Cancer‐specific survival after diagnosis in men versus women: A pan‐cancer analysis
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SUBMITTER: He Y
PROVIDER: S-EPMC9246337 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Importance:Survival differences between male and female patients with breast cancer have been reported, but the underlying factors associated with the disparity have not been fully studied. This understanding is fundamental to developing strategies for cancer treatment and survivorship care. Objective:To compare mortality between male and female patients with breast cancer and quantitatively evaluate the factors associated with sex-based disparity in mortality. Design, Setting, and Participants:This large, nationwide, registry-based cohort study used the National Cancer Database to identify and obtain data on patients who received a breast cancer diagnosis between January 1, 2004, and December 31, 2014. After exclusions, the final study population comprised 1?816?733 patients. Statistical analyses were conducted from September 1, 2018, to January 15, 2019. Main Outcomes and Measures:The primary outcome was overall survival. Secondary outcomes were 3-year and 5-year mortality. Mortality differences were evaluated by Kaplan-Meier analysis. The roles of race/ethnicity, clinical characteristics, treatments, and access-to-care factors in the association between sex and mortality were estimated by nested Cox proportional hazards regression models with adjustment for age. Results:In total, 16?025 male (mean [SD] age, 63.3 [13.0] years) and 1?800?708 female (mean [SD] age, 59.9 [13.3] years) patients with breast cancer were included in the study. Compared with female patients, male patients had higher mortality across all stages. For men, the overall survival rate was 45.8% (95% CI, 49.5-54.0; P?<?.001), the 3-year rate was 86.4% (95% CI, 85.9-87.0; P?<?.001), and the 5-year rate was 77.6% (95% CI, 76.8-78.3; P?<?.001). For women, the overall survival rate was 60.4% (95% CI, 58.7-62.0; P?<?.001), the 3-year rate was 91.7% (95% CI, 91.7-91.8; P?<?.001), and the 5-year rate was 86.4% (95% CI, 86.4-86.5; P?<?.001). Overall, clinical characteristics and undertreatments were associated with a 63.3% excess mortality rate for male patients. A higher proportion of excess deaths in men were explained by these factors in the first 3 years after breast cancer diagnosis (66.0%) and in all patients with early-stage cancer (30.5% for stage I and 13.6% for stage II). However, sex remained a significant factor associated with overall mortality (adjusted hazard ratio [HR], 1.19; 95% CI, 1.16-1.23) as well as mortality at 3-year (adjusted HR,?1.15; 95% CI, 1.10-1.21) and 5-year (adjusted HR,?1.19; 95% CI, 1.14-1.23) analyses, even after adjustment for clinical characteristics, treatment factors, age, race/ethnicity, and access to care. Conclusions and Relevance:This study found that mortality after cancer diagnosis was higher among male patients with breast cancer compared with their female counterparts. Such disparity appeared to persist after accounting for clinical characteristics, treatment factors, and access to care, suggesting that other factors (particularly additional biological attributes, treatment compliance, and lifestyle factors) should be identified to help in eliminating this disparity.
| S-EPMC6753503 | biostudies-literature
Project description:As tumors accumulate genetic alterations, an evolutionary process occurs in which genetically distinct subclonal populations of cells co-exist, resulting in intratumor genetic heterogeneity (ITH). The clinical implications of ITH remain poorly defined. Data are limited with respect to whether ITH is an independent determinant of patient survival outcomes, across different cancer types. Here, we report the results of a pan-cancer analysis of over 3300 tumors, showing a varied landscape of ITH across 9 cancer types. While some gene mutations are subclonal, the majority of driver gene mutations are clonal events, present in nearly all cancer cells. Strikingly, high levels of ITH are associated with poorer survival across diverse types of cancer. The adverse impact of high ITH is independent of other clinical, pathologic and molecular factors. High ITH tends to be associated with lower levels of tumor-infiltrating immune cells, but this association is not able to explain the observed survival differences. Together, these data show that ITH is a prognostic marker in multiple cancers. These results illuminate the natural history of cancer evolution, indicating that tumor heterogeneity represents a significant obstacle to cancer control.
| S-EPMC4891103 | biostudies-other
Project description:Although previous studies have suggested a potential role of sex hormones in the etiology of colorectal cancer (CRC), no study has yet examined the associations between circulating sex hormones and survival among CRC patients. We prospectively assessed the associations of prediagnostic plasma concentrations of estrone, estradiol, free estradiol, testosterone, free testosterone and sex hormone-binding globulin (SHBG) with CRC-specific and overall mortality among 609 CRC patients (370 men and 239 postmenopausal women not taking hormone therapy at blood collection) from four U.S. cohorts. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard regression. We identified 174 deaths (83 CRC-specific deaths) in men and 106 deaths (70 CRC-specific deaths) in women. In men, higher circulating level of free testosterone was associated with lower risk of overall (the highest vs. lowest tertiles, HR = 0.66, 95% CI, 0.45-0.99, ptrend = 0.04) and possibly CRC-specific mortality (HR = 0.73, 95% CI, 0.41-1.29, ptrend = 0.27). We generally observed nonsignificant inverse associations for other sex steroids, and a positive association for SHBG with CRC-specific mortality among male patients. In women, however, we found a suggestive positive association of estrone with overall (HR = 1.54, 95% CI, 0.92-2.60, ptrend = 0.11) and CRC-specific mortality (HR = 1.96, 95% CI, 1.01-3.84, ptrend = 0.06). Total estradiol, free estradiol and free testosterone were generally suggestively associated with higher risk of mortality among female patients, although not statistically significant. These findings implicated a potential role of endogenous sex hormones in CRC prognosis, which warrant further investigation.
| S-EPMC7895324 | biostudies-literature
Project description:BackgroundDietary factors are known to influence colorectal cancer (CRC) risk, however, their association with CRC survival is unclear. Therefore, we prospectively examined the association between diet quality scores, dietary patterns and colorectal cancer (CRC) survival.Methods1201 women diagnosed with stage I-III CRC between 1986 and 2008, were followed through 2010. Diet was assessed via a food frequency questionnaire administered at least 6 months after diagnosis. We computed the Alternate Healthy Eating Index-2010 (AHEI-2010), alternate Mediterranean Diet score (aMED) and Dietary Approaches to Stop Hypertension score (DASH) and derived two dietary patterns, Western (unhealthy) and prudent (healthy), by principal component analysis for each woman.ResultsDuring follow-up, we documented 435 deaths, including 162 from CRC. After adjusting for potential confounders, only a higher AHEI-2010 score was significantly associated with lower overall mortality (HR comparing extreme quintiles?=?0.71, 95% CI 0.52-0.98, p trend?=?0.01) as well as borderline significantly with lower risk of CRC mortality by the trend test (HR Q5 vs Q1?=?0.72, 95% CI?=?0.43-1.21, p trend?=?0.07). When AHEI-2010 components were examined separately, inverse associations for overall mortality were primarily accounted for by moderate alcohol intake (HR comparing abstainers vs 5-15 g/d?=?1.30, 95%CI?=?1.05-1.61) and lower intake of sugar sweetened beverages and fruit juices combined (HR for each additional serving?=?1.11, 95% CI?=?1.01-1.23). No other diet quality score or dietary pattern was associated with overall or CRC-specific mortality.ConclusionHigher AHEI-2010 score may be associated with lower overall mortality, moderate alcohol consumption and lower consumption of sugar sweetened beverages and juices combined appeared to account for most of the observed associations.
| S-EPMC4266679 | biostudies-literature
Project description:BackgroundAbnormal metabolism and perturbations in metabolic pathways play significant roles in the development and progression of prostate cancer; however, comprehensive metabolomic analyses of human data are lacking and needed to elucidate the interrelationships.MethodsWe examined the serum metabolome in relation to prostate cancer survival in a cohort of 1812 cases in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. Using an ultrahigh-performance LC-MS/MS platform, we identified 961 known metabolites in prospectively collected serum. Median survival time from diagnosis to prostate cancer-specific death (N=472) was 6.6 years (interquartile range=2.9-11.1 years). Cox proportional hazards regression models estimated hazard ratios and 95% confidence intervals of the associations between the serum metabolites (in quartiles) and prostate cancer death, adjusted for age at baseline and diagnosis, disease stage, and Gleason sum. In order to calculate risk scores, we first randomly divided the metabolomic data into a discovery set (70%) and validated in a replication set (30%).ResultsOverall, 49 metabolites were associated with prostate cancer survival after Bonferroni correction. Notably, higher levels of the phospholipid choline, amino acid glutamate, long-chain polyunsaturated fatty acid (n6) arachidonate (20:4n6), and glutamyl amino acids gamma-glutamylglutamate, gamma-glutamylglycine, and gamma-glutamylleucine were associated with increased risk of prostate cancer-specific mortality (fourth versus first quartile HRs=2.07-2.14; P-values <5.2×10-5). By contrast, the ascorbate/aldarate metabolite oxalate, xenobiotics S-carboxymethyl-L-cysteine, fibrinogen cleavage peptides ADpSGEGDFXAEGGGVR and fibrinopeptide B (1-12) were related to reduced disease-specific mortality (fourth versus first quartile HRs=0.82-0.84; P-value <5.2×10-5). Further adjustment for years from blood collection to cancer diagnosis, body mass index, smoking intensity and duration, and serum total and high-density lipoprotein cholesterol did not alter the results. Participants with a higher metabolic score based on the discovery set had an elevated risk of prostate cancer-specific mortality in the replication set (fourth versus first quartile, HR=3.9, P-value for trend<0.0001).ConclusionsThe metabolic traits identified in this study, including for choline, glutamate, arachidonate, gamma-glutamyl amino acids, fibrinopeptides, and endocannabinoid and redox pathways and their composite risk score, corroborate our previous analysis of fatal prostate cancer and provide novel insights and potential leads regarding the molecular basis of prostate cancer progression and mortality.
| S-EPMC9594924 | biostudies-literature
Project description:ObjectivesTo determine the lung cancer incidence and survival time among HIV-infected and uninfected women and men.DesignTwo longitudinal studies of HIV infection in the United States.MethodsData from 2549 women in the Women's Interagency HIV Study (WIHS) and 4274 men in the Multicenter AIDS Cohort Study (MACS), all with a history of cigarette smoking, were analyzed. Lung cancer incidence rates and incidence rate ratios were calculated using Poisson regression analyses. Survival time was assessed using Kaplan-Meier and Cox proportional-hazard analyses.ResultsThirty-seven women and 23 men developed lung cancer (46 HIV-infected and 14 HIV-uninfected) during study follow-up. In multivariable analyses, the factors that were found to be independently associated with a higher lung cancer incidence rate ratios were older age, less education, 10 or more pack-years of smoking, and a prior diagnosis of AIDS pneumonia (vs. HIV-uninfected women). In an adjusted Cox model that allowed different hazard functions for each cohort, a history of injection drug use was associated with shorter survival, and a lung cancer diagnosis after 2001 was associated with longer survival. In an adjusted Cox model restricted to HIV-infected participants, nadir CD4 lymphocyte cell count less than 200 was associated with shorter survival time.ConclusionsOur data suggest that pulmonary damage and inflammation associated with HIV infection may be causative for the increased risk of lung cancer. Encouraging and assisting younger HIV-infected smokers to quit and to sustain cessation of smoking is imperative to reduce the lung cancer burden in this population.
| S-EPMC4457511 | biostudies-literature
Project description:PURPOSE:Treatment decisions about localized prostate cancer depend on accurate estimation of the patient's life expectancy. Current cancer and noncancer survival models use a limited number of predefined variables, which could restrict their predictive capability. We explored a technique to create more comprehensive survival prediction models using insurance claims data from a large administrative data set. These data contain substantial information about medical diagnoses and procedures, and thus may provide a broader reflection of each patient's health. METHODS:We identified 57,011 Medicare beneficiaries with localized prostate cancer diagnosed between 2004 and 2009. We constructed separate cancer survival and noncancer survival prediction models using a training data set and assessed performance on a test data set. Potential model inputs included clinical and demographic covariates, and 8,971 distinct insurance claim codes describing comorbid diseases, procedures, surgeries, and diagnostic tests. We used a least absolute shrinkage and selection operator technique to identify predictive variables in the final survival models. Each model's predictive capacity was compared with existing survival models with a metric of explained randomness (ρ2) ranging from 0 to 1, with 1 indicating an ideal prediction. RESULTS:Our noncancer survival model included 143 covariates and had improved survival prediction (ρ2 = 0.60) compared with the Charlson comorbidity index (ρ2 = 0.26) and Elixhauser comorbidity index (ρ2 = 0.26). Our cancer-specific survival model included nine covariates, and had similar survival predictions (ρ2 = 0.71) to the Memorial Sloan Kettering prediction model (ρ2 = 0.68). CONCLUSION:Survival prediction models using high-dimensional variable selection techniques applied to claims data show promise, particularly with noncancer survival prediction. After further validation, these analyses could inform clinical decisions for men with prostate cancer.
| S-EPMC6873997 | biostudies-literature
Project description:DNA methylation status is closely associated with diverse diseases, and is generally more stable than gene expression, thus abnormal DNA methylation could be important biomarkers for tumor diagnosis, treatment and prognosis. However, the signatures regarding DNA methylation changes for pan-cancer diagnosis and prognosis are less explored. Here we systematically analyzed the genome-wide DNA methylation patterns in diverse TCGA cancers with machine learning. We identified seven CpG sites that could effectively discriminate tumor samples from adjacent normal tissue samples for 12 main cancers of TCGA (1216 samples, AUC > 0.99). Those seven potential diagnostic biomarkers were further validated in the other 9 different TCGA cancers and 4 independent datasets (AUC > 0.92). Three out of the seven CpG sites were correlated with cell division, DNA replication and cell cycle. We also identified 12 CpG sites that can effectively distinguish 26 different cancers (7605 samples), and the result was repeatable in independent datasets as well as two disparate tumors with metastases (micro-average AUC > 0.89). Furthermore, a series of potential signatures that could significantly predict the prognosis of tumor patients for 7 different cancer were identified via survival analysis (p-value < 1e-4). Collectively, DNA methylation patterns vary greatly between tumor and adjacent normal tissues, as well as among different types of cancers. Our identified signatures may aid the decision of clinical diagnosis and prognosis for pan-cancer and the potential cancer-specific biomarkers could be used to predict the primary site of metastatic breast and prostate cancers.
| S-EPMC6380428 | biostudies-literature
Project description:The processes of cancer initiation, progression, and response to therapy are affected by the sex of cancer patients. Immunotherapy responses largely depend on the tumor microenvironment (TME), but how sex may shape some TME features, remains unknown. Here, we analyzed immune infiltration signatures across 19 cancer types from 1771 male and 1137 female patients in The Cancer Genome Atlas to evaluate how sex may affect the tumor mutational burden (TMB), immune scores, stromal scores, tumor purity, immune cells, immune checkpoint genes, and functional pathways in the TME. Pan-cancer analyses showed higher TMB and tumor purity scores, as well as lower immune and stromal scores in male patients as compared to female patients. Lung adenocarcinoma, lung squamous carcinoma, kidney papillary carcinoma, and head and neck squamous carcinoma showed the most significant sex biases in terms of infiltrating immune cells, immune checkpoint gene expression, and functional pathways. We further focused on lung adenocarcinoma samples in order to identify and validate sex-specific immune cell biomarkers with prognostic potential. Overall, sex may affect the tumor microenvironment, and sex-specific TME biomarkers may help tailor cancer immunotherapy in certain cancer types.
| S-EPMC9168759 | biostudies-literature
Project description: Not available
| S-EPMC8411278 | biostudies-literature