Tomi Akinyemiju

<h4>Rationale</h4>Although lung cancer screening (LCS) with low-dose computed tomography (LDCT) is now recommended for those meeting standard risk factor-based eligibility criteria, the role of comorbidity in the uptake of LCS with LDCT in an older real-world U.S. population is not well established.<h4>Objective</h4>To examine the relationships between comorbidity, functional status and LCS utilization in the United States.<h4>Methods</h4>Using population-based data from the 2017-2019 Behavioral Risk Factor Surveillance System (BRFSS), we examined the association of comorbid conditions and functional limitations regarding activities of daily living with LCS utilization among participants that met the LCS criteria based on the US Preventive Service Taskforce guidelines. We employed multivariable weighted logistic regression models to evaluate these associations, both overall and within subgroups defined by age (<65 vs. ≥65 years), gender, and smoking history.<h4>Results</h4>Of 11,214 participants that met the eligibility criteria for LCS, 1731 (16%) underwent LCS with LDCT. The majority were white (90%), male (55%), former smokers (52%) and living with at least one chronic comorbid condition (77%). Over 28% had 3 or more comorbid conditions and approximately 40% of participants reported having some form of functional limitations. In the multivariable models, the likelihood of undergoing LCS with LDCT within the past year was positively associated with higher levels of comorbidity (≥5 vs. 0: aOR=2.34, 95% CI=1.22,4.48) but not with functional limitations (≥3 vs. 0: aOR=1.00, 95% CI=0.66, 1.50).<h4>Conclusion</h4>The presence of comorbid conditions is associated with a higher likelihood of undergoing LCS with LDCT. Because poor health status may diminish the benefits of screening, future research is needed to precisely characterize the health status of LCS-eligible individuals.

INTRODUCTION: Less than 40% of patients with ovarian cancer (OC) in the USA receive stage-appropriate guideline-adherent surgery and chemotherapy. Black patients with cancer report greater depression, pain and fatigue than white patients. Lack of access to healthcare likely contributes to low treatment rates and racial differences in outcomes. The Ovarian Cancer Epidemiology, Healthcare Access and Disparities study aims to characterise healthcare access (HCA) across five specific dimensions-Availability, Affordability, Accessibility, Accommodation and Acceptability-among black, Hispanic and white patients with OC, evaluate the impact of HCA on quality of treatment, supportive care and survival, and explore biological mechanisms that may contribute to OC disparities. METHODS AND ANALYSIS: We will use the Surveillance Epidemiology and Ends Results dataset linked with Medicare claims data from 9744 patients with OC ages 65 years and older. We will recruit 1641 patients with OC (413 black, 299 Hispanic and 929 white) from cancer registries in nine US states. We will examine HCA dimensions in relation to three main outcomes: (1) receipt of quality, guideline adherent initial treatment and supportive care, (2) quality of life based on patient-reported outcomes and (3) survival. We will obtain saliva and vaginal microbiome samples to examine prognostic biomarkers. We will use hierarchical regression models to estimate the impact of HCA dimensions across patient, neighbourhood, provider and hospital levels, with random effects to account for clustering. Multilevel structural equation models will estimate the total, direct and indirect effects of race on treatment mediated through HCA dimensions. ETHICS AND DISSEMINATION: Result dissemination will occur through presentations at national meetings and in collaboration with collaborators, community partners and colleagues across othercancer centres. We will disclose findings to key stakeholders, including scientists, providers and community members. This study has been approved by the Duke Institutional Review Board (Pro00101872). Safety considerations include protection of patient privacy. All disseminated data will be deidentified and summarised.

Forkhead box class O (FOXO) transcription factors play a pivotal role in regulating a variety of biological processes, including organismal development, cell signaling, cell metabolism, and tumorigenesis. Therefore, we hypothesize that genetic variants in FOXO pathway genes are associated with breast cancer (BC) risk. To test this hypothesis, we conducted a large meta-analysis using 14 published genome-wide association study (GWAS) data sets in the Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE) study. We assessed associations between 5214 (365 genotyped in DRIVE and 4849 imputed) common single-nucleotide polymorphisms (SNPs) in 55 FOXO pathway genes and BC risk. After multiple comparison corrections by the Bayesian false-discovery probability method, we found five SNPs to be significantly associated with BC risk. In stepwise multivariate logistic regression analysis with adjustment for age, principal components, and previously published SNPs in the same data set, three independent SNPs (i.e., FBXO32 rs10093411 A>G, FOXO6 rs61229336 C>T, and FBXO32 rs62521280 C>T) remained to be significantly associated with BC risk (p = 0.0008, 0.0011, and 0.0017, respectively). Additional expression quantitative trait loci analysis revealed that the FBXO32 rs62521280 T allele was associated with decreased messenger RNA (mRNA) expression levels in breast tissue, while the FOXO6 rs61229336 T allele was found to be associated with decreased mRNA expression levels in the whole blood cells. Once replicated by other investigators, these genetic variants may serve as new biomarkers for BC risk.

Background: Nigeria reports the highest age-standardized mortality rate for breast cancer (BC) among African countries and disproportionately high rates of high-grade cancer. Histological grade is a strong predictor of mortality, and evidence suggests that educational attainment influences cancer outcomes. Objective: We characterize the association between educational trends across the life-course and BC grade at diagnosis. Methods: Data on 224 BC patients enrolled in the Mechanisms for Established and Novel Risk Factors for Breast Cancer in Nigerian Women (MEND) study was analyzed. Participant and parental (mother and father) education was categorized as low (primary school or less) or high (secondary school or greater). Accordingly, the educational trend across the life-course was determined for each participant relative to each parent: stable high, increasing, decreasing, or stable low. BC grade was classified as high (grade 3) or low (grades 1-2). Findings: About 34% of participants, 71% of fathers, and 85% of mothers had low education. Approximately one-third of participants were diagnosed with high-grade BC. Participants with low-grade BC were more likely to have highly educated fathers (p = 0.04). After adjusting for age, comorbidities, marital status and mammogram screening, participants with highly educated fathers were 60% less likely to have high-grade BC (aOR 0.41; 95% CI 0.20 to 0.84) compared to those with less-educated fathers. Stable high life-course education relative to father was also associated with a significantly lower likelihood of having high-grade BC (aOR 0.36; 95% CI 0.15 to 0.87) compared to stable low life-course education. No significant associations were observed for the participant's education, mother's education, or life-course education relative to mother. Conclusions: Early-life socioeconomic status (SES) may influence BC grade. This deserves further study to inform policies that may be useful in reducing high-grade BC in Nigeria.

BACKGROUND: The association between obesity and breast cancer (BC) has been extensively studied among US, European and Asian study populations, with often conflicting evidence. However, despite the increasing prevalence of obesity and associated conditions in Africa, the continent with the highest age-standardized BC mortality rate globally, few studies have evaluated this association, and none has examined in relation to molecular subtypes among African women. The current analysis examines the association between body composition, defined by body mass index (BMI), height, and weight, and BC by molecular subtype among African women. METHODS: We estimated odds ratios (ORs) and 95% confidence intervals (95% CI) for the association between measures of body composition and BC and molecular subtypes among 419 histologically confirmed cases of BC and 286 healthy controls from the Mechanisms for Established and Novel Risk Factors for Breast Cancer in Women of Nigerian Descent (MEND) case-control study. RESULTS: Higher BMI (aOR: 0.79; 95% CI: 0.67, 0.95) and weight (aOR: 0.83; 95% CI: 0.69, 0.98) were associated with reduced odds of BC in adjusted models, while height was associated with non-statistically significant increased odds of BC (aOR: 1.07, 95% CI: 0.90, 1.28). In pre/peri-menopausal, but not post-menopausal women, both higher BMI and weight were significantly associated with reduced odds of BC. Further, higher BMI was associated with reduced odds of Luminal A, Luminal B, and HER2-enriched BC among pre/peri-menopausal women, and reduced odds of triple-negative BC among post-menopausal women. CONCLUSIONS: Higher BMI and weight were associated with reduced odds of BC overall and by molecular subtype among West African women. Larger studies of women of African descent are needed to definitively characterize these associations and inform cancer prevention strategies.