Cancer Incidence Research Articles

High percentage of cancers potentially preventable: Better strategies, such as education, policy, and community-level interventions, are needed to reduce modifiable risk factors associated with cancer incidence and death.

High percentage of cancers potentially preventable: Better strategies, such as education, policy, and community-level interventions, are needed to reduce modifiable risk factors associated with cancer incidence and death.

Interaction of base excision repair gene polymorphism and estrogen-DNA adducts in breast cancer risk among East Asian women.

In East Asia, the incidence of breast cancer has been increasing rapidly, particularly among premenopausal women. An elevated ratio of estrogen-DNA adducts was linked to a higher risk of breast cancer. The present study explored the influence of the interaction between base excision repair (BER) gene polymorphisms and estrogen-DNA adducts on breast cancer risk. We conducted a case-control study comprising healthy volunteers and individuals with benign breast disease (control arm, n = 176) and patients with invasive carcinoma or carcinoma in situ (case arm, n = 177). Genotyping for BER-related genes, including SMUG1, OGG1, ERCC5, and APEX1, was performed. A logistic regression model, incorporating interactions between gene polymorphisms, estrogen-DNA adduct ratio, and clinical variables, was used to identify the risk factors for breast cancer. Univariate analysis indicated marginal associations between breast cancer risk and APEX1 rs1130409 T > G (P = 0.057) and APEX1 rs1760944 T > G (P = 0.065). Multivariate regression analysis revealed significant associations with increased breast cancer risk for APEX1_rs1130409 (GT/GG versus TT) combined with a natural logarithmic value of the estrogen-DNA adduct ratio (estimated OR 1.164, P = 0.023) and premenopausal status with an estrogen-DNA adduct ratio > 2.93 (estimated OR 2.433, P = 0.001). APEX1_rs1130409 (GT/GG versus TT) polymorphisms, which are related to decreased BER activity, combined with an increased ratio of estrogen-DNA adducts, increase the risk of breast cancer in East Asian women.

Discrepancies between clinical trial availability and the incidence of gynecologic cancers

Discrepancies between clinical trial availability and the incidence of gynecologic cancers

The escalating incidence of advanced-stage cervical cancer among underrepresented patients in the United States

The escalating incidence of advanced-stage cervical cancer among underrepresented patients in the United States

Prostate-Specific Antigen Stratification for Predicting Advanced Prostate Cancer Events in Men Approaching Age Limits for Recommended Screening.

Our goal was to quantify the ability of various PSA values in predicting the likelihood of developing metastatic or fatal prostate cancer in older men. We used a random sample of patients in the US Veterans Health Administration to identify 80,706 men who had received PSA testing between ages 70 to 75. Our primary end point was time to development of either metastatic prostate cancer or death from prostate cancer. We used cumulative/dynamic modeling to account for competing events (death from non-prostate cancer causes) in studying both the discriminative ability of PSA as well as for positive predictive value and negative predictive value at 3 time points. PSA demonstrated time-dependent predictive discrimination, with receiver operating characteristic area under the curve at 5, 10, and 14 years decreasing from 0.83 to 0.77 to 0.73, respectively, but without statistically significant difference when stratified by race. At PSA thresholds between 1 and 8 ng/mL, the positive predictive value of developing advanced prostate cancer was significantly greater in Black than White patients. For instance, at a PSA > 3, at 5, 10, and 14 years, White patients had 2.4%, 2.9%, and 3.7% risk of an event, whereas Black patients had 4.3%, 6.5%, and 8.3% risk. In men aged 70 to 75 deciding whether to cease PSA testing with borderline-elevated PSA values, the risk of developing metastatic or fatal prostate cancer is quantifiable and relatively low. Risk assessment in this setting must account for the higher incidence of prostate cancer in Black men.

Skin cancer incidence in Mexican renal transplant recipients: a cohort over 56 years.

Skin cancer is a primary health concern in renal transplant recipients (RTRs). Existing research mainly stems from North America, Europe, and Australia, with limited data from Latin America. This 56-year (1967-2023) retrospective cohort study explores skin cancer incidence in Mexican RTRs. Our objective was to assess the long-term incidence of malignant cutaneous neoplasms in Mexican RTRs. Over 56 years, 1642 RTRs (58% male) were studied. Median follow-up was 8.4 years; median age at transplantation was 32.6 years. Skin cancer incidence was 6.6% (95% CI: 5.5-7.9), with an incidence density rate of 6.5 (95% CI: 5.4-7.9) per 1000 person-years and a median latency of 9.8 years. Incidence increased with longer transplantation-related immunosuppression (TRI), with a relative risk for >30 years of TRI of 4.8 (95% CI: 2.6-9.1) for any skin cancer and 7.5 (95% CI: 3.8-14.6) for squamous cell carcinoma (SCC). SCC was the most common malignancy (76.1%), followed by basal cell carcinomas (BCC), with a 3.6:1 ratio. Metastatic SCC occurred in 6.5% of skin cancer patients, with a skin cancer-related mortality rate of 2.7%. Limitations of the study include its single-center and retrospective design and unassessed factors such as human papillomavirus infection and sun exposure. Our study provides unique insights into the epidemiology of skin cancer among Mexican RTRs. It constitutes the largest cohort of skin cancer cases among RTRs in Mexico and, to our knowledge, in Latin America. Despite the lack of recognition of a high skin cancer incidence in non-White RTRs, our 6.6% incidence underscores the need to enhance surveillance programs.

Silibinin Induces Both Apoptosis and Necroptosis with Potential Anti-tumor Efficacy in Lung Cancer.

Lung cancer incidence is steadily on the rise, posing a growing threat to human health. The search for therapeutic drugs from natural active substance and elucidating their mechanism have been the focus of anti-tumor research. In our work, Silibinin (SiL) was chosen as a possible substance that could inhibit lung cancer. and its effects on inducing tumor cell death have been studied. CCK-8 analysis and morphological observation were used to assess the cytotoxic impacts of SiL on lung cancer cells in vitro. The alterations in mitochondrial membrane potential (MMP) and apoptosis rate of cells were detected by flow cytometry. The level of lactate dehydrogenase (LDH) release out of cells was measured. The expression changes of apoptosis or necroptosis-related proteins were detected using western blotting. Protein interactions among RIPK1, RIPK3 and MLKL were analyzed using the co-immunoprecipitation technique. In vivo, SiL was evaluated for its antitumor effects using LLC tumor-bearing mice with mouse lung cancer. With an increased dose of SiL, the proliferation ability of A549 cells was considerably inhibited, and the accompanying cell morphology changed. The results of flow cytometry showed that after SiL treatment, MMP levels decreased, and the proportion of cells undergoing apoptosis increased. The proteins associated with apoptosis were upregulated and activated. The amount of LDH released from the cells increased following SiL treatment, accompanied by augmented expression and phosphorylation levels of necroptosis-related proteins. The co-IP assay further confirmed necrosome formation induced by SiL. Furthermore, Necrosulfonamide (an MLKL inhibitor) increased the apoptotic rate of SiL-treated cells and aggravated the cytotoxic effect of SiL, indicating that necroptosis blockade could switch cell death to apoptosis and increase the inhibitory effect of SiL on A549 cells. In LLC-bearing mice, gastric administration of SiL significantly inhibited tumor growth. This study helped clarify the anti-tumor mechanism of SiL against lung cancer, elucidating its role in dual induction of apoptosis and necroptosis. In particular, necroptosis blockade could switch cell death to apoptosis and increase the inhibitory effect of SiL. Our work provided an experimental basis for the research on cell death induced by SiL and revealed its possible applications for improving the management of lung cancer.</p>.

Blood microRNA testing in participants with suspicious low-dose CT findings: follow-up of the BioMILD lung cancer screening trial

The proper management of suspicious radiologic findings is crucial to optimize the effectiveness of low-dose computed tomography (LDCT) lung cancer screening trials. In the BioMILD study, we evaluated the utility of combining a plasma 24-microRNA signature classifier (MSC) and LDCT to define the individual risk and personalize screening strategies. Here we aim to assess the utility of repeated MSC testing during annual screening rounds in 1024 participants with suspicious LDCT findings. The primary outcome was two-year lung cancer incidence in relation to MSC test results, reported as relative risk (RR) with 95% confidence interval (CI). Lung cancer incidence and mortality were estimated using extended Cox models for time-dependent covariates, yielding the respective hazard ratios (HR). Clinicaltrials.gov ID: NCT02247453. With a median follow-up of 8.5 years, the full study set included 1403 indeterminate LDCT (CTind) and 584 positive LDCT (CT+) results. A lung cancer RR increase in MSC+compared to MSC- participants was observed in both the CTind (RR: 2.5; 95% CI: 1.4-4.32) and CT+ (RR: 2.6; 95% CI: 1.81-3.74) groups and was maintained when considering stage I or resectable tumors only. A 98% negative predictive value in CTind/MSC- and a 30% positive predictive value in CT+/MSC+ lesions were recorded. At seven years' follow-up, MSC+ participants had a cumulative HR of 4.4 (95% CI: 3.0-6.4) for lung cancer incidence and of 8.1 (95% CI: 2.7-24.5) for lung cancer mortality. Our study shows that MSC can be reliably performed during LDCT screening rounds to increase the accuracy of lung cancer risk and mortality prediction and supports its clinical utility in the management of LDCT findings of uncertain malignancy. Italian Association for Cancer Research; Italian Ministry of Health; Horizon2020; National Cancer Institute (NCI); Gensignia LifeScience.

Increase in uterine cancer incidence among Black patients in the United States: A United States Cancer Statistics Study of nearly 95,000 patients from 2001 to 2019

Increase in uterine cancer incidence among Black patients in the United States: A United States Cancer Statistics Study of nearly 95,000 patients from 2001 to 2019

SEOM-GETNE-TTCC Clinical guideline thyroid cancer (2023).

Thyroid cancer (TC) represents 3% of global cancer incidence. Recent changes have optimized treatment decisions based on risk assessment, molecular profiling, and imaging assessment, leading the development of targeted agents that have modified the natural history of this disease. This increasing complexity on treatment options requires careful assessment at the different stages of the disease to provide the most suitable approach from diagnosis to long-term follow-up. This guideline aims to offer a comprehensive and practical overview on the current status and last updates of TC management.

A more accurate measure of endometrial cancer incidence rates in New Mexico: A hysterectomy-corrected analysis

A more accurate measure of endometrial cancer incidence rates in New Mexico: A hysterectomy-corrected analysis

The Role of Multiple Mediation with Contextual Neighborhood Measures in Ovarian Cancer Survival..

BackgroundMediation by multiple agents can affect the relation between neighborhood deprivation and segregation indices and ovarian cancer survival. In this paper, we examine a variety of potential clinical mediators in the association between deprivation indices (DIs) and segregation indices (SIs) with all-cause survival among women with ovarian cancer in the African American Cancer Epidemiology Study (AACES). MethodsWe use novel Bayesian multiple mediation structural models to assess the joint role of mediators (stage at diagnosis, histology, diagnostic delay) combined with the DIs and SIs (Yost, ADI, Kolak’s URB, ICE-income) and a set of confounders with survival. The confounder set is selected in a preliminary step, and each DI or SI is included in separate model fits. ResultsWhen multiple mediators are included, the total impact of DIs and SIs on survival is much reduced. Unlike the single mediator examples previously reported, the Yost, ADI and ICE-income indices do not display significant direct effects. This suggests that when important clinical mediators are included, the impact of neighborhood SES indices is significantly attenuated. It is also clear that certain behavioral and demographic measures such as physical activity, smoking, or adjusted family income do not have a significant role in survival when mediated by clinical factors. ConclusionMultiple mediation via clinical and diagnostic-related measures reduces the contextual effects of neighborhood measures on ovarian cancer survival. The robust association of the Kolak URB index on survival may be due to its relevance to access to care, unlike SES-based indices whose impact was significantly reduced when important clinical mediators were included.

The Significance of Comprehensive Metabolic Phenotypes in Cancer Risk: A Japan Multi-Institutional Collaborative Cohort (J-MICC) Study.

The present study investigated the relationship between metabolic phenotypes and the risk of cancer in a Japanese population using the criteria of metabolic phenotypes based on an examination and those based on questionnaires. We used data from 25,357 subjects for examination-based analyses and those from 53,042 subjects for questionnaire-based analyses in the Japan Multi-Institutional Collaborative Cohort Study. Metabolic phenotypes were defined by classifying subjects according to their BMI (obesity: BMI ≥25 kg/m2; normal weight: BMI <25 kg/m2) and the number of metabolic abnormalities. Metabolic abnormalities were defined according to metabolic syndrome components of the Joint Interim Statement Criteria for examination-based analyses and self-reported histories of diabetes, dyslipidemia, and hypertension for questionnaire-based analyses. Cox proportional hazards regression analyses adjusted for potential confounders were performed for total and site-specific cancer incidence according to metabolic phenotypes. Metabolically unhealthy obesity (MUHO) was significantly associated with cancer incidence in both examination-based [HR (95% CI): 1.17 (1.01-1.36)] and questionnaire-based analyses [HR (95% CI): 1.15 (1.04-1.26)]. Regarding site-specific cancer in questionnaire-based analyses, metabolically healthy obesity and MUHO were associated with colorectum and liver cancers in all subjects and with breast cancer in female subjects. Subjects with a metabolically unhealthy normal weight had a higher risk of pancreatic cancer. Moreover, MUHO was associated with corpus uteri cancer in female subjects. This prospective cohort study suggests that metabolic phenotypes are important risk factors for total and some site-specific cancers in Japanese adults.

Hormone Receptor Positive Breast Cancer in Young Women: A Review.

The global incidence of hormone-positive breast cancer (HR+ BC) in young women is rising, though the underlying reasons remain unclear. HR+ disease in younger women appears to represent a distinct clinical entity compared to that in older women, exhibiting distinct clinicopathological characteristics, outcomes and responses to treatment. Despite these differences, there is a paucity of large-volume data focusing on young women with HR+ in contemporary literature. Hormone receptor positive breast cancer in young women is associated with poorer prognoses compared to older women. Additionally, early age onset breast cancer presents unique challenges, including concerns related to fertility, the toxic effects of therapeutic agents, and specific surgical considerations. The purpose of this review is to report the existing literature on HR+ disease in young women.

The association between heart failure diagnosis and the incidence of cancer: a longitudinal analysis of the United Kingdom Biobank

Abstract Background Heart failure (HF) and cancer represent prevalent chronic conditions with a high burden of disease worldwide. Several studies have shown a high frequency of coexistence of these two entities, highlighting a potential bidirectional association. However, few longitudinal studies have explored whether patients with HF have a significantly increased risk of cancer and if comorbidity profiles affect this risk. Purpose To explore the association between incident HF diagnosis and cancer development in UK Biobank participants after adjustment by potential confounders. Methods We conducted a retrospective cohort study in UK Biobank. HF and cancer diagnoses were determined using diagnoses and patient reports. We evaluated breast, liver, lung, prostate, colorectal, uterus, and hematological cancer. Individuals with a history of HF or cancer diagnosed before the baseline assessment were excluded. The primary exposure was incident HF diagnosis after enrollment, and the primary outcome was incident cancer during follow-up. Multivariate Cox proportional hazard regression models using time-varying covariates were used to calculate hazard ratios (HR) for the explored associations with overall cancer and by major cancer type. A Bonferroni-corrected p-value &amp;lt; 0.003 was considered statistically significant to control for family-wise error rate. Results 476,652 patients were analyzed (mean age: 56.3 years; 57.8% females). Over a median follow-up of 13.7 years, 12,461 (2.6%) developed HF, and 34,452 (7.2%) were diagnosed with cancer. Incident HF was significantly associated with increased overall cancer risk (HR 1.34, 95% CI 1.22–1.48. p&amp;lt;0.001), as well as lung (HR 1.30, 95% CI 1.18–1.43), and hematological cancers (HR 1.54, 95% CI 1.25–1.91. p&amp;lt;0.001) (Figure). Conclusion Despite sharing multiple comorbidities and risk factors, incident HF remained significantly associated with a higher cancer risk even after multivariable adjustment by relevant confounders. Nevertheless, confounding bias and especially detection bias, cannot be ruled out in the present analysis. Further research is necessary to validate these findings and elucidate the mechanisms underlying this association.Figure

Social inequalities in cancer incidence, survival and mortality: An umbrella review

Abstract Background An increasing number of systematic reviews investigating differences in cancer burden by social factors such as race, ethnicity, and socioeconomic status have been published in recent years. Our study aims to evaluate the strength and quality of evidence from systematic reviews investigating associations between social factors and cancer incidence, survival, and mortality to help policy-makers reduce existing social inequalities in the burden of cancer. Methods Our study is a pre-registered umbrella review (PROSPERO; CRD42024552884). We systematically searched Medline, Scopus, Web of Science, CINAHL, PsycINFO, the Cochrane Library, the JBI EBP database, and Epistemonikos without date restrictions for published systematic reviews with or without meta-analyses on June 17, 2024. The search identified 15,542 records, which were reduced to 7,421 after deduplication. We are currently screening studies to include systematic reviews of cohort or case-control studies that examined associations between one or more social factors (gender, race/ethnicity, education, occupation, socioeconomic status, place of residence, religion, social capital) and cancer outcomes. Study screening, data extraction, and quality appraisal will be done in duplicate using pre-piloted forms. The strength of evidence of reported associations between social factors and cancer outcomes will be assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria. Before data synthesis, we will assess the degree of overlap between primary studies in the eligible reviews by creating citation matrices and calculating corrected covered area indices. Following this, we will narratively summarize associations (for systematic reviews without meta-analyses) and pool the risk estimates for individual social factors and cancer outcomes (for reviews with meta-analyses) using random-effects meta-analysis models. We will have preliminary results ready by November 2024. Key messages • Our umbrella review aims to evaluate the strength and quality of evidence from systematic reviews which have examined social inequalities in cancer incidence, survival, and mortality. • This high-level evidence synthesis can help policy-makers better plan and target interventions to reduce the existing social inequalities in the burden of cancer.

Blood pressure-lowering and risk of cancer: an individual participant-level data meta-analysis and mendelian randomisation studies

Abstract Background The current body of randomised evidence concerning the effect of blood pressure lowering on the risk of cancer remains limited. Purpose We leveraged the strengths of both randomised controlled trials (RCTs) and genomic information to examine this question. Methods Individual-level data from 314,016 participants from 42 RCTs were pooled to investigate the effect of blood pressure lowering on the risk of cancer through one-stage individual participant data (IPD) meta-analysis. The primary outcome was incident cancer, defined as the first occurrence of any cancer diagnosed after randomisation. Pre-specified subgroup analyses were conducted to assess heterogeneity in effect by follow-up time and baseline age groups, sex, body mass index categories, smoking status and previous use of antihypertensive drugs. Secondary outcomes were cause-specific cancer death and site-specific cancer risk comprising breast, colorectal, kidney, lung, prostate, and skin. Cox proportional hazard regression, stratified by trials, were used for statistical analyses. For site-specific cancers, analyses were complemented with Mendelian randomisation analyses using naturally randomised genetic variants associated with blood pressure lowering, retrieved from genome-wide association studies involving participants of European ancestry. Results Over a median of 4 years (interquartile range 2), 17,954 participants in RCTs were diagnosed with cancer of any type and 4,878 participants were reported to have died with cancer as the cause of death. In the IPD meta-analysis that compared the treatment arm with the comparator, no associations were identified between reductions in either systolic or diastolic blood pressure and the risk of incident cancer (hazard ratios [HRs] per 5 mmHg reduction in systolic and per 3 mmHg diastolic blood pressure were 1.03 (95% confidence interval [CI] 0.99-1.06) and 1.03 [0.98-1.07], respectively). We also found no pattern of increasing or decreasing relative risk for incident cancer during the follow-up period, nor was there evidence of heterogeneity in treatment effects across baseline subgroups. No effect on the risk of cause-specific cancer death was identified for either systolic or diastolic blood pressure lowering. Considering site-specific cancers, we also found no evidence of effect, except for a possible link with lung cancer risk, with HRs of 1.17 [99.5% CI 1.02-1.32] for systolic blood pressure and 1.17 [99.5% CI 0.98-1.36] for diastolic blood pressure lowering. In Mendelian randomisation studies, no association was observed for genetically determined systolic and diastolic blood pressure and all the considered site-specific cancers, including overall lung cancer and its subtypes. Conclusion We found no consistent randomised evidence to suggest that blood pressure-lowering has a substantial effect, whether increasing or decreasing, on incident cancer, cause-specific cancer death, or selected site-specific cancers.

Cancer incidence associations with drinking water arsenic levels and disinfection methods in Maine, USA

ABSTRACT Maine is a largely rural state where nearly half of the population uses drinking water from private wells. Arsenic (As) is present in some groundwater in the state and has been linked to cancer, and a lack of testing and treatment may expose people with private wells to elevated As levels. Disinfection byproducts (DBPs) include known and suspected carcinogens that form when chlorine or chloramines are added to water. People served by public water systems may be exposed to elevated levels of regulated DBPs such as trihalomethanes and haloacetic acids associated with chlorine and/or unregulated nitrogenous DBPs, or N-DBPs, such as nitrite and N-nitrosodimethylamine associated with chloramines. Contrary to initial expectations, there were no significant associations between median town As in well water and bladder, lung, kidney, or skin cancer incidence. Furthermore, bladder, melanoma, and other skin cancer incidence rates were negatively correlated with the percent of the town population using private wells. Analysis of cancer incidence associated with chlorine and chloramine disinfection showed elevated melanoma, and other skin cancer with chloramine use and elevated bladder and non-melanoma skin cancer with chlorine use compared to the no disinfectant case. We recommend more research on the links between disinfectant use and cancer.

Sex differences in cancer incidence amongst people with cardiovascular disease: a large British population study

Abstract Background Studies have shown that patients with cardiovascular disease (CVD) have an incremental risk of death due to noncardiac causes. This is especially attributable to cancer developments during long term follow up. The two diseases share pathophysiological mechanisms that extend beyond traditional risk factors. With well-established sex disparities in CVD, it becomes imperative to investigate whether similar sex-based differences exist in both the incidence of cancer and cancer-related mortality, in participants with CVD vs those without CVD. Purpose We aim to analyse the sex differences in incident cancer and cancer-related mortality between people with and without CVD. Methods Participants were drawn from a large British population based prospective cohort study and followed up for a median of 26.2 years. Participants were stratified by sex and whether they developed CVD over the study follow-up. The cumulative incidence of cancer, excluding non-melanoma skin cancers were calculated. Sex-specific lifetime risks were determined accounting for competing risks of death. Cause-specific hazard ratios were determined using Royston-Parmar models. Models were adjusted for ethnicity and time-updated covaries, including material deprivation, CV risk factors, lifestyle factors, comorbidities, and medication. Participants’ CVD status was time-updated over the study follow-up as this was diagnosed. Results Out of a total of 22, 534 participants, free of cancer at baseline, 53.7% were women. Mean (standard deviation) age was 58.6 (9.3) for women and 59.5 (9.3) for men, at baseline. Men were older and had more comorbidities. Hypertension and obesity were risk factors more prevalent amongst men, while women were more likely to be smokers at baseline. Participants with CVD had more comorbidities, were more likely to smoke, have higher HbA1cs and be obese than those without CVD. The adjusted lifetime risks of incident cancer in participants with CVD at age 75 were higher in men (13.9%) compared to women (10.1%). This translates into a cause-specific hazard ratio (cHR) (99% confidence interval) for incident cancer (men vs. women) of 1.41 (1.27 - 1.55). Similar findings were demonstrated in participants with no CVD (10.2% for men and 8.2% for women), corresponding to a cHR of 1.27 (1.15 - 1.40). Furthermore, men had a higher risk of cancer-related mortality compared to women in participants with CVD 1.54 (1.33 - 1.78), as well as among participants without CVD 1.34 (1.17 - 1.53). Conclusion Our study showed an association between CVD and the lifetime cancer risk in both sexes after extensive adjustment. Furthermore, we show that men have a higher risk of cancer incidence and cancer-related mortality than women, regardless of comorbid CVD. However, these associations, were stronger in participants with CVD. It is vital to identify driving forces of such disparities to achieve health equity.

Incidence, characteristics, and prognostic impact of cancers in patients with atrial fibrillation: a report from the GLORIA-AF registry

Abstract Background Cancers and atrial fibrillation (AF) are all aging-related diseases. Coexistence of the two conditions makes management complex due to increased risk of both thromboembolism and bleeding. Purpose The aim of the present study was to analyze the incidence and prognostic impact of cancers in patients with AF in the GLORIA-AF registry. Methods GLORIA-AF registry is a prospective multi-centered international multi-centered AF cohort studies. We characterized these patients according to the presence or absence of a cancer diagnosis when enrolled. The primary endpoints were all-cause mortality, cardiovascular mortality, and major bleeding; the secondary endpoints were major adverse cardiovascular events (MACEs) including all-cause mortality, stroke, and major bleeding. Results The prevalence of cancers was 9.7%. The mean CHA2DS2-VASc and HAS-BLED scores in cancer patients were higher than in non-cancer patients (mean CHA2DS2-VASc 3.5 vs. 3.2, P&amp;lt;0.001; mean HAS-BLED score 1.6 vs. 1.3, P&amp;lt;0.001). Patients with cancers had higher oral anticoagulant use than non-cancer patients (84.4% vs. 81.0%, P&amp;lt;0.001) and were more likely to receive NOACs (58.4% vs. 54.0%, P&amp;lt;0.001). During a mean follow up period of 3 years, AF patients with cancers had significantly higher all-cause mortality (15.0% vs. 8.3%, P&amp;lt;0.001), major bleeding rate (5.3% vs. 3.1%, P&amp;lt;0.001), the composite of all-cause mortality, stroke, and major bleeding (20.0% vs. 12.0%, P&amp;lt;0.001), and composite of all-cause mortality, thromboembolism, and major bleeding than non-cancer patients (21.0% vs. 12.0%, P&amp;lt;0.001), but nonsignificant differences in cardiovascular mortality (3.6% vs. 3.1%, P=0.2), any stroke, transient ischemic attack, or non-central nervous system embolism (3.2% vs. 2.7%, P=0.1), and OAC discontinuation (29.0% vs. 28%, P=0.2). Among the cancers, hematological cancer was associated the highest risk of all-cause mortality (HR=3.7, 95%CI 2.69-5.0, P&amp;lt;0.001) while respiratory cancer was associated the highest risk of major bleeding (HR=2.62, 95%CI 1.24-5.5, P=0.011). After multivariable adjustment, cancer was independently associated with increased risk of all-cause mortality (HR=1.30, 95%CI 1.05-1.62, P=0.018), composite of all-cause mortality, stroke, and major bleeding (HR=1.32, 95%CI 1.04-1.68, P=0.022), and composite of all-cause mortality, thromboembolism, and major bleeding (HR=1.29, 95%CI 1.04-1.60, P=0.022), but the risk of major bleeding was nonsignificantly different (HR=1.16, 95%CI 0.71-1.87, P=0.6). Conclusions Cancer is a common comorbidity in patients with AF and is independently associated with increased risk of poor outcomes including all-cause mortality and MACEs. However, cancer did not increase the risk of cardiovascular mortality, major bleeding, and discontinuation of OAC. Cancer in patients with AF should receive appropriate treatments for the cancer itself and appropriate OAC, although strategies may vary between different cancers.Distribution of caners in GLORIA-AFKaplan-Meier curves for the outcomes