this report
Recent changes in breast cancer incidence and risk factor prevalence in San Francisco Bay area and California women: 1988 to 2004
IntroductionHistorically, the incidence rate of breast cancer among non-Hispanic white women living in the San Francisco Bay area (SFBA) of California has been among the highest in the world. Substantial declines in breast cancer incidence rates have been documented in the United States and elsewhere during recent years. In light of these reports, we examined recent changes in breast cancer incidence and risk factor prevalence among non-Hispanic white women in the SFBA and other regions of California.MethodsAnnual age-adjusted breast cancer incidence and mortality rates (1988 to 2004) were obtained from the California Cancer Registry and analyzed using Joinpoint regression. Population-based risk factor prevalences were calculated using two data sources: control subjects from four case-control studies (1989 to 1999) and the 2001 and 2003 California Health Interview Surveys.ResultsIn the SFBA, incidence rates of invasive breast cancer increased 1.3% per year (95% confidence interval [CI], 0.7% to 2.0%) in 1988-1999 and decreased 3.6% per year (95% CI, 1.6% to 5.6%) in 1999-2004. In other regions of California, incidence rates of invasive breast cancer increased 0.8% per year (95% CI, 0.4% to 1.1%) in 1988-2001 and decreased 4.4% per year (95% CI, 1.4% to 7.3%) in 2001-2004. In both regions, recent (2000-2001 to 2003-2004) decreases in invasive breast cancer occurred only in women 40 years old or older and in women with all histologic subtypes and tumor sizes, hormone receptor-defined types, and all stages except distant disease. Mortality rates declined 2.2% per year (95% CI, 1.8% to 2.6%) from 1988 to 2004 in the SFBA and the rest of California. Use of estrogen-progestin hormone therapy decreased significantly from 2001 to 2003 in both regions. In 2003-2004, invasive breast cancer incidence remained higher (4.2%) in the SFBA than in the rest of California, consistent with the higher distributions of many established risk factors, including advanced education, nulliparity, late age at first birth, and alcohol consumption.ConclusionOngoing surveillance of breast cancer occurrence patterns in this high-risk population informs breast cancer etiology through comparison of trends with lower-risk populations and by highlighting the importance of examining how broad migration patterns influence the geographic distribution of risk factors
Impact of TGF-ß1 -509C/T and 869T/C polymorphisms on glioma risk and patient prognosis
Transforming growth factor beta (TGF-ß) plays an important role in carcinogenesis. Two polymorphisms in the TGF-ß1 gene (-509C/T and 869T/C) were described to influence susceptibility to gastric and breast cancers. The 869T/C polymorphism was also associated with overall survival in breast cancer patients. In the present study, we investigated the relevance of these TGF-ß1 polymorphism in glioma risk and prognosis. A case-control study that included 114 glioma patients and 138 cancer-free controls was performed. Single nucleotide polymorphisms (SNPs) were evaluated by polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP). Univariate and multivariate logistic regression analyses were used to calculate odds ratio (OR) and 95 % confidence intervals (95 % CI). The influence of TGF-ß1 -509C/T and 869T/C polymorphisms on glioma patient survival was evaluated by a Cox regression model adjusted for patients' age and sex and represented in Kaplan-Meier curves. Our results demonstrated that TGF-ß1 gene polymorphisms -509C/T and 869T/C are not significantly associated with glioma risk. Survival analyses showed that the homozygous -509TT genotype associates with longer overall survival of glioblastoma (GBM) patients when compared with patients carrying CC + CT genotypes (OR, 2.41; 95 % CI, 1.06-5.50; p = 0.036). In addition, the homozygous 869CC genotype is associated with increased overall survival of GBM patients when compared with 869TT + TC genotypes (OR, 2.62; 95 % CI, 1.11-6.17; p = 0.027). In conclusion, this study suggests that TGF-ß1 -509C/T and 869T/C polymorphisms are not significantly associated with risk for developing gliomas but may be relevant prognostic biomarkers in GBM patients.This work was supported by Fundação para a Ciência e Tecnologia, Portugal (PTDC/SAU-GMG/113795/2009
and SFRH/BPD/33612/2009 to B.M.C.; SFRH/BD/88121/2012 to J.V.C.; SFRH/BD/92786/2013 to C.S.G.;
PTDC/SAU-ONC/115513/2009 to R.R.)
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