E. Susan Amirian

Effects of antihistamine and anti-inflammatory medication use on risk of specific glioma histologies.

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; whereas 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 nonsteroidal anti‐inflammatory drugs, may contribute to the development of certain types of brain tumors.

Predictors of Survival among Pediatric and Adult Ependymoma Cases: A Study Using Surveillance, Epidemiology, and End Results Data from 1973 to 2007

Background: Despite previous research, prognostic factors for ependymoma remain relatively controversial. The purpose of our study was to examine demographic, clinical, and tumor attributes as potential predictors of survival using Surveillance, Epidemiology, and End Results (SEER) program data (1973–2007). Methods: All ependymoma (ICD-O-3 code 9391) and anaplastic ependymoma cases (ICD-O-3 code 9392) with complete data (n = 2,369 and n = 319, respectively) were included from SEER. Predictive Cox regression models were built separately among pediatric and adult cases. Recursive partitioning was used to corroborate results from regression models. Results: Among pediatric cases, tumor characteristics with a significantly increased mortality risk were anaplastic histology (vs. low grade, HR: 1.51, 95% CI: 1.04–2.19) and infratentorial tumor location (vs. spinal cord, HR: 3.86, 95% CI: 1.17–12.77). Among adults, supratentorial tumors were associated with higher mortality hazard (vs. spinal cord tumors) than infratentorial tumors (HR: 4.83, 95% CI: 3.49–6.68 and HR: 2.41, 95% CI: 1.79–3.25, respectively). Complete surgical resection of the tumor conferred the most protection among pediatric and adult patients. Conclusion: Our results indicate that treatment type and tumor characteristics are important prognostic factors in patients with ependymoma. However, there may be key differences between pediatric and adult cases regarding how these factors influence survival.

Potential role of gastrointestinal microbiota composition in prostate cancer risk

BackgroundAmong men in the U.S., prostate cancer is the most common cancer and the second leading cause of cancer death. Despite its prevalence, there are few established risk factors for prostate cancer. Some studies have found that intake of certain foods/nutrients may be associated with prostate cancer risk, but few have accounted for how intake and metabolic factors may interact to influence bioavailable nutrient levels and subsequent disease risk.Presentation of the hypothesisThe composition of the gastrointestinal (GI) microbiome may influence metabolism of dietary compounds and nutrients (e.g., plant phenols, calcium, choline) that may be relevant to prostate cancer risk. We, therefore, propose the hypothesis that GI microbiota may have a markedly different composition among individuals with higher prostate cancer risk. These individuals could have microbial profiles that are conducive to intestinal inflammation and/or are less favorable for the metabolism and uptake of chemopreventive agents.Testing the hypothesisBecause very little preliminary data exist on this potential association, a case–control study may provide valuable information on this topic. Such a study could evaluate whether the GI microbial profile is markedly different between three groups of individuals: healthy men, those with latent prostate cancer, and those with invasive prostate cancer. Any findings could then be validated in a larger study, designed to collect a series of specimens over time.Implications of the hypothesisGiven the plethora of information emerging from the Human Microbiome Project, this is an opportune time to explore associations between the microbiome and complex human diseases. Identification of profiles that alter the host’s risk for disease may clarify inconsistencies in the literature on dietary factors and cancer risk, and could provide valuable targets for novel cancer prevention strategies.

Approaching a Scientific Consensus on the Association between Allergies and Glioma Risk: A Report from the Glioma International Case-Control Study

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.

Pediatric and adult malignant peripheral nerve sheath tumors: an analysis of data from the surveillance, epidemiology, and end results program

Malignant peripheral nerve sheath tumors (MPNSTs) are rare soft tissue sarcomas that arise predominantly from Schwann cells. Despite the fact that MPNSTs have high local recurrence rates and are generally associated with poor prognosis, little is known about prognostic factors or effective clinical management for this tumor type. The purpose of this study was to describe the distributions of patient and tumor characteristics and to identify predictors of cause-specific survival among MPNST cases reported to SEER between 1973 and 2008. Patient and tumor characteristics were compared between pediatric and adult MPNST cases. Cox regression and tree-based survival analysis were used to examine factors associated with MPNST-related mortality separately among adults and children. A total of 1,315 MPNST cases were isolated from the 1973–2008 SEER dataset. Among pediatric cases, sex, race, and radiation therapy predicted MPNST survival, whereas among adults, tumor site, tumor grade, number of primary tumors, and tumor size were significant predictors. As tumor size at diagnosis/resection may be the only somewhat “modifiable” prognostic factor, future studies should aim to identify biological and social attributes associated with tumor size at diagnosis, separately among individuals with and without NF-1, in order to help identify earlier opportunities for clinical intervention.

Associations between arachidonic acid metabolism gene polymorphisms and prostate cancer risk.

The arachidonic acid (AA) pathway is suspected to be involved in the development of various cancers, including prostate cancer. However, the role of single nucleotide polymorphisms (SNPs) of AA pathway genes remains unclear. The purpose of this case–control study was to evaluate the association between prostate cancer risk and 14 such SNPs in the PTGS2, PTGES2, ALOX5, ALOX5AP, and LTA4H genes.

Anal cancer incidence and survival: comparing the greater San-Francisco bay area to other SEER cancer registries.

The incidence of squamous cell carcinoma of the anus, anal canal, and anorectum (SCCA) has increased over time. However, there are still no national guidelines on screening for SCCA among high-risk populations. Providers at University of California, San Francisco have been at the forefront of providing anal dysplasia screening. To determine whether such a screening program allows for earlier detection of abnormalities and consequently, improves patient survival, we conducted an ecological study using data from the Surveillance, Epidemiology, and End Results (SEER) program to compare the San Francisco-Oakland catchment area (SF-O) to other SEER sites where routine screening has not been as accessible. Cox regression models were utilized to assess the impact of residing in the SF-O region, versus other SEER sites, on cause-specific mortality hazard. Logistic regression was used to determine if site was associated with the probability of having an in situ versus invasive tumor among SCCA cases. All analyses were stratified on calendar time (1985–1995 and 1996–2008) to compare differences pre- and post- highly active anti-retroviral therapy. Among SCCA cases, being reported by the SF-O registry was associated with a four fold higher probability of having an in situ tumor (rather than an invasive tumor) [95% CI: 3.48–4.61], compared to sites outside of California, between 1996 and 2008. Cases reported from the SF-O region between 1996 and 2008 had a 39% lower mortality risk than those reported from registries outside California (95% CI: 0.51–0.72). However, there was no decrease in the rate of invasive SCCA over this period. This is the first ecological study to evaluate whether access to anal cancer screening programs may help improve patient survival by allowing for earlier detection of lesions. Our results imply that routine screening programs may help detect SCCA at an earlier stage and thus, potentially impact patient survival.

The Glioma International Case-Control Study: A Report From the Genetic Epidemiology of Glioma International Consortium

Decades of research have established only a few etiological factors for glioma, which is a rare and highly fatal brain cancer. Common methodological challenges among glioma studies include small sample sizes, heterogeneity of tumor subtypes, and retrospective exposure assessment. Here, we briefly describe the Glioma International Case-Control (GICC) Study (recruitment, 2010-2013), a study being conducted by the Genetic Epidemiology of Glioma International Consortium that integrates data from multiple data collection sites, uses a common protocol and questionnaire, and includes biospecimen collection. To our knowledge, the GICC Study is the largest glioma study to date that includes collection of blood samples, which will allow for genetic analysis and interrogation of gene-environment interactions.

Antihistamine use and immunoglobulin E levels in glioma risk and prognosis

OBJECTIVE An inverse association between personal history of allergies/asthma and glioma risk has been fairly consistently reported in the epidemiologic literature. However, the role of regular antihistamine use remains controversial due to a small number of studies reporting contradictory findings. We evaluated the association between regular use of oral antihistamines and glioma risk, adjusting for a number of relevant factors (e.g., immunoglobulin E levels and history of chickenpox). METHODS We used a subset of the Harris County Case-Control Study, which included 362 pathologically confirmed glioma cases and 462 cancer-free controls, to evaluate this association using unconditional multivariable logistic regression. These models were run among the overall study population and stratified by allergy status. Cox regression was utilized to examine whether antihistamine use was associated with mortality among all cases and separately among high-grade cases. RESULTS Antihistamine use was strongly associated with glioma risk among those with a positive allergy/asthma history (OR: 4.19, 95% CI: 2.06-8.51), but not among those with a negative history (OR: 1.59, 95% CI: 0.95-2.67). There were no significant associations between antihistamine use and survival among cases. CONCLUSION The current study implies that regular antihistamine use may increase glioma risk. However, several larger studies are necessary before definitive conclusions can be drawn.

Targeted Sequencing in Chromosome 17q Linkage Region Identifies Familial Glioma Candidates in the Gliogene Consortium

Glioma is a rare, but highly fatal, cancer that accounts for the majority of malignant primary brain tumors. Inherited predisposition to glioma has been consistently observed within non-syndromic families. Our previous studies, which involved non-parametric and parametric linkage analyses, both yielded significant linkage peaks on chromosome 17q. Here, we use data from next generation and Sanger sequencing to identify familial glioma candidate genes and variants on chromosome 17q for further investigation. We applied a filtering schema to narrow the original list of 4830 annotated variants down to 21 very rare (<0.1% frequency), non-synonymous variants. Our findings implicate the MYO19 and KIF18B genes and rare variants in SPAG9 and RUNDC1 as candidates worthy of further investigation. Burden testing and functional studies are planned.