Zhou, Renke

AbstractBackgroundFatigue is a consistently reported, severe symptom among patients with gliomas throughout the disease trajectory. Genomic pathways associated with fatigue in glioma patients have yet to be identified.MethodsClinical factors (performance status, tumor details, age, gender) were collected by chart review on glioma patients with fatigue (“I have lack of energy” on Functional Assessment of Cancer Therapy-Brain), as well as available genotyping data. Candidate genes in clock and inflammatory pathways were identified from a literature review, of which 50 single nucleotide polymorphisms (SNPs) in 7 genes were available. Clinical factors and SNPs identified by univariate analyses were included in a multivariate model for moderate-severe fatigue.ResultsThe study included 176 patients (median age = 47 years, 67% males). Moderate-severe fatigue was reported by 43%. Results from multivariate analysis revealed poor performance status and 2 SNPs were associated with fatigue severity. Moderate-severe fatigue was more common in patients with poor performance status (OR = 3.52, P < .01). For each additional copy of the minor allele in rs934945 (PER2) the odds of fatigue decreased (OR = 0.51, P < .05). For each additional copy of the minor allele in rs922270 (ARTNL2) the odds of fatigue increased (OR = 2.38, P < .01). Both of these genes are important in the circadian clock pathway, which has been implicated in diurnal preference, and duration and quality of sleep. No genes in the inflammatory pathway were associated with fatigue in the current study.ConclusionsIdentifying patients at highest risk for fatigue during treatment allows for improved clinical monitoring and enrichment of patient selection for clinical trials.

Abstract Background: Numerous epidemiologic studies have examined the association between aspirin (ASA), non-steroid anti-inflammatory drugs (NSAIDs) and the development of glioma, but the results have been inconsistent. The goal of this study was to evaluate the relationship between the intake of these drugs and glioma risk in a large, international case-control study. Methods: Between 2010 and 2015, the Glioma International Case-Control Study (GICC) recruited newly diagnosed glioma cases and matched controls in 14 different sites across five countries. Each subject was interviewed using a standardized questionnaire to obtain NSAIDs and ASA use. We examined the associations between ever use (at least &gt; 6 months), duration of drug use and glioma histology. Ever use data on 4533 glioma cases and 4171 controls was combined using maximum likelihood estimation/restricted maximum likelihood meta-analysis methods. Furthermore, based on a priori hypotheses, we performed subgroup analyses based on gender and glioma histological grades. Results: Use of ASA for &gt; 6 months was associated with a 33% lower glioma risk compared to those who never took it (adjusted Meta-OR 0.67, 95% CI 0.54-0.83). Duration of intake showed a significant trend test (p &lt; 0.0001), with ORs became lower for increasing number of years of ASA use. In subgroup analyses, intake of ASA was significantly associated with glioma risk in both men and women (adjusted Meta-OR = 0.65, 95% CI 0.51-0.84 for men; adjusted Meta-OR = 0.74, 95% CI 0.58-0.93 for women). ASA intake was protective for grade IV glioma (glioblastoma) and grade II/III glioma (adjusted meta-OR 0.63, 95% CI 0.5-0.8 for glioblastoma; adjusted meta-OR 0.67, 95% CI 0.50 - 0.89 for grade II/III glioma). For NSAIDs intake, ever use &gt; 6 months was not associated with glioma risk (adjusted meta-OR 0.87, 95% CI 0.71-1.07). However, NSAIDs use was protective for women (adjusted meta-OR 0.72, 95% CI 0.55-0.93) in subgroup analyses but not for men (adjusted meta-OR 1.03; 95% CI 0.86-1.23). The interaction between gender, NSAIDs and glioma risk was significant (p-value 0.0076).. Sensitivity analyses excluding those who took ASA or NSAIDs within the past 12 months for headache, and the removal of proxy respondents did not change our results. Conclusion: ASA was associated with a significant protective effect for glioma, but NSAIDs were only associated with reduced glioma risk in women. Given the possibility of recall bias in case-control studies of brain tumors, we may verify dosage and duration of drug intake in those countries with electronic pharmacy records within the GICC. Citation Format: Rose K. Lai, Renke Zhou, E. Susan Amirian, Christoffer Johansen, Michael E. Scheurer, Georgina N. Armstrong, Ching C. Lau, Elizabeth B. Claus, Jill S. Barnholtz-Sloan, Dora Il’yasova, Joellen Schildkraut, Francis Ali-Osman, Siegal Sadetzki, Richard Houlston, Robert B. Jenkins, Daniel Lachance, Sara H. Olson, Jonine L. Bernstein, Ryan T. Merrell, Margaret R. Wrensch, Faith G. Davis, Sanjay Shete, Christopher I. Amos, Beatrice S. Melin, Melissa Bondy. Aspirin, non-steroidal anti-inflammatory drugs (NSAIDs) and the risk of glioma: Results from the Glioma International Case Control Study. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3446.

AbstractVaricella zoster virus (VZV) is a neurotropic α‐herpesvirus that causes chickenpox and establishes life‐long latency in the cranial nerve and dorsal root ganglia of the host. To date, VZV is the only virus consistently reported to have an inverse association with glioma. The Glioma International Case‐Control Study (GICC) is a large, multisite consortium with data on 4533 cases and 4171 controls collected across five countries. Here, we utilized the GICC data to confirm the previously reported associations between history of chickenpox and glioma risk in one of the largest studies to date on this topic. Using two‐stage random‐effects restricted maximum likelihood modeling, we found that a positive history of chickenpox was associated with a 21% lower glioma risk, adjusting for age and sex (95% confidence intervals (CI): 0.65–0.96). Furthermore, the protective effect of chickenpox was stronger for high‐grade gliomas. Our study provides additional evidence that the observed protective effect of chickenpox against glioma is unlikely to be coincidental. Future studies, including meta‐analyses of the literature and investigations of the potential biological mechanism, are warranted.

Abstract Background: Several previous studies have found inverse associations between glioma susceptibility and a history of allergies or other atopic conditions. Some evidence indicates that respiratory allergies are likely to be particularly relevant with regard to glioma risk. Using data from the Glioma International Case-Control Study (GICC), we examined the effects of respiratory allergies and other atopic conditions on glioma risk. Methods: The GICC contains detailed information on history of atopic conditions for 4,533 cases and 4,171 controls, recruited from 14 study sites across five countries. Using two-stage random-effects restricted maximum likelihood modeling to calculate meta-analysis ORs, we examined the associations between glioma and allergy status, respiratory allergy status, asthma, and eczema. Results: Having a history of respiratory allergies was associated with an approximately 30% lower glioma risk, compared with not having respiratory allergies (mOR, 0.72; 95% confidence interval, 0.58–0.90). This association was similar when restricting to high-grade glioma cases. Asthma and eczema were also significantly protective against glioma. Conclusion: A substantial amount of data on the inverse association between atopic conditions and glioma has accumulated, and findings from the GICC study further strengthen the existing evidence that the relationship between atopy and glioma is unlikely to be coincidental. Impact: As the literature approaches a consensus on the impact of allergies in glioma risk, future research can begin to shift focus to what the underlying biologic mechanism behind this association may be, which could, in turn, yield new opportunities for immunotherapy or cancer prevention. Cancer Epidemiol Biomarkers Prev; 25(2); 282–90. ©2016 AACR.