The Incidence and Prevalence of Primary Central Nervous System (CNS) Tumours in Canada (2010-2017), and the Survival of Patients Diagnosed with CNS Tumours (2008-2017).

Primary central nervous system (CNS) tumours are heterogeneous, with different treatment pathways and prognoses depending on their histological and molecular classification. Due to their anatomical location, all CNS tumours, regardless of malignancy, can be debilitating. We used vital statistics linked to Canadian Cancer Registry data to estimate the age-standardized incidence rates (ASIR), Kaplan-Meier survival rates (SR), and limited-duration prevalence proportions (PP) of 25 histology-specific CNS tumour groups that were classified based on site and histology. During 2010-2017, 45,115 patients were diagnosed with 47,085 primary CNS tumours, of which 19.0% were unclassified. The average annual ASIR was 21.48/100,000 person-years and did not vary by sex. The ASIR increased with age, particularly for meningioma, unclassified tumours, and glioblastoma. The eight-year PP was 102.1/100,000 persons (index date 1 January 2018). The most common histology was meningioma (ASIR: 5.19; PP: 31.6). The overall five-year SR among 51,310 patients diagnosed during 2008-2017 was 57.2% (95% CI: 56.8-57.7%). SRs varied by tumour behaviour, histology, and patient age, with the lowest SR among glioblastoma patients (5-year SRs ranged from 1.3-25.7%). For non-malignant tumours, the 5-year SRs ranged from 37.4-100%. We provide the most up-to-date histology-specific surveillance estimates for primary CNS tumours in Canada.

Incidence and survival of primary central nervous system tumors diagnosed in 4 Canadian provinces from 2010 to 2015.

Background: The Brain Tumor Registry of Canada was established in 2016 to enhance infrastructure for surveillance and clinical research on Central Nervous System (CNS) tumors. We present information on primary CNS tumors diagnosed among residents of Canada from 2010 to 2015. Methods: Data from 4 provincial cancer registries were analyzed representing approximately 67% of the Canadian population. Age-standardized incidence rates (ASIR) and 95% confidence intervals (CI) were calculated using the 2011 Canadian population age distribution. Net survival was estimated using the Pohar-Perme method. Results: A total of 31 644 primary tumors were identified for an ASIR of 22.8 per 100 000 person-years. Nonmalignant tumors made up 47.1% of all classified tumors, with mixed behaviors present in over half of histology groupings. Unclassified were 19.5% of all tumors. The most common histological subtypes are meningiomas (ASIR = 5.5 per 100 000 person-years); followed by glioblastomas (ASIR 4.0 per 100 000 person-years). The overall 5-year net survival rate for CNS tumors was 65.5%; females 70.2% and males 60.4%. GBMs continue to be the most lethal CNS tumors for all sex and age groups. Conclusions: The low annual frequency of most CNS tumor subtypes emphasizes the value of population-based data on all primary CNS tumors diagnosed among Canadians. The large number of histological categories including mixed behaviors and the proportion of unclassified tumors emphasizes the need for complete reporting. Variation in incidence and survival across histological groups by sex and age highlights the need for comprehensive and histology-specific reporting. These data can be used to better inform research and health system planning.

Brain Metastases among Cancer Patients Diagnosed from 2010-2017 in Canada: Incidence Proportion at Diagnosis and Estimated Lifetime Incidence.

The incidence of BM among Canadian cancer patients is unknown. We aimed to estimate IP of BM at the time of cancer diagnosis and during the lifetime of patients with selected primary cancers. Data on BM at diagnosis from 2010-2017 was obtained from the CCR. Site-specific IPs of BM were estimated from provincial registries containing ≥90% complete data on BM. The CCR IP estimates and the IP estimates from literature were applied to the total diagnosed primary cancers to estimate the number of concurrent BM and lifetime BM from 2010-2017 in Canada, respectively. The annual average number of patients with BM at diagnosis from all cancer sites was approximately 3227. The site-specific IPs of BM at diagnosis were: lung (9.42%; 95% CI: 9.16-9.68%), esophageal (1.58%; 95% CI: 1.15-2.02%), kidney/renal pelvis (1.33%; 95% CI: 1.12-1.54%), skin melanoma (0.73%; 95% CI: 0.61-0.84%), colorectal (0.22%; 95% CI: 0.18-0.26%), and breast (0.21%; 95% CI: 0.17-0.24%). Approximately 76,546 lifetime BM cases (or 5.70% of selected fifteen primary cancers sites) were estimated to have occurred from the 2010-2017 cancer patient cohort. These findings reflect results of population analyses in the US and Denmark. We recommend improved standardization of the collection of BM data within the CCR.

Head and neck squamous cell carcinomas among males of the three largest Asian diasporas in the US, 2004-2013.

BACKGROUND: Head and neck squamous cell carcinomas (HNSCC) have not been fully examined in the Asian diasporas in the US, despite certain Asian countries having the highest incidence of specific HNSCCs. METHODS: National Cancer Database was used to compare 1046 Chinese, 887 South Asian (Indian/Pakistani), and 499 Filipino males to 156,927 Non-Hispanic White (NHW) males diagnosed with HNSCC between 2004-2013. Multinomial logistic regression was used to assess the association of race/ethnicity with two outcomes - site group and late-stage diagnosis. Temporal trends were explored for site groups and subsites. RESULTS: South Asians had a greater proportion of oral cavity cancer [OCC] compared to NHWs (59 % vs. 25 %; ORadj =7.3 (95 % CI: 5.9-9.0)). In contrast, Chinese (64 % vs. 9%; ORadj =34.0 (95 % CI: 26.5-43.6)) and Filipinos (47 % vs. 9%; ORadj =10.0 (95 % CI: 7.8-12.9)) had a greater proportion of non-oropharyngeal cancer compared to NHWs. All three Asian subgroups had a higher likelihood of being diagnosed by age 40 (14 % Chinese, 10 % South Asian and 8% Filipino compared to 3% in NHW; p < 0.001). Chinese males had lower odds of late-stage diagnosis, compared to NHWs. South Asian cases doubled from 2004 to 2013 largely due to an increase in OCC cases (34 cases in 2004 to 86 in 2013). CONCLUSION: Asian diasporas are at a higher likelihood of specific HNSCCs. Risk factors, screening and survival need to be studied further, and policy changes are needed to promote screening and to discourage high-risk habits in these Asian subgroups.

Clinical Uncertainty and Equipoise in the Management of Recurrent Glioblastoma.

BACKGROUND: A significant proportion of glioblastoma (GBM) patients are considered for repeat resection, but evidence regarding best management remains elusive. Our aim was to measure the degree of clinical uncertainty regarding reoperation for patients with recurrent GBM. METHODS: We first performed a systematic review of agreement studies examining the question of repeat resection for recurrent GBM. An electronic portfolio of 37 pathologically confirmed recurrent GBM patients including pertinent magnetic resonance images and clinical information was assembled. To measure clinical uncertainty, 26 neurosurgeons from various countries, training backgrounds, and years' experience were asked to select best management (repeat surgery, other nonsurgical management, or conservative), confidence in recommended management, and whether they would include the patient in a randomized trial comparing surgery with nonsurgical options. Agreement was evaluated using κ statistics. RESULTS: The literature review did not reveal previous agreement studies examining the question. In our study, agreement regarding best management of recurrent GBM was slight, even when management options were dichotomized (repeat surgery vs. other options; κ=0.198 [95% confidence interval: 0.133-0.276]). Country of practice, years' experience, and training background did not change results. Disagreement and clinical uncertainty were more pronounced within clinicians with (κ=0.167 [0.055-0.314]) than clinicians without neuro-oncology fellowship training (κ=0.601 [0.556-0.646]). A majority (51%) of responders were willing to include the patient in a randomized trial comparing repeat surgery with nonsurgical alternatives in 26/37 (69%) of cases. CONCLUSION: There is sufficient uncertainty and equipoise regarding the question of reoperation for patients with recurrent glioblastoma to support the need for a randomized controlled trial.

The Importance of Cancer Registry Linkage for Studying Rare Cancers in Prospective Cohorts.

Large prospective cohort studies may offer an opportunity to study the etiology and natural history of rare cancers. Cancer diagnoses in observational cohort studies are often self-reported. Little information exists on the validity of self-reported cancer diagnosis, especially rare cancers, in Canada. This study evaluated the validity of self-reported cancer diagnosis in Alberta's Tomorrow Project (ATP), a provincial cohort in Canada. ATP data were linked to the Alberta Cancer Registry (ACR). The first instance of self-reported cancer in a follow-up survey was compared to the first cancer diagnosis in the ACR after enrollment. The sensitivity and positive predictive value (PPV) were estimated for the reporting of cancer status, reporting of common or rare cancer, and reporting of site-specific cancer. Logistic regression analysis explored factors associated with false positive, false negative, and incorrect cancer site reporting. In the 30,843 ATP participants who consented to registry linkage, there were 810 primary cancer diagnoses in the ACR and 959 self-reports of first cancer post-enrollment, for a cancer status sensitivity of 92.1% (95% CI: 90.0-93.9) and PPV of 77.8% (95% CI: 75.0-80.4). Compared to common cancers, rare cancers had a lower sensitivity (62.8% vs. 89.6%) and PPV (35.8% vs. 84.5%). Participants with a rare cancer were more likely to report an incorrect site than those with a common cancer. Rare cancers were less likely to be captured by active follow-up than common cancers. While rare cancer research may be feasible in large cohort studies, registry linkage is necessary to capture rare cancer diagnoses completely and accurately.

A machine learning approach to predict ethnicity using personal name and census location in Canada.

BACKGROUND: Canada is an ethnically-diverse country, yet its lack of ethnicity information in many large databases impedes effective population research and interventions. Automated ethnicity classification using machine learning has shown potential to address this data gap but its performance in Canada is largely unknown. This study conducted a large-scale machine learning framework to predict ethnicity using a novel set of name and census location features. METHODS: Using census 1901, the multiclass and binary class classification machine learning pipelines were developed. The 13 ethnic categories examined were Aboriginal (First Nations, Métis, Inuit, and all-combined)), Chinese, English, French, Irish, Italian, Japanese, Russian, Scottish, and others. Machine learning algorithms included regularized logistic regression, C-support vector, and naïve Bayes classifiers. Name features consisted of the entire name string, substrings, double-metaphones, and various name-entity patterns, while location features consisted of the entire location string and substrings of province, district, and subdistrict. Predictive performance metrics included sensitivity, specificity, positive predictive value, negative predictive value, F1, Area Under the Curve for Receiver Operating Characteristic curve, and accuracy. RESULTS: The census had 4,812,958 unique individuals. For multiclass classification, the highest performance achieved was 76% F1 and 91% accuracy. For binary classifications for Chinese, French, Italian, Japanese, Russian, and others, the F1 ranged 68-95% (median 87%). The lower performance for English, Irish, and Scottish (F1 ranged 63-67%) was likely due to their shared cultural and linguistic heritage. Adding census location features to the name-based models strongly improved the prediction in Aboriginal classification (F1 increased from 50% to 84%). CONCLUSIONS: The automated machine learning approach using only name and census location features can predict the ethnicity of Canadians with varying performance by specific ethnic categories.

Ovarian Cancer in Women of African Ancestry (OCWAA) consortium: a resource of harmonized data from eight epidemiologic studies of African American and white women.

PURPOSE: Although the incidence rate of epithelial ovarian cancer (EOC) is somewhat lower in African American (AA) than white women, survival is worse. The Ovarian Cancer in Women of African Ancestry (OCWAA) consortium will overcome small, study-specific sample sizes to better understand racial differences in EOC risk and outcomes. METHODS: We harmonized risk factors and prognostic characteristics from eight U.S. STUDIES: the North Carolina Ovarian Cancer Study (NCOCS), the Los Angeles County Ovarian Cancer Study (LACOCS), the African American Cancer Epidemiology Study (AACES), the Cook County Case-Control Study (CCCCS), the Black Women's Health Study (BWHS), the Women's Health Initiative (WHI), the Multiethnic Cohort Study (MEC), and the Southern Community Cohort Study (SCCS). RESULTS: Determinants of disparities for risk and survival in 1,146 AA EOC cases and 2,922 AA controls will be compared to 3,368 white EOC cases and 10,270 white controls. Analyses include estimation of population-attributable risk percent (PAR%) by race. CONCLUSION: OCWAA is uniquely positioned to study the epidemiology of EOC in AA women compared with white women to address disparities. Studies of EOC have been underpowered to address factors that may explain AA-white differences in the incidence and survival. OCWAA promises to provide novel insight into disparities in ovarian cancer.

Malignant primary brain and other central nervous system tumors diagnosed in Canada from 2009 to 2013.

BACKGROUND: We present a national surveillance report on malignant primary brain and other central nervous system (CNS) tumors diagnosed in the Canadian population in 2009-2013. METHODS: Patients were identified through the Canadian Cancer Registry, an administrative dataset that includes cancer incidence data from all provinces/territories in Canada. Tumor types were classified by site and histology using the definitions from the Central Brain Tumor Registry of the United States (CBTRUS). Incidence rates (IRs) and 95% confidence intervals (CIs) were calculated per 100000 person-years (py) and age-standardized to the 2011 Canadian population for comparisons within Canada and to the 2000 United States population for comparisons with the US. RESULTS: Overall, 12515 malignant brain and other CNS tumors were diagnosed in the Canadian population in 2009-2013 (IR: 8.71/100000 py; 95% CI: 8.56, 8.86); 7085 were among males (IR: 10.06/100000 py; 95% CI: 9.82, 10.29) and 5430 among females (IR: 7.41/100000 py; 95% CI: 7.22, 7.61). Of these, 12115 were classifiable according to histological subgroups defined by CBTRUS. The most common histology was glioblastoma (IR: 4.06/100000 py; 95% CI: 3.95, 4.16). Among those aged 0-19 years, 1130 malignant brain and CNS tumors were diagnosed in 2009-2013 (IR: 3.36/100000 py; 95% CI: 3.16, 3.56). The most common histology among the pediatric population was embryonal tumor (IR: 0.74/100000 py; 95% CI: 0.65, 0.84). CONCLUSIONS: These data represent an initial detailed report on the frequency and distribution of primary malignant brain and other CNS tumors diagnosed in the Canadian population in 2009-2013. The reported distributions of tumor diagnoses by sex and age reflected expected patterns based on the literature from similar populations. A report incorporating data on nonmalignant primary brain tumors is forthcoming.

Application of mutagen sensitivity assay in a glioma case-control study.

Few risk factors for glioma have been identified other than ionizing radiation. The alkylating agent acrylamide is a compound found in both occupational and the general environment and identified as one of the forty known or suspected neurocarcinogens in animal models. The mutagen sensitivity assay (MSA) has been used to indirectly show reduced DNA repair capacity upon exposure to ionizing radiation in those with glioma compared to controls. In this study, MSA was used to assess its applicability to a glioma case-control study and to test the hypothesis that subjects with glioma may have lower DNA repair capacity after exposure to selected potential human neurocarcinogens (i.e. acrylamide), compared to controls. Approximately 50 case and 50 control subjects were identified from a clinic-based study that investigated environmental risk factors for glioma, who completed an exposure survey, and had frozen immortalized lymphocytes available. A total of 50 metaphase spreads were read and reported for each participant. The association of case-control status with MSA for acrylamide, i.e. breaks per spread, was examined by multivariable logistic regression models. The mean number of breaks per slide was similar between hospital-based controls and cases. In addition, case-control status or exposure categories were not associated with the number of breaks per spread. Although the MSA has been shown as a useful molecular epidemiology tool for identifying individuals at higher risk for cancer, our data do not support the hypothesis that glioma patients have reduced DNA repair capacity in response to exposure to acrylamide. Further research is needed before the MSA is utilized in large-scale epidemiological investigations of alkylating agents.

Measures of economic advantage associated with HPV-positive head and neck cancers among non-Hispanic black and white males identified through the National Cancer Database.

BACKGROUND: National trends show dramatic increases in the incidence of HPV-related head and neck squamous cell carcinomas (HNSCCs) among black and white males. Using cases identified through the National Cancer Data Base, we assessed factors associated with HPV 16- or 16/18 positive HNSCCs among non-Hispanic black and white males diagnosed in the U.S. between 2009 and 2013. METHODS: This sample included 21,524 HNSCCs with known HPV status. Adjusted relative risks (RRs) and 95% confidence intervals (CIs) were estimated using log-binomial regression. RESULTS: Compared to those with HPV-negative tumors, male patients diagnosed with HPV-positive HNSCCs were non-Hispanic white, younger at diagnosis, lived in zip-code areas with higher median household income and higher educational attainment, had private health insurance and no reported comorbidities at diagnosis. Although the risk of HPV-positive HNSCCs increased with measures of higher area-level socioeconomic status, the effect was stronger for non-Hispanic black males (RRAdjusted=1.76, 95% CI 1.49-2.09) than for whites (RRAdjusted=1.12, 95% CI 1.08-1.16). The peak age for diagnosis of HPV-positive HNSCCs occurred in those diagnosed at 45-49 years (RRAdjusted=1.57, 95% CI 1.42-1.73). Oropharyngeal tumors were strongly associated with HPV-positivity (RRAdjusted=4.32, 95% CI 4.03-4.63). In the analysis restricted to oropharyngeal anatomic sites, similar patterns persisted. CONCLUSION: In our analysis, measures of economic advantage were associated with an increased risk of HPV-positive HNSCCs. In order to develop effective interventions, greater understanding of the risk factors for HPV-positive HNSCCs is needed among both high-risk males and their healthcare providers.

The effect of time on racial differences in epithelial ovarian cancer (OVCA) diagnosis stage, overall and by histologic subtypes: a study of the National Cancer Database.

PURPOSE: Previous studies assessing racial and ethnic differences in ovarian cancer (OVCA) diagnosis stage fail to present subtype-specific results and provide historic data on cases diagnosed between 10 and 20 years ago. The purpose of this analysis is to assess non-Hispanic Black (NHB) and non-Hispanic White (NHW) differences in late-stage diagnosis including; (1) factors associated with late-stage diagnosis of invasive epithelial OVCA overall and by histologic subtypes, (2) potential changes across time and (3) current patterns of trends in a national cancer registry in the USA and Puerto Rico between 1998 and 2011. METHODS: NHB and NHW OVCA cases were derived from the National Cancer Database (NCDB). Diagnosis stage was analyzed as a dichotomous and a four level-category variable, respectively; early (stages I and II; localized) versus late (stages III and IV; regional and distant) and stages I, II, III and IV. Diagnosis period was trichotomized (1998-2002, 2003-2007, 2008-2011). Racial differences in stage were tested using Chi-square statistics. Odds ratios (OR) and 95 % confidence intervals (95 % CI) were estimated using multivariable binomial and generalized ordered logistic regressions. Interactions between race and diagnosis period were evaluated. RESULTS: Between 1998 and 2011, 11,562 (7.8 %) NHB and 137,106 (92.2 %) NHW were diagnosed with OVCA. In adjusted models, NHB were significantly more likely diagnosed with late-stage OVCA than NHW (ORadj 1.26, 95 % CI 1.19-1.33). Interaction between race and diagnosis period was marginally significant (p value = 0.09), with racial differences in stage decreasing over time (1998-2002: ORadj 1.36, 95 % CI 1.23-1.49; 2003-2007: ORadj 1.27, 95 % CI 1.15-1.39; 2008-2011; ORadj 1.15, 95 % CI 1.05-1.27). NHB were also more likely to be diagnosed with stage 4 high-grade serous (ORadj 1.46, 95 % CI 1.22-1.74), clear cell (ORadj 2.71, 95 % CI 1.94-3.79) and mucinous (ORadj 2.78, 95 % CI 2.24-3.46) carcinomas than NHW. CONCLUSIONS: Racial differences in late-stage OVCA diagnosis exist; however, these differences are decreasing with time. Within NCDB, NHB are significantly more likely diagnosed with late-stage OVCA and more specifically high-grade serous, clear cell and mucinous carcinomas than NHW.

Racial differences in head and neck squamous cell carcinomas among non-Hispanic black and white males identified through the National Cancer Database (1998-2012).

PURPOSE: Head and neck squamous cell carcinoma (HNSCC) incidence is increasing, and evidence suggests survival disparities between non-Hispanic (nH) black and white males. However, temporal changes in HNSCCs and factors contributing to survival differences have not been examined at the national level. METHODS: National Cancer Database (NCDB) cases were used to evaluate temporal trends in HNSCC anatomical sites and site groupings (i.e., oral cavity, oropharyngeal, non-oropharyngeal), and to estimate incidence ratios (IRs) comparing nH black and white males in demographic and clinical characteristics. RESULTS: Between 1998 and 2012, 18,443 (11 %) nH black males and 145,611 (89 %) nH white males were diagnosed with HNSCCs. Cases rose from 9094 diagnosed in 1998 to 13,838 in 2012, driven by increases in oropharyngeal tumors, particularly tumors of the tonsil and tongue. Annual percent changes in nH black males and nH white males were 1.93 and 3.17, respectively. Additionally, nH black males had higher incidence of the more aggressive non-oropharyngeal tumors (p < .0001) and distant-stage tumors (76 vs. 64 %, p < .0001). However, nH white males had higher incidence of high-risk HPV types (IRs range from 1.68, 95 % CI 1.50-1.88 in oropharyngeal tumors to 3.03, 95 % CI 1.11-8.25 in non-oropharyngeal tumors). CONCLUSIONS: Incidence of oropharyngeal tumors has risen in both nH black and white males. However, nH white males have higher incidence of HPV, and nH black males have higher incidence of more aggressive and advanced HNSCCs. Racial differences in clinical characteristics associated with poorer survival exist, and future studies should determine factors associated with these differences.

Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome.

To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events >2 Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases.

Canadian brain cancer survival rates by tumour type and region: 1992-2008.

OBJECTIVES: To investigate patterns of survival among brain cancer patients in Canada. METHODS: Canadian Cancer Registry data were obtained for all patients with first-ever primary malignant brain tumours diagnosed between 1992 and 2008 (n = 38,095). Follow-up ended with patient death or December 31, 2008, whichever occurred first. Crude Kaplan-Meier estimates were calculated at one, two and five years post-diagnosis. Cox proportional hazard models were used to obtain adjusted hazard ratios by region for major histology types. A time-specific generalized linear model was used to obtain 5-year survival estimates for specific age group, sex and region for major histology types. RESULTS: The overall five-year survival rate was 27%. No significant difference in survival rate over time is observed. The highest 5-year survival rate was 65% (95% CI: 62.5%-67.4%) for oligodendrogliomas and the lowest was 4.0% (95% CI: 3.7%-4.3%) for glioblastomas. Compared to Ontario, the adjusted 5-year glioblastoma survival estimates were lower in British Columbia, Alberta and the Prairie provinces (Manitoba and Saskatchewan), while the survival estimates were lower in all other regions for diffuse astrocytoma, and lower in Manitoba and Saskatchewan for anaplastic astrocytomas. Estimates were significantly higher for oligodendrogliomas in Alberta, and for anaplastic oligodendrogliomas in Alberta and Quebec (p < 0.05). CONCLUSION: These data are consistent with previous literature in observing higher survival rates at younger ages, in female patients and for tumours with mixed oligo components. There is a need to further explore the underlying reasons for the observed variation in survival rates by region in an effort to improve the prognosis of brain cancer in the Canadian patient population.

Analgesic use and risk of renal cell carcinoma: A case-control, cohort and meta-analytic assessment.

Analgesics are the most commonly consumed drugs worldwide. Evidence that analgesics increase kidney cancer risk has been mixed. We investigated the association between renal cell carcinoma (RCC) and analgesic use in a large population-based case-control study and a post-trial observational cohort study. Findings were used to update a recent meta-analytic review. We analyzed data from 1,217 RCC cases and 1,235 controls in the US Kidney Cancer Study and 98,807 participants in the US Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO: n = 137 RCCs). Self-reported acetaminophen, aspirin and nonsteroid anti-inflammatory drug (NSAID) use and duration information was assessed in relation to RCC. For the US Kidney Cancer Study, we calculated odds ratios (ORs) and 95% confidence intervals (CIs) using unconditional logistic regression. For PLCO, we computed hazard ratios (HRs) and 95%CIs using Cox regression. Among case-control participants, RCC risk was associated with over-the-counter acetaminophen use (OR = 1.35, 95%CI = 1.01-1.83). There was a positive trend with increasing duration (p-trend = 0.01), with a two-fold risk for use ≥10 years (OR = 2.01, 95%CI = 1.30-3.12). No association with prescription acetaminophen use was detected. In PLCO, acetaminophen use was also associated with increased RCC risk (HR = 1.68, 95%CI = 1.19-2.39), although elevated risk was absent among the few long-term users. No association with RCC risk was detected for aspirin or NSAIDs use in either study. An association between acetaminophen use and kidney cancer was supported by meta-analytic cohort (n = 4; summary relative risk = 1.34; 95%CI = 1.13-1.59; p-heterogeneity = 0.40) and case-control (n = 9, summary OR = 1.20; 95%CI = 1.01-1.42; p-heterogeneity = 0.05) findings. In brief, acetaminophen use may increase the risk of developing RCC.

History of chickenpox in glioma risk: a report from the glioma international case-control study (GICC).

Varicella 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.

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.

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.