Impact of insomnia on ovarian cancer risk and survival: a Mendelian randomization study.

BACKGROUND: Insomnia is the most common sleep disorder in patients with epithelial ovarian cancer (EOC). We investigated the causal association between genetically predicted insomnia and EOC risk and survival through a two-sample Mendelian randomization (MR) study. METHODS: Insomnia was proxied using genetic variants identified in a genome-wide association study (GWAS) meta-analysis of UK Biobank and 23andMe. Using genetic associations with EOC risk and overall survival from the Ovarian Cancer Association Consortium (OCAC) GWAS in 66,450 women (over 11,000 cases with clinical follow-up), we performed Iterative Mendelian Randomization and Pleiotropy (IMRP) analysis followed by a set of sensitivity analyses. Genetic associations with survival and response to treatment in ovarian cancer study of The Cancer Genome Atlas (TCGA) were estimated controlling for chemotherapy and clinical factors. FINDINGS: Insomnia was associated with higher risk of endometrioid EOC (OR = 1.60, 95% CI 1.05-2.45) and lower risk of high-grade serous EOC (HGSOC) and clear cell EOC (OR = 0.79 and 0.48, 95% CI 0.63-1.00 and 0.27-0.86, respectively). In survival analysis, insomnia was associated with shorter survival of invasive EOC (OR = 1.45, 95% CI 1.13-1.87) and HGSOC (OR = 1.4, 95% CI 1.04-1.89), which was attenuated after adjustment for body mass index and reproductive age. Insomnia was associated with reduced survival in TCGA HGSOC cases who received standard chemotherapy (OR = 2.48, 95% CI 1.13-5.42), but was attenuated after adjustment for clinical factors. INTERPRETATION: This study supports the impact of insomnia on EOC risk and survival, suggesting treatments targeting insomnia could be pivotal for prevention and improving patient survival. FUNDING: National Institutes of Health, National Cancer Institute. Full funding details are provided in acknowledgments.

Racial and Ethnic Inequities in Cancer Care Continuity During the COVID-19 Pandemic Among Those With SARS-CoV-2.

Importance: Racially and ethnically minoritized US adults were disproportionately impacted by the COVID-19 pandemic and experience poorer cancer outcomes, including inequities in cancer treatment delivery. Objective: To evaluate racial and ethnic disparities in cancer treatment delays and discontinuations (TDDs) among patients with cancer and SARS-CoV-2 during different waves of the COVID-19 pandemic in the United States. Design, Setting, and Participants: This cross-sectional study used data from the American Society of Clinical Oncology Survey on COVID-19 in Oncology Registry (data collected from April 2020 to September 2022), including patients with cancer also diagnosed with SARS-CoV-2 during their care at 69 US practices. Racial and ethnic differences were examined during 5 different waves of the COVID-19 pandemic in the United States based on case surge (before July 2020, July to November 2020, December 2020 to March 2021, April 2021 to February 2022, and March to September 2022). Exposures: Race and ethnicity. Main Outcomes and Measures: TDD was defined as any cancer treatment postponed more than 2 weeks or cancelled with no plans to reschedule. To evaluate TDD associations with race and ethnicity, adjusted prevalence ratios (aPRs) were estimated using multivariable Poisson regression, accounting for nonindependence of patients within clinics, adjusting for age, sex, body mass index, comorbidities, cancer type, cancer extent, and SARS-CoV-2 severity (severe defined as death, hospitalization, intensive care unit admission, or mechanical ventilation). Results: A total of 4054 patients with cancer and SARS-CoV-2 were included (143 [3.5%] American Indian or Alaska Native, 176 [4.3%] Asian, 517 [12.8%] Black or African American, 469 [11.6%] Hispanic or Latinx, and 2747 [67.8%] White; 2403 [59.3%] female; 1419 [35.1%] aged 50-64 years; 1928 [47.7%] aged ≥65 years). The analysis focused on patients scheduled (at SARS-CoV-2 diagnosis) to receive drug-based therapy (3682 [90.8%]), radiation therapy (382 [9.4%]), surgery (218 [5.4%]), or transplant (30 [0.7%]), of whom 1853 (45.7%) experienced TDD. Throughout the pandemic, differences in racial and ethnic inequities based on case surge with overall TDD decreased over time. In multivariable analyses, non-Hispanic Black (third wave: aPR, 1.56; 95% CI, 1.31-1.85) and Hispanic or Latinx (third wave: aPR, 1.35; 95% CI, 1.13-1.62) patients with cancer were more likely to experience TDD compared with non-Hispanic White patients during the first year of the pandemic. By 2022, non-Hispanic Asian patients (aPR, 1.51; 95% CI, 1.08-2.12) were more likely to experience TDD compared with non-Hispanic White patients, and non-Hispanic American Indian or Alaska Native patients were less likely (aPR, 0.37; 95% CI, 0.16-0.89). Conclusions and Relevance: In this cross-sectional study of patients with cancer and SARS-CoV-2, racial and ethnic inequities existed in TDD throughout the pandemic; however, the disproportionate burden among racially and ethnically minoritized patients with cancer varied across SARS-CoV-2 waves. These inequities may lead to downstream adverse impacts on cancer mortality among minoritized adults in the United States.

Characteristics of Patients With Cancer and COVID-19 Who Discontinued Cancer Treatment.

This cross-sectional study evaluates the prevalence of and characteristics associated with discontinuation of cancer treatment among patients who received a diagnosis of COVID-19 during their treatment planning.

Recreational physical activity and breast cancer risk by menopausal status and tumor hormone receptor status: results from the Nurses' Health Studies.

PURPOSE: Physical activity is associated with lower breast cancer risk, especially in postmenopausal women. Associations in premenopausal women are less well established. METHODS: We evaluated recreational physical activity and breast cancer risk in the Nurses' Health Study (NHS) and NHSII (187,278 women; n = 12,785 breast cancers; follow-up: NHS = 1986-2016, NHSII = 1989-2017) by menopausal status and estrogen (ER) and progesterone (PR) receptor status. Physical activity was evaluated as updated cumulative average of metabolic equivalent of task (MET)-h/week. Cox proportional hazards models were used to estimate multivariable hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: Recreational physical activity was inversely associated with breast cancer risk in pre- and postmenopausal women. Higher activity levels were associated with lower risk of ER+/PR + breast cancer in both pre- and postmenopausal women (e.g., total recreational activity, ≥ 27 vs < 3 MET-h/week, premenopausal HR = 0.83, 95%CI = (0.70-0.99), postmenopausal HR = 0.86 (0.78-0.95); pheterogeneity = 0.97). Results were attenuated with adjustment for current body mass index (BMI) among postmenopausal, but not premenopausal, women (e.g., ≥ 27 vs < 3 MET-h/week, premenopausal HR = 0.83 (0.69-0.98); postmenopausal HR = 0.95 (0.85-1.05); pheterogeneity = 0.99). In analyses of moderate-vigorous activity and breast cancer risk, no heterogeneity by menopausal status was observed (phet ≥ 0.53; e.g., ≥ 27 vs < 3 MET-h/week, ER+/PR+, premenopausal HR = 0.88 (0.69-1.11); postmenopausal HR = 0.71 (0.58-0.88). No associations were observed for ER-/PR- disease. CONCLUSIONS: Recreational physical activity was associated with lower breast cancer risk in both pre- and postmenopausal women, supporting recreational physical activity as an accessible, modifiable exposure associated with reduced breast cancer risk regardless of menopausal status.

Impact of COVID-19-related experiences on health-related quality of life in cancer survivors in the United States.

OBJECTIVE: Little evidence exists on the impact of the COVID-19 pandemic on cancer survivors, limiting recommendations to improve health-related quality of life (HRQoL) in this population. We describe survivors' pandemic experiences and examine associations between COVID-19-related exposures, psychosocial experiences, and HRQoL. METHODS: Between May 2020-April 2021, survivors completed cross-sectional questionnaires capturing COVID-19-related exposures (e.g., exposure to virus, job loss); psychosocial experiences (i.e., COVID-19-related anxiety/depression, disruptions to health care and daily activities/social interactions, satisfaction with providers' response to COVID, financial hardship, perceived benefits of the pandemic, social support, and perceived stress management ability); and HRQoL. RESULTS: Data were collected from N = 11,325 survivors in the United States. Participants were mostly female (58%), White (89%) and non-Hispanic (88%), and age 63 on average. Breast cancer was the most common diagnosis (23%). Eight percent of participants reported being exposed to COVID-19; 1% tested positive. About 6% of participants lost their jobs, while 24% lost household income. Nearly 30% avoided attending in-person oncology appointments because of the pandemic. Poorer HRQoL was associated with demographic (younger age; female; non-Hispanic White), clinical (Medicare; stage IV disease; hematologic/digestive/respiratory system cancer), and psychosocial factors (low perceived benefits and stress management ability; more disruption to health care and daily activities/social interactions; financial hardship). CONCLUSIONS: COVID-19-related stressors were associated with various psychosocial experiences in cancer survivors, and these psychosocial experiences were associated with HRQoL above and beyond demographic and clinical factors.

Barriers to endocrine therapy adherence: perspectives of Black breast cancer survivors and their providers.

PURPOSE: Adherence to oral endocrine therapy (ET) remains an issue for up to half of women prescribed these medications. There is emerging data that Black breast cancer survivors (BCS) have lower rates of ET adherence. Given the disparities in breast cancer recurrence and survival for Black BCS compared to their White counterparts, the goal of this study is to better understand barriers to ET adherence among Black BCS from the patient and provider perspectives. METHODS: In this qualitative study, we conducted semi-structured interviews between October 29, 2021, and March 1, 2023. Interviews were recorded and transcribed, and coded data were organized into primary and secondary themes. Participants were recruited from a single academic cancer center. A convenience sample of 24 Black BCS and 9 medical oncology providers was included. Eligible BCS were 18 years or older, English-speaking, diagnosed with stage I-III hormone receptor-positive breast cancer, who had initiated ET. RESULTS: Mean age of the BCS was 55 years (interquartile range, IQR 17 years). About one-fourth had a high school diploma or less (26.1%) and 47% completed a college education or higher. Approximately one-third of participants had annual household incomes of $40,000 or less (30.4%) or more than $100,000 (30.4%). Forty-three percent of the patient participants had private insurance; 11% were insured through Medicaid or the federal healthcare exchange; 26.1% had Medicare; and 13% were uninsured. Of the 9 medical oncology providers interviewed, 2 were advanced practice providers, and 7 were medical oncologists. We found 3 major themes: (1) Black BCS often had concerns about ET before initiation; (2) after initiation, both BCS and providers reported side effects as the most impactful barrier to ET adherence; and (3) survivors experienced challenges with managing ET side effects. CONCLUSIONS: Our results suggest that multifaceted support interventions for managing ET-related symptoms may lead to improved adherence to ET among Black women and may reduce disparities in outcomes. IMPLICATIONS FOR CANCER SURVIVORS: Multifaceted support interventions for managing ET-related symptoms may lead to improved adherence to ET among Black breast cancer survivors.

Impact of Pre-Diagnostic Risk Factors on Short- and Long-Term Ovarian Cancer Survival Trajectories: A Longitudinal Observational Study.

Tumor- and treatment-related factors are established predictors of ovarian cancer survival. New studies suggest a differential impact of exposures on ovarian cancer survival trajectories (i.e., rapidly fatal to long-term disease). This study examined the impact of pre-diagnostic risk factors on short- and long-term ovarian cancer survival trajectories in the Canadian context. This population-based longitudinal observational study included women diagnosed with invasive epithelial ovarian cancer from 1995 to 2004 in Ontario. Data were obtained from medical records, interviews, and the provincial cancer registry. Extended Cox proportional hazard models estimated the association between risk factors and all-cause and ovarian cancer-specific mortality by survival time intervals (<3 years (i.e., short-term survival), 3 to <6 years, 6 to <10 years, and ≥10 years (i.e., long-term survival)). Among 1421 women, histology, stage, and residual disease were the most important predictors of all-cause mortality in all survival trajectories, particularly for short-term survival. Reproductive and lifestyle factors did not strongly impact short-term overall survival but were associated with long-term overall survival. As such, among long-term survivors, history of breastfeeding significantly decreased the risk of all-cause mortality (HR 0.65; 95% CI 0.46, 0.93; p < 0.05), whereas smoking history (HR 1.75; 95% CI 1.27, 2.40; p < 0.05) and obesity (HR 1.81; 95% CI 1.24, 2.65; p < 0.05) significantly increased the risk of all-cause mortality. The findings were consistent with ovarian cancer-specific mortality. These findings suggest that pre-diagnostic exposures differentially influence survival time following a diagnosis of ovarian cancer.

Lifetime Exposure to Cigarette Smoke, B-Cell Tumor Immune Infiltration, and Immunoglobulin Abundance in Ovarian Tumors.

BACKGROUND: Cigarette smoke exposure has been linked to systemic immune dysfunction, including for B-cell and immunoglobulin (Ig) production, and poor outcomes in patients with ovarian cancer. No study has evaluated the impact of smoke exposure across the life-course on B-cell infiltration and Ig abundance in ovarian tumors. METHODS: We measured markers of B and plasma cells and Ig isotypes using multiplex immunofluorescence on 395 ovarian cancer tumors in the Nurses' Health Study (NHS)/NHSII. We conducted beta-binomial analyses evaluating odds ratios (OR) and 95% confidence intervals (CI) for positivity of immune markers by cigarette exposure among cases and Cox proportional hazards models to evaluate hazard ratios (HR) and 95% CI for developing tumors with low (

Risk factors and health behaviors associated with loneliness among cancer survivors during the COVID-19 pandemic.

Loneliness may exacerbate poor health outcomes particularly among cancer survivors during the COVID-19 pandemic. Little is known about the risk factors of loneliness among cancer survivors. We evaluated the risk factors of loneliness in the context of COVID-19 pandemic-related prevention behaviors and lifestyle/psychosocial factors among cancer survivors. Cancer survivors (n = 1471) seen at Huntsman Cancer Institute completed a survey between August-September 2020 evaluating health behaviors, medical care, and psychosocial factors including loneliness during COVID-19 pandemic. Participants were classified into two groups: 'lonely' (sometimes, usually, or always felt lonely in past month) and 'non-lonely' (never or rarely felt lonely in past month). 33% of cancer survivors reported feeling lonely in the past month. Multivariable logistic regression showed female sex, not living with a spouse/partner, poor health status, COVID-19 pandemic-associated lifestyle factors including increased alcohol consumption and marijuana/CBD oil use, and psychosocial stressors such as disruptions in daily life, less social interaction, and higher perceived stress and financial stress were associated with feeling lonely as compared to being non-lonely (all p < 0.05). A significant proportion of participants reported loneliness, which is a serious health risk among vulnerable populations, particularly cancer survivors. Modifiable risk factors such as unhealthy lifestyle behaviors and psychosocial stress were associated with loneliness. These results highlight the need to screen for unhealthy lifestyle factors and psychosocial stressors to identify cancer survivors at increased risk of loneliness and to develop effective management strategies.

Fulfilled Mind, Healthy Gut? Relationships of Eudaimonic Psychological Well-Being With the Gut Microbiome in Postmenopausal Women.

OBJECTIVE: Eudaimonic facets of psychological well-being (PWB), like purpose in life and sense of mastery, are associated with healthy aging. Variation in the gut microbiome may be one pathway by which mental health influences age-related health outcomes. However, associations between eudaimonic PWB and the gut microbiome are understudied. We examined whether purpose in life and sense of mastery, separately, were associated with features of the gut microbiome in older women. METHODS: Participants were from the Mind-Body Study ( N = 206, mean age = 61 years), a substudy of the Nurses' Health Study II cohort. In 2013, participants completed the Life Engagement Test and the Pearlin Mastery Scale. Three months later, up to two pairs of stool samples were collected, 6 months apart. Covariates included sociodemographics, depression, health status, and health behaviors. Analyses examined associations of PWB with gut microbiome taxonomic diversity, overall community structure, and specific species/pathways. To account for multiple testing, statistical significance was established using Benjamini-Hochberg adjusted p values (i.e., q values ≤0.25). RESULTS: We found no evidence of an association between PWB and gut microbiome alpha diversity. In multivariate analysis, higher purpose levels were significantly associated with lower abundance of species previously linked with poorer health outcomes, notably Blautia hydrogenotrophica and Eubacterium ventriosum ( q values ≤0.25). No significant associations were found between PWB and metabolic pathways. CONCLUSIONS: These findings offer early evidence suggesting that eudaimonic PWB is linked with variation in the gut microbiome, and this might be one pathway by which PWB promotes healthy aging.

Inequities in the Impacts of Hurricanes and Other Extreme Weather Events for Cancer Survivors.

In this minireview, we examine the impacts of hurricanes and other extreme weather events on cancer survivors, focusing on structural and social determinants of health. We briefly explore influences on biological, psychosocial, and behavioral outcomes and discuss risk and resilience factors in cancer survivorship during and after hurricanes. Our goal is to inform future directions for research that can identify areas in which we can most efficiently improve cancer outcomes and inform changes in health systems, clinical practice, and public health policies. This timely minireview provides researchers and clinicians with an overview of challenges and opportunities for improving disaster preparedness and response for cancer survivors.

WITHDRAWN: Impact of spatial clustering of cytotoxic and tumor infiltrating lymphocytes on overall survival in women with high grade serous ovarian cancer.

The authors have withdrawn their manuscript owing to incorrect handling of multiple measures in the survival analyses. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.

Breast density analysis of digital breast tomosynthesis.

Mammography shifted to digital breast tomosynthesis (DBT) in the US. An automated percentage of breast density (PD) technique designed for two-dimensional (2D) applications was evaluated with DBT using several breast cancer risk prediction measures: normalized-volumetric; dense volume; applied to the volume slices and averaged (slice-mean); and applied to synthetic 2D images. Volumetric measures were derived theoretically. PD was modeled as a function of compressed breast thickness (CBT). The mean and standard deviation of the pixel values were investigated. A matched case-control (CC) study (n = 426 pairs) was evaluated. Odd ratios (ORs) were estimated with 95% confidence intervals. ORs were significant for PD: identical for volumetric and slice-mean measures [OR = 1.43 (1.18, 1.72)] and [OR = 1.44 (1.18, 1.75)] for synthetic images. A 2nd degree polynomial (concave-down) was used to model PD as a function of CBT: location of the maximum PD value was similar across CCs, occurring at 0.41 × CBT, and PD was significant [OR = 1.47 (1.21, 1.78)]. The means from the volume and synthetic images were also significant [ORs ~ 1.31 (1.09, 1.57)]. An alternative standardized 2D synthetic image was constructed, where each pixel value represents the percentage of breast density above its location. Several measures were significant and an alternative method for constructing a standardized 2D synthetic image was produced.

Associations between prediagnostic aspirin use and ovarian tumor gene expression.

BACKGROUND: Aspirin use has been associated with reduced ovarian cancer risk, yet the underlying biological mechanisms are not fully understood. To gain mechanistic insights, we assessed the association between prediagnosis low and regular-dose aspirin use and gene expression profiles in ovarian tumors. METHODS: RNA sequencing was performed on high-grade serous, poorly differentiated, and high-grade endometrioid ovarian cancer tumors from the Nurses' Health Study (NHS), NHSII, and New England Case-Control Study (n = 92 cases for low, 153 cases for regular-dose aspirin). Linear regression identified differentially expressed genes associated with aspirin use, adjusted for birth decade and cohort. False discovery rates (FDR) were used to account for multiple testing and gene set enrichment analysis was used to identify biological pathways. RESULTS: No individual genes were significantly differentially expressed in ovarian tumors in low or regular-dose aspirin users accounting for multiple comparisons. However, current versus never use of low-dose aspirin was associated with upregulation of immune pathways (e.g., allograft rejection, FDR = 5.8 × 10-10 ; interferon-gamma response, FDR = 2.0 × 10-4 ) and downregulation of estrogen response pathways (e.g., estrogen response late, FDR = 4.9 × 10-8 ). Ovarian tumors from current regular aspirin users versus never users were also associated with upregulation in interferon pathways (FDR <1.5 × 10-4 ) and downregulation of multiple extracellular matrix (ECM) architecture pathways (e.g., ECM organization, 4.7 × 10-8 ). CONCLUSION: Our results suggest low and regular-dose aspirin may impair ovarian tumorigenesis in part via enhancing adaptive immune response and decreasing metastatic potential supporting the likely differential effects on ovarian carcinogenesis and progression by dose of aspirin.

Relationships among Inflammatory Biomarkers and Objectively Assessed Physical Activity and Sleep during and after Chemotherapy for Gynecologic Malignancies.

Little is known regarding associations between inflammatory biomarkers and objectively measured physical activity and sleep during and after chemotherapy for gynecologic cancer; thus, we conducted a longitudinal study to address this gap. Women with gynecologic cancer (patients) and non-cancer controls (controls) completed assessments before chemotherapy cycles 1, 3, and 6 (controls assessed contemporaneously), as well as at 6- and 12-month follow-ups. Physical activity and sleep were measured using wrist-worn actigraphs and sleep diaries, and blood was drawn to quantify circulating levels of inflammatory markers. Linear and quadratic random-effects mixed models and random-effects fluctuation mixed models were used to examine physical activity and sleep over time, as well as the associations with inflammatory biomarkers. On average, patients (n = 97) and controls (n = 104) were 62 and 58 years old, respectively. Compared to controls, patients were less active, more sedentary, had more time awake after sleep onset, and had lower sleep efficiency (p-values < 0.05). Across groups, higher levels of TNF-α were associated with more sedentary time and less efficient sleep (p-values ≤ 0.05). Higher levels of IL-1ß, TNF-α, and IL-6 were associated with lower levels of light physical activity (p-values < 0.05). Associations between inflammatory biomarkers, physical activity, and sleep did not differ between patients and controls. Given these results, we speculate that inflammation may contribute to less physical activity and more sleep problems that persist even 12 months after completing chemotherapy.

The relationship of lifetime history of depression on the ovarian tumor immune microenvironment.

BACKGROUND: Depression is associated with a higher ovarian cancer risk. Prior work suggests that depression can lead to systemic immune suppression, which could potentially alter the anti-tumor immune response. METHODS: We evaluated the association of pre-diagnosis depression with features of the anti-tumor immune response, including T and B cells and immunoglobulins, among women with ovarian tumor tissue collected in three studies, the Nurses' Health Study (NHS; n = 237), NHSII (n = 137) and New England Case-Control Study (NECC; n = 215). Women reporting depressive symptoms above a clinically relevant cut-point, antidepressant use, or physician diagnosis of depression at any time prior to diagnosis of ovarian cancer were considered to have pre-diagnosis depression. Multiplex immunofluorescence was performed on tumor tissue microarrays to measure immune cell infiltration. In pooled analyses, we estimated odds ratios (OR) and 95% confidence intervals (CI) for the positivity of tumor immune cells using a beta-binomial model comparing those with and without depression. We used Bonferroni corrections to adjust for multiple comparisons. RESULTS: We observed no statistically significant association between depression status and any immune markers at the Bonferroni corrected p-value of 0.0045; however, several immune markers were significant at a nominal p-value of 0.05. Specifically, there were increased odds of having recently activated cytotoxic (CD3+CD8+CD69+) and exhausted-like T cells (CD3+Lag3+) in tumors of women with vs. without depression (OR = 1.36, 95 %CI = 1.09-1.69 and OR = 1.24, 95 %CI = 1.01-1.53, respectively). Associations were comparable when considering high grade serous tumors only (comparable ORs = 1.33, 95 %CI = 1.05-1.69 and OR = 1.25, 95 %CI = 0.99-1.58, respectively). There were decreased odds of having tumor infiltrating plasma cells (CD138+) in women with vs. without depression (OR = 0.54, 95 %CI = 0.33-0.90), which was similar among high grade serous carcinomas, although not statistically significant. Depression was also related to decreased odds of having naïve and memory B cells (CD20+: OR = 0.54, 95 %CI = 0.30-0.98) and increased odds of IgG (OR = 1.22, 95 %CI = 0.97-1.53) in high grade serous carcinomas. CONCLUSION: Our results provide suggestive evidence that depression may influence ovarian cancer outcomes through changes in the tumor immune microenvironment, including increasing T cell activation and exhaustion and reducing antibody-producing B cells. Further studies with clinical measures of depression and larger samples are needed to confirm these results.

The Association of Kidney Function and Inflammatory Biomarkers with Epithelial Ovarian Cancer Risk.

BACKGROUND: One of the mechanisms of ovarian tumorigenesis is through inflammation. Kidney dysfunction is associated with increased inflammation; thus, we assessed its relationship with ovarian cancer risk. METHODS: In prospectively collected samples, we evaluated the association of kidney function markers and C-reactive protein (CRP) with ovarian cancer risk in the UK Biobank. We used multivariable-adjusted Cox proportional hazards models to evaluate quartiles of serum and urine markers with ovarian cancer risk overall and by histology. We assessed effect modification by CRP (≤3.0, >3.0 mg/L). RESULTS: Among 232,908 women (1,110 ovarian cancer cases diagnosed from 2006-2020), we observed no association between estimated glomerular filtration rate and ovarian cancer risk (Q4 vs. Q1: HR, 1.00; 95% confidence intervals, 0.83-1.22). Potassium was associated with endometrioid (Q4 vs. Q1: 0.33, 0.11-0.98) and clear cell (4.74, 1.39-16.16) tumors. Poor kidney function was associated with a nonsignificant increase in ovarian cancer risk among women with CRP>3.0 mg/L (e.g., uric acid Q4 vs. Q1; 1.23, 0.81-1.86), but not CRP≤3.0 mg/L (0.83, 0.66-1.05). Other associations did not vary across CRP categories. CONCLUSIONS: Kidney function was not clearly associated with ovarian cancer risk. Larger studies are needed to evaluate possible histology specific associations. Given the suggestive trend for increased ovarian cancer risk in women with poor kidney function and high CRP, future work is needed, particularly in populations with a high prevalence of inflammatory conditions. IMPACT: This study provided the first evaluation of markers of kidney function in relation to ovarian cancer risk.

Relationships among Inflammatory Biomarkers and Self-Reported Treatment-Related Symptoms in Patients Treated with Chemotherapy for Gynecologic Cancer: A Controlled Comparison.

Previous research suggests that inflammation triggers cancer-treatment-related symptoms (i.e., fatigue, depression, and disruptions in sleep and physical activity), but evidence is mixed. This study examined relationships between inflammatory biomarkers and symptoms in patients with gynecologic cancer compared to age-matched women with no cancer history (i.e., controls). Patients (n = 121) completed assessments before chemotherapy cycles 1, 3, and 6, and 6 and 12 months later. Controls (n = 105) completed assessments at similar timepoints. Changes in inflammation and symptomatology were evaluated using random-effects mixed models, and cross-sectional differences between patients and controls in inflammatory biomarkers and symptoms were evaluated using least squares means. Associations among inflammatory biomarkers and symptoms were evaluated using random-effects fluctuation mixed models. The results indicated that compared to controls, patients typically have higher inflammatory biomarkers (i.e., TNF-alpha, TNFR1, TNFR2, CRP, IL-1ra) and worse fatigue, depression, and sleep (ps < 0.05). Patients reported lower levels of baseline physical activity (p = 0.02) that became more similar to controls over time. Significant associations were observed between CRP, depression, and physical activity (ps < 0.05), but not between inflammation and other symptoms. The results suggest that inflammation may not play a significant role in fatigue or sleep disturbance among gynecologic cancer patients but may contribute to depression and physical inactivity.