Number of Older Biological Siblings and Early-Onset Colorectal Cancer Risk.

Colorectal cancer (CRC) is the third most common cancer in the United States.1 Although CRC incidence has declined in individuals >50 years, incidence is rising in adults <50 years (early onset).1 By 2027, CRC is projected to become the leading cause of cancer mortality in US adults <50 years.2 To combat the rising incidence of early onset CRC (EOCRC), national guidelines recently lowered the screening age from 50 to 45 years for average-risk individuals.3 Understanding the risk profile of EOCRC can help combat the rising burden in young adults, especially in those ineligible for screening.

Hypertension and risk of endometrial cancer: a pooled analysis in the Epidemiology of Endometrial Cancer Consortium (E2C2).

BACKGROUND: The incidence rates of endometrial cancer (EC) are increasing, which may partly be explained by the rising prevalence of obesity, an established risk factor for EC. Hypertension, another component of metabolic syndrome, is also increasing in prevalence, and emerging evidence suggests that it may be associated with the development of certain cancers. The role of hypertension independent of other components of metabolic syndrome in the etiology of EC remains unclear. In this study we evaluated hypertension as an independent risk factor for EC and whether this association is modified by other established risk factors. METHODS: We included 15,631 EC cases and 42,239 controls matched on age, race, and study-specific factors from 29 studies in the Epidemiology of Endometrial Cancer Consortium. We used multivariable unconditional logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) to evaluate the association between hypertension and EC and whether this association differed by study design, race/ethnicity, body mass index, diabetes status, smoking status, or reproductive factors. RESULTS: Hypertension was associated with an increased risk of EC (OR=1.14, 95% CI:1.09-1.19). There was significant heterogeneity by study design (Phet<0.01), with a stronger magnitude of association observed among case-control vs. cohort studies. Stronger associations were also noted for pre-/peri-menopausal women and never users of postmenopausal hormone therapy. CONCLUSIONS: Hypertension is associated with EC risk independently from known risk factors. Future research should focus on biologic mechanisms underlying this association. IMPACT: This study provides evidence that hypertension may be an independent risk factor for EC.

Clinical and descriptive characteristics associated with high-grade meningioma in a large clinical series.

PURPOSE: We studied 571 patients with intracranial meningioma for clinical characteristics and tumor location associated with high grade meningioma (WHO II/III). MATERIALS AND METHODS: Patients were participants in a multicentre epidemiologic study of risk factors for primary brain tumors including meningioma recruited from September 2005 to November 2019. We included patients 18 or older with a recent diagnosis of a primary intracranial meningioma of any subtype (ICD9/10: 9530-0, 9531-0, 9532-0, 9537-0, 9533-0, 9534-0, 9530-0, 9538-1, 9538-3) who were enrolled at neuro-oncology and neuro-surgery clinics in the southeastern U.S. RESULTS: The median patient age was 58 years (IQR: 48-68) and the majority of patients were female (n = 415; 72.7%) and Caucasian (n = 516; 90.4%). Most patients were symptomatic (n = 460; 80.6%) and their tumours more commonly occurred in a non-skull base location (n = 298; 52.2%). A total of 86 patients (15.0%) had a WHO grade II/III meningioma. Compared to patients with WHO grade I tumours, patients with WHO II/III meningiomas were over 3-times more likely to be male (odds ratio (OR): 3.25; 95% confidence interval (CI): 1.98, 5.35) adjusting for age, race, symptomatic presentation, and skull-based location. Moreover, a WHO grade II/III meningioma was substantially less likely to be observed in asymptomatic patients (OR: 0.15, 95% CI: 0.04, 0.42), and in patients with a skull-based tumour (OR: 0.40, 95% CI: 0.24, 0.66), adjusting for other factors. Male gender, symptomatic tumour, and a non-skull base location were independently associated with WHO grade II/III meningioma. CONCLUSION: These findings may shed additional light on the underlying pathogenesis of meningioma.

Validating a semi-quantitative food frequency questionnaire to assess regional diet in a study of cancer in South West Nigeria.

PURPOSE: Cancer burden is rising rapidly in Nigeria, the most populous country in sub-Saharan Africa; this trend may in part be attributable to diet. We developed and validated a semi-quantitative food frequency questionnaire (FFQ) to assess regional diet in Nigeria. METHODS: We recruited 68 adult participants from rural and urban settings in South West Nigeria. We developed an FFQ administered at baseline and assessed its validity using 3 dietary recalls (baseline, 7 days post baseline, 3 months post baseline). We calculated Spearman's rank correlation coefficients and energy-adjusted de-attenuated correlation coefficients for food items and macronutrients. We evaluated cross-classification using quartiles of macronutrient intake. RESULTS: Energy-adjusted de-attenuated food item correlations between the FFQ and dietary recalls ranged from -0.08 (smoked beef/goat) to 0.73 (fried snacks) for the average intake from the first 2 recalls (2DR) and from -0.05 (smoked beef/goat) to 0.75 (smoked fish) for the average of all 3 recalls (3DR). Macronutrient correlations ranged from 0.15 (fat) to 0.37 (fiber) for the 2DR and from 0.08 (fat) to 0.41 (carbohydrates) for the 3DR. The percent of participants classified in the same quartile ranged from 16.4% (fat) to 32.8% (fiber, protein) for the 2DR and from 25.6% (fat) to 34.9% (carbohydrates) for the 3DR. Agreement improved when including adjacent quartiles, from 65.5% (carbohydrates) to 70.5% (fat, fiber) for the 2DR and from 62.8% (protein) to 76.8% (carbohydrate) for the 3DR. CONCLUSION: Our semi-quantitative FFQ was reasonably valid for ranking intake of certain foods and macronutrients in adults in South West Nigeria.

Differential trends in rising endometrial cancer incidence by age, race, and ethnicity.

Endometrial cancer (EC) incidence is on the rise. Although early-onset endometrial cancer (EOEC; age at diagnosis <50 years) is relatively uncommon, the incidence of EOEC has been reportedly increasing in recent decades. However, the rising EOEC has not been thoroughly described with regard to the racial and ethnic disparities and compared with late-onset EC (age at diagnosis ≥50 years). We used the Cancer in North America (CiNA) Analytic File, 1995-2018, from the North American Association of Central Cancer Registries, which allowed us to examine trends in invasive EC incidence by racial and ethnic groups and by age at diagnosis. We found striking differences for demographic and tumor characteristics as well as racial and ethnic patterns and time trends in EC incidence between EOEC and late-onset EC. The faster increases in EOEC incidence rates, especially among non-White women, mirror similar observations in other cancers, pointing to a possible link with rising obesity epidemic in younger generations.

Association Between Polycystic Ovary Syndrome and Risk of Pancreatic Cancer.

This case-control study sought to confirm the exploratory finding of an association between polycystic ovary syndrome and risk of pancreatic cancer.

Sleep Duration, Chronotype, and Insomnia and the Risk of Lung Cancer: United Kingdom Biobank Cohort.

BACKGROUND: Relationships between sleep duration, chronotype, insomnia, and lung cancer risk have not been comprehensively examined. Interrelations between sleep traits on the risk of lung cancer have not been assessed. We aimed to examine sleep traits with lung cancer risk. METHODS: Participants were recruited between 2006 and 2010 and followed through November 30, 2020. We included 382,966 participants (3,664 incident lung cancer) in analysis. Cox proportional hazards models estimated HRs and 95% confidence intervals (CI) for associations between sleep duration, chronotype, and insomnia symptoms and lung cancer risk. Joint effects analyses were examined between sleep duration and three traits (chronotype, insomnia, and daytime napping). Nonlinear associations between sleep duration and lung cancer risk were assessed in restricted cubic spline analysis. RESULTS: Longer sleep (>8 hours) was positively associated with lung cancer risk compared with normal sleep duration (7-8 hours; HR = 1.22; 95% CI, 1.10-1.36). Frequent insomnia symptoms increased the risk of lung cancer compared with never/rarely experiencing symptoms (HR = 1.16; 95% CI, 1.05-1.28). Joint effects between sleep duration and chronotype, and sleep duration and insomnia symptoms were observed. In analysis excluding participants reporting shift work at baseline, evening chronotypes ("slight," "definite") were at a greater risk of lung cancer compared with definite morning chronotype (HR = 1.17; 95% CI, 1.06-1.28 and HR = 1.37; 95% CI, 1.21-1.54, respectively). CONCLUSIONS: Sleep traits such as long sleep duration, frequent insomnia symptoms, and definite evening chronotype may be risk factors for lung cancer. Joint effects should be further investigated. IMPACT: Sleep traits may be risk factors of lung cancer.

Association of magnesium intake and vitamin D status with cognitive function in older adults: an analysis of US National Health and Nutrition Examination Survey (NHANES) 2011 to 2014.

PURPOSE: Reduced cognitive function associated with aging has gained increasing attention as the US population ages. Magnesium plays a critical role in vitamin D biosynthesis and metabolism; and deficiencies in magnesium and vitamin D show associations with poor cognition. However, no study has examined their interaction. This study aimed to evaluate the associations of magnesium intake and serum 25-hydroxyvitamin D (25(OH)D) concentrations, indicating vitamin D status, with cognition, and interaction between these nutrients in older adults. METHODS: Based on the National Health and Nutrition Survey (NHANES) 2011-2014, the study included 2466 participants aged ≥ 60 years who completed the Digit Symbol Substitution Test (DSST) and had data available on serum 25(OH)D and magnesium intake. Cognitive impairment was defined as a DSST score lower than the lowest quartile. Serum 25(OH)D concentrations were measured by HPLC-tandem mass spectrometry. RESULTS: Higher total magnesium intake was independently associated with higher DSST scores (highest quartile vs lowest: ß = 4.34, 95% CI 1.14-7.54). The association of total magnesium intake with high DSST score was primarily observed among women, non-Hispanic whites, physically active participants and those with sufficient vitamin D status, although the interactions were not significant. The odds of cognitive impairment was reduced with increasing intake of total magnesium (p trend < 0.01) and higher level of serum 25(OH)D (p trend = 0.05). CONCLUSIONS: Findings suggest that high magnesium intake alone may improve cognitive function in older adults, and the association may be stronger among subjects with sufficient vitamin D status. Further studies are needed to confirm these findings.

Association of serum levels of antioxidant micronutrients with mortality in US adults: National Health and Nutrition Examination Survey 1999-2002.

OBJECTIVE: To examine associations between serum antioxidant levels and mortality (all-cause, cancer and CVD) among US adults. DESIGN: We examined the risk of death from all-cause and cause-specific mortality associated with serum antioxidant (vitamin E and carotenoids) and vitamin A levels using Cox regression models to estimate hazards ratios (HR) and 95 % CI. SETTING: The National Health and Nutrition Examination Survey (NHANES) 1999-2002 was followed up through 31 December 2015. PARTICIPANTS: The NHANES 1999-2002 cohort included 8758 participants aged ≥ 20 years. Serum carotenoid levels were only assessed for the 1999-2000 cycle. Therefore, sample size for each assessed antioxidant ranged from 4633 to 8758. RESULTS: Serum vitamin E level was positively associated with all-cause mortality (HR = 1·22, 95 % CI 1·04, 1·43, highest v. lowest quartile). No other antioxidants were associated with mortality in overall analysis. In race/ethnicity-specific analyses, high vitamin E and α-tocopherol levels were associated with increased risk of all-cause mortality among non-Hispanic Whites. Among non-Hispanic Blacks, serum α-tocopherol level was associated with decreased risk of cancer mortality (HR = 0·30, 95 % CI 0·12, 0·75, third v. first quartile) and total carotenoid levels with reduced risk of CVD mortality (HR = 0·26; 95 % CI 0·07, 0·97, second v. lowest quartile). Hispanics with high ß-carotene levels had reduced risk of CVD mortality. CONCLUSIONS: Serum antioxidant levels may be related to mortality; these associations may differ by race/ethnicity and appeared to be non-linear for all-cause and cause-specific mortality. Further studies are needed to confirm our results.

Understanding the Interplay Between Health Disparities and Epigenomics.

Social epigenomics has emerged as an integrative field of research focused on identification of socio-environmental factors, their influence on human biology through epigenomic modifications, and how they contribute to current health disparities. Several health disparities studies have been published using genetic-based approaches; however, increasing accessibility and affordability of molecular technologies have allowed for an in-depth investigation of the influence of external factors on epigenetic modifications (e.g., DNA methylation, micro-RNA expression). Currently, research is focused on epigenetic changes in response to environment, as well as targeted epigenetic therapies and environmental/social strategies for potentially minimizing certain health disparities. Here, we will review recent findings in this field pertaining to conditions and diseases over life span encompassing prenatal to adult stages.

Sex-specific impact of patterns of imageable tumor growth on survival of primary glioblastoma patients.

BACKGROUND: Sex is recognized as a significant determinant of outcome among glioblastoma patients, but the relative prognostic importance of glioblastoma features has not been thoroughly explored for sex differences. METHODS: Combining multi-modal MR images, biomathematical models, and patient clinical information, this investigation assesses which pretreatment variables have a sex-specific impact on the survival of glioblastoma patients (299 males and 195 females). RESULTS: Among males, tumor (T1Gd) radius was a predictor of overall survival (HR = 1.027, p = 0.044). Among females, higher tumor cell net invasion rate was a significant detriment to overall survival (HR = 1.011, p < 0.001). Female extreme survivors had significantly smaller tumors (T1Gd) (p = 0.010 t-test), but tumor size was not correlated with female overall survival (p = 0.955 CPH). Both male and female extreme survivors had significantly lower tumor cell net proliferation rates than other patients (M p = 0.004, F p = 0.001, t-test). CONCLUSION: Despite similar distributions of the MR imaging parameters between males and females, there was a sex-specific difference in how these parameters related to outcomes.

Defending against the Novel Coronavirus (COVID-19) outbreak: How can the Internet of Things (IoT) help to save the world?

•IoT within infectious disease epidemiology is an emerging field of research, however the ubiquitous availability of smart technologies, as well as increased risks of infectious disease spread through the globalization and interconnectedness of the world necessitates its use for predicting, preventing and controlling emerging infectious diseases.•Considering the present situation in China, IoT based smart disease surveillance systems have the potential to be a major breakthrough in efforts to control the current pandemic. With much of the infrastructure itself in place already (i.e. smartphones, wearable technologies, internet access) the role this technology can have in limiting the spread of the pandemic involves only the collection and analysis of data already gathered.•More research must be carried out for the development of automated and effective alert systems to provide early and timely detection of outbreaks of such diseases in order to reduce morbidity mortality and prevent global spread.

The SARS, MERS and novel coronavirus (COVID-19) epidemics, the newest and biggest global health threats: what lessons have we learned?

OBJECTIVES: To provide an overview of the three major deadly coronaviruses and identify areas for improvement of future preparedness plans, as well as provide a critical assessment of the risk factors and actionable items for stopping their spread, utilizing lessons learned from the first two deadly coronavirus outbreaks, as well as initial reports from the current novel coronavirus (COVID-19) epidemic in Wuhan, China. METHODS: Utilizing the Centers for Disease Control and Prevention (CDC, USA) website, and a comprehensive review of PubMed literature, we obtained information regarding clinical signs and symptoms, treatment and diagnosis, transmission methods, protection methods and risk factors for Middle East respiratory syndrome (MERS), severe acute respiratory syndrome (SARS) and COVID-19. Comparisons between the viruses were made. RESULTS: Inadequate risk assessment regarding the urgency of the situation, and limited reporting on the virus within China has, in part, led to the rapid spread of COVID-19 throughout mainland China and into proximal and distant countries. Compared with SARS and MERS, COVID-19 has spread more rapidly, due in part to increased globalization and the focus of the epidemic. Wuhan, China is a large hub connecting the North, South, East and West of China via railways and a major international airport. The availability of connecting flights, the timing of the outbreak during the Chinese (Lunar) New Year, and the massive rail transit hub located in Wuhan has enabled the virus to perforate throughout China, and eventually, globally. CONCLUSIONS: We conclude that we did not learn from the two prior epidemics of coronavirus and were ill-prepared to deal with the challenges the COVID-19 epidemic has posed. Future research should attempt to address the uses and implications of internet of things (IoT) technologies for mapping the spread of infection.

Methylmercury exposure, genetic variation in metabolic enzymes, and the risk of glioma.

Methylmercury (MeHg) is an environmental neurotoxin with human exposure mainly from dietary intake of contaminated fish. Exposure to MeHg has been implicated in neurological damage, but research on its role in cancers, specifically glioma, is limited. In a glioma case-control study, we examined associations between toenail mercury (Hg) and glioma risk. We also examined genetic polymorphisms in 13 genes related to MeHg metabolism for association with glioma risk; genetic associations were also studied in the UK Biobank cohort. Median toenail Hg in cases and controls, respectively, was 0.066 µg/g and 0.069 µg/g (interquartile range (IQR): 0.032-0.161 and 0.031-0.150 µg/g). Toenail Hg was not found to be significantly associated with glioma risk (Odds Ratio: 1.02; 95% Confidence Interval: 0.91, 1.14; p = 0.70 in analysis for ordinal trend with increasing quartile of toenail MeHg). No genetic variant was statistically significant in both of the studies; one variant, rs11859163 (MMP2) had a combined p-value of 0.02 though it was no longer significant after adjustment for multiple testing (Bonferroni corrected p = 1). This study does not support the hypothesis that exposure to MeHg plays a role in the development of glioma at levels of exposure found in this study population.

Medical Cannabis Use in Glioma Patients Treated at a Comprehensive Cancer Center in Florida.

Background: Glioma is a devastating primary tumor of the central nervous system with difficult-to-manage symptoms. Cannabis products have been postulated to potentially benefit glioma patients. Recent state legalization allowed investigators an opportunity to study glioma patients' adoption of medical marijuana (MM). Objective: Our goals were to: (1) determine the prevalence of marijuana use, both through physician recommendation and self-medication, and (2) evaluate its perceived risks and benefits in glioma patients. Design: Self-report data were collected and descriptive analyses were conducted. Setting/Subjects: Participants were adult, English-speaking patients undergoing treatment for primary non-recurrent malignant glioma in neuro-oncology clinics at an NCI-designated Comprehensive Cancer Center. Measurements: The survey on MM was adapted from previous research and included questions on knowledge and attitudes toward MM; use, frequency, type, and sourcing of MM; and reasons for use of MM and perceived symptom relief among users. Results: A total of 73 patients were surveyed. The majority of participants were aware that MM was legal in the state, and most reported learning of this through the media. Over 70% of participants reported having considered using MM, and a third reported using marijuana products after their diagnosis. Most received recommendations from friends/family rather than a medical provider, and only half of the users had obtained a physician's recommendation. Users generally reported benefits. Conclusions: With the increasing national conversation that accompanies legalization, glioma patients are pursuing marijuana for the treatment for their symptoms. More research and education is needed to bring health care providers into the conversation.

Multiparameter MRI Predictors of Long-Term Survival in Glioblastoma Multiforme.

Standard-of-care multiparameter magnetic resonance imaging (MRI) scans of the brain were used to objectively subdivide glioblastoma multiforme (GBM) tumors into regions that correspond to variations in blood flow, interstitial edema, and cellular density. We hypothesized that the distribution of these distinct tumor ecological "habitats" at the time of presentation will impact the course of the disease. We retrospectively analyzed initial MRI scans in 2 groups of patients diagnosed with GBM, a long-term survival group comprising subjects who survived >36 month postdiagnosis, and a short-term survival group comprising subjects who survived ≤19 month postdiagnosis. The single-institution discovery cohort contained 22 subjects in each group, while the multi-institution validation cohort contained 15 subjects per group. MRI voxel intensities were calibrated, and tumor voxels clustered on contrast-enhanced T1-weighted and fluid-attenuated inversion-recovery (FLAIR) images into 6 distinct "habitats" based on low- to medium- to high-contrast enhancement and low-high signal on FLAIR scans. Habitat 6 (high signal on calibrated contrast-enhanced T1-weighted and FLAIR sequences) comprised a significantly higher volume fraction of tumors in the long-term survival group (discovery cohort, 35% ± 6.5%; validation cohort, 34% ± 4.8%) compared with tumors in the short-term survival group (discovery cohort, 17% ± 4.5%, P < .03; validation cohort, 16 ± 4.0%, P < .007). Of the 6 distinct MRI-defined habitats, the fractional tumor volume of habitat 6 at diagnosis was significantly predictive of long- or short-term survival. We discuss a possible mechanistic basis for this association and implications for habitat-driven adaptive therapy of GBM.

Toenail selenium, genetic variation in selenoenzymes and risk and outcome in glioma.

BACKGROUND: Selenium is an essential trace element obtained through diet that plays a critical role in DNA synthesis and protection from oxidative damage. Selenium intake and polymorphisms in selenoproteins have been linked to the risk of certain cancers though data for glioma are sparse. METHODS: In a case-control study of glioma, we examined the associations of selenium in toenails and genetic variants in the selenoenzyme pathway with the risk of glioma and patient survival. A total of 423 genetic variants in 29 candidate genes in the selenoenzyme pathway were studied in 1547 glioma cases and 1014 healthy controls. Genetic associations were also examined in the UK Biobank cohort comprised of 313,868 persons with 322 incident glioma cases. Toenail selenium was measured in a subcohort of 300 glioma cases and 300 age-matched controls from the case-control study. RESULTS: None of the 423 variants studied were consistently associated with glioma risk in the case-control and cohort studies. Moreover, toenail selenium in the case-control study had no significant association with glioma risk (p trend = 0.70) or patient survival among 254 patients with high grade tumors (p trend = 0.70). CONCLUSION: The present study offers no support for the hypothesis that selenium plays a role in the onset of glioma or patient outcome.

Handedness and the risk of glioma.

Gliomas are the most common type of malignant primary brain tumor and few risk factors have been linked to their development. Handedness has been associated with several pathologic neurological conditions such as schizophrenia, autism, and epilepsy, but few studies have evaluated a connection between handedness and risk of glioma. In this study, we examined the relationship between handedness and glioma risk in a large case-control study (1849 glioma cases and 1354 healthy controls) and a prospective cohort study (326,475 subjects with 375 incident gliomas). In the case-control study, we found a significant inverse association between left handedness and glioma risk, with left-handed persons exhibiting a 35% reduction in the risk of developing glioma [odds ratio (OR) = 0.65, 95% confidence interval (CI) 0.51-0.83] after adjustment for age, gender, race, education, and state of residence; similar inverse associations were observed for GBM (OR = 0.69, 95% CI 0.52-0.91), and non-GBM (OR = 0.59, 95% CI 0.42-0.82) subgroups. The association was consistent in both males and females, and across age strata, and was observed in both glioblastoma and in lower grade tumors. In the prospective cohort study, we found no association between handedness and glioma risk (hazards ratio = 0.92, 95% CI 0.67-1.28) adjusting for age, gender, and race. Further studies on this association may help to elucidate mechanisms of pathogenesis in glioma.