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Purpose: Investigating the association between red cell distribution width (RDW) and all-cause mortality in patients with breast cancer, to evaluate the potential clinical prognostic value of RDW. Methods: Based on the RDW index, patients with breast cancer in the Medical Information Mart for Intensive Care (MIMIC-IV) database were categorized into quartiles. The primary outcomes included in-hospital mortality from all causes during the first six months, the first year, and the first three years. Cox hazards regression and restricted cubic spline (RCS) models were developed to investigate the effects of RDW on primary outcomes. Results: The study included 939 patients (female). The 6-month, 1-year, and 3-year mortality rates were 14.0%, 21.4%, and 28.4%, respectively. Multivariate Cox proportional hazards analyses demonstrated that RDW exhibited an autonomous association with an increased risk of all-cause mortality. After adjusting for confounders, higher RDW quartiles were significantly associated with 6-month mortality (adjusted hazard ratio (HR), 3.197; 95% confidence interval (CI), 1.745–5.762; P < 0.001), 1-year mortality (adjusted HR, 2.978; 95% CI, 1.867–4.748; P < 0.001), and 3-year mortality (adjusted HR, 2.526; 95% CI, 1.701–3.750; P < 0.001). The RCS curves demonstrated that high RDW (> 14.6) was associated with a greater risk of all-cause mortality. Subgroup analyses revealed no statistically significant differences in the interactions between the subgroups. Conclusion: The study revealed a highly pronounced relationship between RDW and overall mortality, indicating its potential as an autonomous prognostic factor for increased mortality among patients with breast cancer. [ABSTRACT FROM AUTHOR]

Background: Evidence regarding the impact of nurse staffing on the health outcomes of older adult patients with cancer is scarce. Therefore, this study aimed to evaluate the impact of nurse staffing on long-term and short-term mortality in elderly lung cancer patients. Methods: This study analyzed data from 5,832 patients with lung cancer in Korea from 2008 to 2018. Nursing grade was considered to assess the effect of nursing staff on mortality in older adult patients with lung cancer. The Cox proportional hazards model was used to evaluate the effect of the initial treatment hospital's nursing grade on one- and five-year mortality. Additionally, economic status and treatment type of patients were analyzed. Results: Approximately 31% of older adult patients with lung cancer died within one year post-diagnosis. Patients in hospitals with superior nursing grades (lower nurse-to-bed ratios) exhibited lower mortality rates. Hospitals with nursing grades 2 and 3 exhibited approximately 1.242–1.289 times higher mortality than grade 1 hospitals. Further, the lower the nursing grade (higher nurse-to-bed ratio), the higher the five-year mortality rate. Conclusion: Both short- and long-term mortality rates for older adult patients with lung cancer increased at inferior nursing grades. Treatment in hospitals having inferior nursing grades, upon initial hospitalization, may yield better outcomes. This study provides valuable insight into the quality of adequate staffing to improve the quality of care for elderly cancer patients. [ABSTRACT FROM AUTHOR]

Background: Patients diagnosed with stage III breast cancer often undergo surgery, radiation therapy, and chemotherapy as part of their treatment. The choice of anesthesia technique during surgery has been a subject of interest due to its potential association with immune changes and prognosis. In this study, we aimed to compare the mortality rates between stage III breast cancer patients undergoing surgery with propofol-based intravenous general anesthesia and those receiving inhaled anesthetics. Methods: Using data from Taiwan's National Health Insurance Research Database and Taiwan Cancer Registry, we identified a cohort of 10,896 stage III breast cancer patients. Among them, 1,506 received propofol-based intravenous anesthetic maintenance, while 9,390 received inhaled anesthetic maintenance. To ensure comparability between the two groups, we performed propensity-score matching. Results: Our findings revealed a significantly lower mortality rate in patients who received inhaled anesthetics compared to those who received propofol-based intravenous anesthesia. Sensitivity analysis further confirmed the robustness of our results. Conclusions: This study suggests that inhaled anesthesia technique is associated with a lower mortality rate in clinical stage III breast cancer. Further research is needed to validate and expand upon these results. [ABSTRACT FROM AUTHOR]

Objective: Combined pulmonary fibrosis and emphysema (CPFE) is a syndrome characterized by the coexistence of emphysema and fibrotic interstitial lung disease (ILD). The aim of this study was to examine the effect of CPFE on lung cancer risk and lung cancer-related mortality in patients with rheumatoid arthritis (RA). Methods: We conducted a multicenter retrospective cohort study of patients newly diagnosed with lung cancer at five community hospitals between June 2006 and December 2021. Patients were followed until lung cancer-related death, other-cause death, loss to follow-up, or the end of the study. We used the cumulative incidence function with Gray's test and Fine-Gray regression analysis for survival analysis. Results: A total of 563 patients with biopsy-proven lung cancer were included (82 RA patients and 481 non-RA patients). The prevalence of CPFE was higher in RA patients than in non-RA patients (40.2% vs.10.0%) at lung cancer diagnosis. During follow-up, the crude incidence rate of lung cancer-related death was 0.29 and 0.10 per patient-year (PY) in RA and non-RA patients, and 0.32 and 0.07 per PY in patients with CPFE and patients without ILD or emphysema, respectively. The estimated death probability at 5 years differed between RA and non-RA patients (66% vs. 32%, p<0.001) and between patients with CPFE and patients without ILD or emphysema (71% vs. 24%, p<0.001). In addition to clinical cancer stage and no surgery within 1 month, RA and CPFE were identified as independent predictive factors for increased lung cancer-related mortality (RA: adjusted hazard ratio [HR], 2.49; 95% confidence interval [CI], 1.65–4.76; CPFE: adjusted HR 2.01; 95% CI 1.24–3.23). Conclusions: RA patients with lung cancer had a higher prevalence of CPFE and increased cancer-related mortality compared with non-RA patients. Close monitoring and optimal treatment strategies tailored to RA patients with CPFE are important to improve the poor prognosis of lung cancer. [ABSTRACT FROM AUTHOR]

Patricia Mabry and coauthors discuss application of systems approaches in cancer research. [ABSTRACT FROM AUTHOR]

Breast cancer is a major health problem worldwide. Analysis of breast cancer epidemiology in emerging countries enables assessment of prognostic factors, cancer care quality, and the equity of resource distribution. We aimed to estimate the overall (OS) and cancer-specific survival (SS) of breast cancer patients in the northeastern Brazilian state of Sergipe to identify independent prognostic factors. We analyzed a cohort for the factors age at diagnosis, place of residence, time to treatment, staging, and molecular classification, using the Kaplan–Meier method, log-rank test, Pearson's chi-squared test and Cox regression model. The outcome was the vital status at the end of the study. Our analysis showed an OS probability of 0.72 and an SS probability of 0.75. In multivariate analysis, time to treatment within 60 days, stage IV, and triple-negative classification remained independent prognostic factors for both OS [unadjusted hazard ratio (HRp) 1.50 (1.21; 1.86), HRp 16.56 (8.35; 32.85), and HRp 2.73 (1.73; 4.29), respectively] and SS [HRp 1.43 (1.13; 1.81), HRp 20.53 (9.45; 44.56), and HRp 3.14 (1.88; 5.26), respectively]. Better survival was demonstrated for the following patients: those receiving their first treatment after 60 days, with an OS of 52.5 months (51.2; 53.8) and SS of 53.5 months (52.3; 54.7); stage I patients, with an OS of 58.8 months (57.7; 60.0) and SS of 59.2 months (58.1; 60.3); patients without nodal metastasis, with an OS of 54.2 months (53.0; 55.4) and SS of 55.6 months (54.5; 56.7); and patients with luminal A classification, with an OS of 56.8 months (55.0; 58.5) and SS of 57.8 months (56.2; 59.4). This study identified independent prognostic factors and that OS and SS were lower for patients from Sergipe than for patients in high-income areas. Therefore, determining the profiles of breast cancer patients in this population will inform specific cancer care. [ABSTRACT FROM AUTHOR]

Systems epidemiology offers a more comprehensive and holistic approach to studies of cancer in populations by considering high dimensionality measures from multiple domains, assessing the inter-relationships among risk factors, and considering changes over time. These approaches offer a framework to account for the complexity of cancer and contribute to a broader understanding of the disease. Therefore, NCI sponsored a workshop in February 2019 to facilitate discussion about the opportunities and challenges of the application of systems epidemiology approaches for cancer research. Eight key themes emerged from the discussion: transdisciplinary collaboration and a problem-based approach; methods and modeling considerations; interpretation, validation, and evaluation of models; data needs and opportunities; sharing of data and models; enhanced training practices; dissemination of systems models; and building a systems epidemiology community. This manuscript summarizes these themes, highlights opportunities for cancer systems epidemiology research, outlines ways to foster this research area, and introduces a collection of papers, "Cancer System Epidemiology Insights and Future Opportunities" that highlight findings based on systems epidemiology approaches. [ABSTRACT FROM AUTHOR]

Background: As oesophageal cancer has short survival, it is likely pre-diagnosis health behaviours will have carry-over effects on post-diagnosis survival times. Cancer registry data sets do not usually contain pre-diagnosis health behaviours and so need to be augmented with data from external health surveys. A new algorithm is introduced and tested to augment cancer registries with external data when one-to-one data linkage is not available. Methods: The algorithm is to use external health survey data to impute pre-diagnosis health behaviour for cancer patients, estimate misclassification errors in these imputed values and then fit misclassification corrected Cox regression to quantify the association between pre-diagnosis health behaviour and post-diagnosis survival. Data from US cancer registries and a US national health survey are used in testing the algorithm. Results: It is demonstrated that the algorithm works effectively on simulated smoking data when there is no age confounding. But age confounding does exist (risk of death increases with age and most health behaviours change with age) and interferes with the performance of the algorithm. The estimate of the hazard ratio (HR) of pre-diagnosis smoking was HR = 1.32 (95% CI 0.82,2.68) with HR = 1.93 (95% CI 1.08,7.07) in the squamous cell sub-group and pre-diagnosis physical activity was protective of survival with HR = 0.25 (95% CI 0.03, 0.81). But the method failed for less common behaviours (such as heavy drinking). Conclusions: Further improvements in the I2C2 algorithm will permit enrichment of cancer registry data through imputation of new variables with negligible risk to patient confidentiality, opening new research opportunities in cancer epidemiology. [ABSTRACT FROM AUTHOR]

Objectives: Systems epidemiology approaches may lead to a better understanding of the complex and dynamic multi-level constellation of contributors to cancer risk and outcomes and help target interventions. This grant portfolio analysis aimed to describe the National Institutes of Health (NIH) and the National Cancer Institute (NCI) investments in systems epidemiology and to identify gaps in the cancer systems epidemiology portfolio. Methods: The analysis examined grants funded (2013–2018) through seven NIH systems science Funding Opportunity Announcements (FOAs) as well as cancer-specific systems epidemiology grants funded by NCI during that same time. Study characteristics were extracted from the grant abstracts and specific aims and coded. Results: Of the 137 grants awarded under the NIH FOAs, 52 (38%) included systems epidemiology. Only five (4%) were focused on cancer systems epidemiology. The NCI-wide search (N = 453 grants) identified 35 grants (8%) that included cancer systems epidemiology in their specific aims. Most of these grants examined epidemiology and surveillance-based questions (60%); fewer addressed clinical care or clinical trials (37%). Fifty-four percent looked at multiple scales within the individual (e.g., cell, tissue, organ), 49% looked beyond the individual (e.g., individual, community, population), and few (9%) included both. Across all grants examined, the systems epidemiology grants primarily focused on discovery or prediction, rather than on impacts of intervention or policy. Conclusions: The most notable finding was that grants focused on cancer versus other diseases reflected a small percentage of the portfolio, highlighting the need to encourage more cancer systems epidemiology research. Opportunities include encouraging more multiscale research and continuing the support for broad examination of domains in these studies. Finally, the nascent discipline of systems epidemiology could benefit from the creation of standard terminology and definitions to guide future progress. [ABSTRACT FROM AUTHOR]

Background: Identifying stage II patients with colorectal cancer (CRC) at higher risk of progression is a clinical priority in order to optimize the advantages of adjuvant chemotherapy while avoiding unnecessary toxicity. Recently, the intensity and the quality of the host immune response in the tumor microenvironment have been reported to have an important role in tumorigenesis and an inverse association with tumor progression. This association is well established in microsatellite instable CRC. In this work, we aim to assess the usefulness of measures of T-cell infiltration as prognostic biomarkers in 640 stage II, CRC tumors, 582 of them confirmed microsatellite stable.Methods and Findings: We measured both the quantity and clonality index of T cells by means of T-cell receptor (TCR) immunosequencing in a discovery dataset (95 patients with colon cancer diagnosed at stage II and microsatellite stable, median age 67, 30% women) and replicated the results in 3 additional series of stage II patients from 2 countries. Series 1 and 2 were recruited in Barcelona, Spain and included 112 fresh frozen (FF, median age 69, 44% women) and 163 formalin-fixed paraffin-embedded (FFPE, median age 67, 39% women) samples, respectively. Series 3 included 270 FFPE samples from patients recruited in Haifa, Northern Israel, as part of a large case-control study of CRC (median age 73, 46% women). Median follow-up time was 81.1 months. Cox regression models were fitted to evaluate the prognostic value of T-cell abundance and Simpson clonality of TCR variants adjusting by sex, age, tumor location, and stage (IIA and IIB). In the discovery dataset, higher TCR abundance was associated with better prognosis (hazard ratio [HR] for ≥Q1 = 0.25, 95% CI 0.10-0.63, P = 0.003). A functional analysis of gene expression on these tumors revealed enrichment in pathways related to immune response. Higher values of clonality index (lower diversity) were not associated with worse disease-free survival, though the HR for ≥Q3 was 2.32 (95% CI 0.90-5.97, P = 0.08). These results were replicated in an independent FF dataset (TCR abundance: HR = 0.30, 95% CI 0.12-0.72, P = 0.007; clonality: HR = 3.32, 95% CI 1.38-7.94, P = 0.007). Also, the association with prognosis was tested in 2 independent FFPE datasets. The same association was observed with TCR abundance (HR = 0.41, 95% CI 0.18-0.93, P = 0.03 and HR = 0.56, 95% CI 0.31-1, P = 0.042, respectively, for each FFPE dataset). However, the clonality index was associated with prognosis only in the FFPE dataset from Israel (HR = 2.45, 95% CI 1.39-4.32, P = 0.002). Finally, a combined analysis combining all microsatellite stable (MSS) samples demonstrated a clear prognosis value both for TCR abundance (HR = 0.39, 95% CI 0.26-0.57, P = 1.3e-06) and the clonality index (HR = 2.13, 95% CI 1.44-3.15, P = 0.0002). These associations were also observed when variables were considered continuous in the models (HR per log2 of TCR abundance = 0.85, 95% CI 0.78-0.93, P = 0.0002; HR per log2 or clonality index = 1.16, 95% CI 1.03-1.31, P = 0.016).Limitations: This is a retrospective study, and samples had been preserved with different methods. Validation series lack complete information about microsatellite instability (MSI) status and pathology assessment. The Molecular Epidemiology of Colorectal Cancer (MECC) study had information about overall survival instead of progression-free survival.Conclusion: Results from this study demonstrate that tumor lymphocytes, assessed by TCR repertoire quantification based on a sequencing method, are an independent prognostic factor in microsatellite stable stage II CRC. [ABSTRACT FROM AUTHOR]

The purpose of this study was to identify germline single nucleotide polymorphisms (SNPs) that optimally predict radiation-associated contralateral breast cancer (RCBC) and to provide new biological insights into the carcinogenic process. Fifty-two women with contralateral breast cancer and 153 women with unilateral breast cancer were identified within the Women's Environmental Cancer and Radiation Epidemiology (WECARE) Study who were at increased risk of RCBC because they were ≤ 40 years of age at first diagnosis of breast cancer and received a scatter radiation dose > 1 Gy to the contralateral breast. A previously reported algorithm, preconditioned random forest regression, was applied to predict the risk of developing RCBC. The resulting model produced an area under the curve (AUC) of 0.62 (p = 0.04) on hold-out validation data. The biological analysis identified the cyclic AMP-mediated signaling and Ephrin-A as significant biological correlates, which were previously shown to influence cell survival after radiation in an ATM-dependent manner. The key connected genes and proteins that are identified in this analysis were previously identified as relevant to breast cancer, radiation response, or both. In summary, machine learning/bioinformatics methods applied to genome-wide genotyping data have great potential to reveal plausible biological correlates associated with the risk of RCBC. [ABSTRACT FROM AUTHOR]

Estimating and selecting risk factors with extremely low prevalences of exposure for a binary outcome is a challenge because classical standard techniques, markedly logistic regression, often fail to provide meaningful results in such settings. While penalized regression methods are widely used in high-dimensional settings, we were able to show their usefulness in low-dimensional settings as well. Specifically, we demonstrate that Firth correction, ridge, the lasso and boosting all improve the estimation for low-prevalence risk factors. While the methods themselves are well-established, comparison studies are needed to assess their potential benefits in this context. This is done here using the dataset of a large unmatched case-control study from France (2005-2008) about the relationship between prescription medicines and road traffic accidents and an accompanying simulation study. Results show that the estimation of risk factors with prevalences below 0.1% can be drastically improved by using Firth correction and boosting in particular, especially for ultra-low prevalences. When a moderate number of low prevalence exposures is available, we recommend the use of penalized techniques. [ABSTRACT FROM AUTHOR]

Background: Epidemiologic findings of low-volume alcohol consumption in relation to gastrointestinal cancers including gastric cancer are inconsistent. Methods: The association between alcohol intake and esophageal, gastric and colorectal cancer risk was examined in a population-based prospective cohort of 23,323,730 adults in Korea who had undergone a biennial evaluation provided by the National Health Insurance Corporation between the years 2009 and 2012. After median 5.4 years of follow-up, 9,171 esophageal, 135,382 gastric and 154,970 colorectal cancer cases were identified. Cox regression models were used to estimate hazard ratios (HR) and corresponding 95% confidence intervals (95% CI). Results: Light drinking as well as moderate to heavy alcohol consumption significantly increased the risks of the three gastrointestinal cancers (HR 1.51; 95% CI, 1.43–1.60; HR 1.08; 95% CI, 1.06–1.09; HR 1.12; 95% CI, 1.11–1.14) compared with non-drinkers after adjusting for age, sex, smoking, exercise, income, body mass index, and diabetes. The synergistically increased cancer risk between excessive amount of alcohol consumption and currently smoking or underweight individuals was observed only in the esophageal cancers. Conclusions: Light drinking including even one alcoholic drink a day is associated with increased risks of esophageal, gastric and colorectal cancer. [ABSTRACT FROM AUTHOR]

Purpose: Signet ring cell carcinoma of the esophagus (SRCCE) is an uncommon tumor associated with significant morbidity and mortality. There is still no consensus regarding cut-off values for tumor size, age and optimal treatment for SRCCE. Thus, we elucidated the current survival outcomes of patients with SRCCE and analyzed factors associated with prognosis. Methods: A retrospective cohort study based on the SEER (The Surveillance, Epidemiology, and End Results) program database was conducted. We identified 537 patients (461 men and 76 women) newly diagnosed with SRCCE between January 2004 and December 2014. A multivariate Cox proportional hazards model was utilized to measure the mortality-associated risk factors in patients with SRCCE after adjusting for various variables. Results: The 1-, 2- and 5-year disease-specific mortalities (DSM) were 51.6%, 67.6%, and 78.4%, respectively, and the median survival time was 12.0 months. The factors correlated with mortality hazard were marital status (unmarried versus married, Hazard Ratio (HR) = 1.443), tumor size (≥ 5 cm versus < 5 cm, HR = 1.444), tumor grade (high grade versus low grade, HR = 3.001), condition of primary tumor (T4 versus T1, HR = 2.178), regional lymph node metastasis (N1 versus N0, HR = 1.739), further metastasis (M1 versus M0, HR = 1.951) and chemotherapy (receiving chemotherapy versus no chemotherapy, HR = 0.464). Conclusions: The contemporary 5-year DSM was 78.4%. Being unmarried, having a tumor size ≥ 5 cm, a high tumor grade, a score of T4 for tumor invasion of adjacent organs, a score of N1 for regional lymph node metastasis, a score of M1 for distant metastasis and no chemotherapy were independent predictors of high DSM. [ABSTRACT FROM AUTHOR]

Cancer incidence is rising among adolescents (“teens”). The causes of the increase are unknown but studying incidence patterns and trends may produce insights into etiology. Using data from the US National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program we described trends of cancer incidence among teens (15–19 year olds). We reviewed and summarized incidence patterns for histologic cancer groups and the most frequently diagnosed sites of cancer among teens during 2008–2012 reported by the SEER Cancer Statistics Review. We calculated annual incidence rates for the years 1975–2012 and used linear regression analysis to evaluate trends and calculate rates of change. Incidence for all sites combined increased annually by 0.67% for males and 0.62% for females during the period 1975 through 2012 –resulting in more than a 25% increase over 38 years. The biggest annual incidence increases occurred in non-Hodgkin lymphoma (NHL) (2.16% females; 1.38% males), thyroid cancer (2.12% females; 1.59% males), acute myeloid leukemia (AML) (1.73% females) and testicular cancer (1.55% males). Incidence rates for most histologic groups and sites showed steady long term increases over the 38 years of data. Despite improvements in survival, rising incidence trends mean growing numbers of young adults are undergoing painful and costly cancer treatments. A concerted research program is vital to investigate causes of steadily rising teen cancer rates. [ABSTRACT FROM AUTHOR]

Background: The features related to the prognosis of patients with mucinous breast cancer (MBC) remain controversial. We aimed to explore the prognostic factors of MBC and develop a nomogram for predicting survival outcomes. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was searched to identify 139611 women with resectable breast cancer from 1990 to 2007. Survival curves were generated using Kaplan-Meier methods. The 5-year and 10-year cancer-specific survival (CSS) rates were calculated using the Life-Table method. Based on Cox models, a nomogram was constructed to predict the probabilities of CSS for an individual patient. The competing risk regression model was used to analyse the specific survival of patients with MBC. Results: There were 136569 (97.82%) infiltrative ductal cancer (IDC) patients and 3042 (2.18%) MBC patients. Patients with MBC had less lymph node involvement, a higher frequency of well-differentiated lesions, and more estrogen receptor (ER)-positive tumors. Patients with MBC had significantly higher 5 and10-year CSS rates (98.23 and 96.03%, respectively) than patients with IDC (91.44 and 85.48%, respectively). Univariate and multivariate analyses showed that MBC was an independent factor for better prognosis. As for patients with MBC, the event of death caused by another disease exceeded the event of death caused by breast cancer. A competing risk regression model further showed that lymph node involvement, poorly differentiated grade and advanced T-classification were independent factors of poor prognosis in patients with MBC. The Nomogram can accurately predict CSS with a high C-index (0.816). Risk scores developed from the nomogram can more accurately predict the prognosis of patients with MBC (C-index = 0.789) than the traditional TNM system (C-index = 0.704, P< 0.001). Conclusions: Patients with MBC have a better prognosis than patients with IDC. Nomograms could help clinicians make more informed decisions in clinical practice. The competing risk regression model, as a more rational model, is recommended for use in the survival analysis of patients with MBC in the future. [ABSTRACT FROM AUTHOR]

Purpose: Leptin dysregulation has been postulated to affect cancer risk through its effects on obesity and inflammation. Epidemiological data evaluating this relationship are conflicting and studies in non-white cohorts is lacking. Therefore, we examined the association of leptin with the risk of incident cancer in the multiethnic Dallas Heart Study (DHS). Methods: Participants enrolled in the DHS without prevalent cancer and with baseline leptin measurements were included. Incident cancer cases were identified through a systematic linkage of the DHS and the Texas Cancer Registry. Leptin was evaluated both as a continuous variable and in sex-specific quartiles. Multivariable Cox proportional hazards modeling was performed to examine the association between leptin levels with incident cancer after adjusting for age, sex, race, smoking status, alcohol use, family history of malignancy, body mass index (BMI), diabetes mellitus and C-reactive protein. Results: Among 2,919 participants (median age 44 years; 54% women; 70% nonwhite; median BMI 29.4 kg/m2), 190 (6.5%) developed cancer after median follow- up of 12 years. Median leptin levels were 12.9 (interquartile range [IQR] 5.8–29.5) ng/ml in the incident cancer group vs. 12.3 (IQR 5.4–26.4) ng/ml those without an incident cancer (p = 0.34). Leptin was not associated with cancer incidence in multivariable analysis (unit standard deviation increase in log-transformed leptin, hazard ratio 0.95; 95% confidence interval, 0.77–1.16; p = 0.60). No association was observed in analyses stratified by sex, race/ethnicity, diabetes, or obesity status. Conclusions: In this study of a predominantly minority population, no association between premorbid leptin levels and cancer incidence was demonstrated. Despite preclinical rationale and positive findings in other studies, this association may not replicate across all racial/ethnic populations. [ABSTRACT FROM AUTHOR]

Gastric adenocarcinoma, a single heterogeneous disease with multiple epidemiological and histopathological characteristics, accounts for approximately 10% of cancers worldwide. It is categorized into four histological types: papillary adenocarcinoma (PAC), tubular adenocarcinoma (TAC), mucinous adenocarcinoma (MAC), and signet ring cell adenocarcinoma (SRC). Effective differentiation of the four types of adenocarcinoma will greatly improve the treatment of gastric adenocarcinoma to increase its five-year survival rate. We reported here the differentiation of the four histological types of gastric adenocarcinoma from the molecularly structural viewpoint of confocal Raman microspectroscopy. In total, 79 patients underwent laparoscopic or open radical gastrectomy during 2008–2011: 21 for signet ring cell carcinoma, 21 for tubular adenocarcinoma, 14 for papillary adenocarcinoma, 6 for mucinous carcinoma, and 17 for normal gastric mucosas obtained from patients underwent operation for other benign lesions. Clinical data were retrospectively reviewed from medical charts, and Raman data were processed and analyzed by using principal component analysis (PCA) and linear discriminant analysis (LDA). Two-dimensional plots of PCA and LDA clearly demonstrated that the four histological types of gastric adenocarcinoma could be differentiated, and confocal Raman microspectroscopy provides potentially a rapid and effective method for differentiating SRC and MAC from TAC or PAC. [ABSTRACT FROM AUTHOR]

Objective: Radiation therapy (RT) for esophageal cancer often results in unintended radiation doses delivered to the heart owing to anatomic proximity. Using the Surveillance, Epidemiology, and End Results (SEER) database, we examined late cardiac death in survivors of esophageal cancer that had or had not received RT. Methods: 5,630 patients were identified that were diagnosed with esophageal squamous cell carcinoma (SCC) or adenocarcinoma (AC) from 1973–2012, who were followed for at least 5 years after therapy. Examined risk factors for cardiac death included age (≤55/56-65/66-75/>75), gender, race (white/non-white), stage (local/regional/distant), histology (SCC/AC), esophageal location (<18cm/18-24cm/25-32cm/33-40cm from incisors), diagnosis year (1973-1992/1993-2002/2003-2012), and receipt of surgery and/or RT. Time to cardiac death was evaluated using the Kaplan-Meier method. A Cox model was used to evaluate risk factors for cardiac death in propensity score matched data. Results: Patients who received RT were younger, diagnosed more recently, had more advanced disease, SCC histology, and no surgery. The RT group had higher risk of cardiac death than the no-RT group (log-rank p<0.0001). The median time to cardiac death in the RT group was 289 months (95% CI, 255–367) and was not reached in the no-RT group. The probability of cardiac death increased with age and decreased with diagnosis year, and this trend was more pronounced in the RT group. Multivariate analysis found RT to be associated with higher probability of cardiac death (OR 1.23, 95% CI 1.03–1.47, HR 1.961, 95% CI 1.466–2.624). Lower esophageal subsite (33–40 cm) was also associated with a higher risk of cardiac death. Other variables were not associated with cardiac death. Conclusions: Recognizing the limitations of a SEER analysis including lack of comorbidity accountability, these data should prompt more definitive study as to whether a possible associative effect of RT on cardiac death could potentially be a causative effect. [ABSTRACT FROM AUTHOR]

Unplanned excision of extremity soft tissue sarcoma (STS) is common and has detrimental effects not only on patients’ oncologic outcomes but also on functional and economic issues. However, no study has analyzed a nationwide population-based database. To estimate the incidence and treatment pattern of unplanned excision in extremity STS in the Korean population, a nationwide epidemiologic study was performed using the Korean Health Insurance Review and Assessment Service database, a centralized nationwide healthcare claims registry of Korea that covers the entire Korean population. Among 1,517 patients with extremity STS in the 4-year study period, 553 (36.5%) underwent unplanned excision (unplanned group). About 80% of unplanned excisions were performed in tertiary or general hospitals. Of the unplanned group, 240 (43.4%) underwent re-excision with or without radiation therapy and/or chemotherapy, and 51 (9.2%) did not undergo re-excision but were treated with radiation therapy and/or chemotherapy; whereas, 262 (47.4%) did not undergo any further treatment following unplanned excision. This study is the first nationwide population-based study on the unplanned excision of extremity STS. The results may have implications in establishing preventive or therapeutic measures to reduce the burden of unplanned excision of extremity STS. [ABSTRACT FROM AUTHOR]

Background: Pancreatic cancer has poor prognosis and existing interventions provide a modest benefit. Statin has anti-cancer properties that might enhance survival in pancreatic cancer patients. We sought to determine whether statin treatment after cancer diagnosis is associated with longer survival in those with pancreatic ductal adenocarcinoma (PDAC). Methods: We analyzed data on 7813 elderly patients with PDAC using the linked Surveillance, Epidemiology, and End Results (SEER) - Medicare claims files. Information on the type, intensity and duration of statin use after cancer diagnosis was extracted from Medicare Part D. We treated statin as a time-dependent variable in a Cox regression model to determine the association with overall survival adjusting for follow-up, age, sex, race, neighborhood income, stage, grade, tumor size, pancreatectomy, chemotherapy, radiation, obesity, dyslipidemia, diabetes, chronic pancreatitis and chronic obstructive pulmonary disease (COPD). Results: Overall, statin use after cancer diagnosis was not significantly associated with survival when all PDAC patients were considered (HR = 0.94, 95%CI 0.89, 1.01). However, statin use after cancer diagnosis was associated with a 21% reduced hazard of death (Hazard ratio = 0.79, 95% confidence interval (CI) 0.67, 0.93) in those with grade I or II PDAC and to a similar extent in those who had undergone a pancreatectomy, in those with chronic pancreatitis and in those who had not been treated with statin prior to cancer diagnosis. Conclusions: We found that statin treatment after cancer diagnosis is associated with enhanced survival in patients with low-grade, resectable PDAC. [ABSTRACT FROM AUTHOR]

Aberrant epigenetic events contribute to tumorigenesis of all human cancers. Significant efforts are underway in developing new generation of epigenetic cancer therapeutics. Although clinical trials for agents targeting DNA hypermethylation and histone deacetylation have yielded promising results, developing agents that target histone methylation remains to be in the early stage. We and others have previously reported that 3-Deazaneplanocin A (DZNep) is a histone methylation inhibitor that has a wide range of anticancer effects in various human cancers. Here, focusing on acute myeloid leukemia (AML) as a model, we reported a less toxic analog of DZNep, named D9, which is shown to be efficacious in AML cell lines and patient-derived samples in vitro, as well as AML tumorigenesis in vivo. Gene expression analysis in a panel of AML cell lines treated with D9 identified a set of genes that is associated with D9 sensitivity and implicated in multiple oncogenic signaling pathways. Moreover, we show that D9 is able to deplete the leukemia stem cells (LSC) and abolish chemotherapy-induced LSC enrichment, leading to dramatic elimination of AML cell survival. Thus, D9 appears to be a robust epigenetic compound that may constitute a potential for AML therapy. [ABSTRACT FROM AUTHOR]

Background: Several meta-analyses confirmed the five most prevalent human papillomavirus (HPV) strains in women with and without cervical neoplastic diseases are HPV16, 18, 31, 52, and 58. HPV16/18 are the predominant oncogenic genotypes, causing approximately 70% of global cervical cancer cases. The vast majority of the women studied in previous analyses were from Europe, North America, Asia, and most recently Latin America and the Caribbean. Despite the high burden of cervical cancer morbidity and mortality in Africa, a robust meta-analysis of HPV genotype prevalence and distribution in African women is lacking. Methods and Findings: We systematically searched 14 major databases from inception to August 2013 without language restriction, following the Meta-Analysis of Observational Studies in Epidemiology and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Seventy-one studies from 23 African countries were identified after screening 1162 citations and data abstracted and study quality appraised from 195 articles. HPV type-specific prevalence and distribution was estimated from 17,273 cases of women with normal cervical cytology; 1019 women with atypical squamous cells of undetermined significance (ASCUS); 1444 women with low-grade squamous intraepithelial lesion (LSIL); 1571 women with high-grade squamous intraepithelial lesion (HSIL); and 4,067 cases of invasive cervical carcinoma (ICC). Overall prevalence of HPV16/18 were 4.4% and 2.8% of women with normal cytology, 12.0% and 4.4% with ASCUS, 14.5% and 10.0% with LSIL, 31.2% and 13.9% with HSIL, and 49.7% and 18.0% with ICC, respectively. Study limitations include the lack of adequate data from Middle and Northern African regions, and variations in the HPV type-specific sensitivity of different genotyping protocols. Conclusions: To our knowledge, this study is the most comprehensive assessment of the overall prevalence and distribution of HPV genotypes in African women with and without different cervical neoplasias. We have established that HPV16/18 account for 67.7% of ICC cases among African women. Based on our findings, we highly recommend the administration of existing prophylactic vaccines to younger women not infected with HPV16/18 and an increase in HPV screening efforts for high-risk genotypes to prevent cervical cancer. Review registration: International Prospective Register of Systematic Reviews CRD42013006558. [ABSTRACT FROM AUTHOR]

The prediction of space radiation induced cancer risk carries large uncertainties with two of the largest uncertainties being radiation quality and dose-rate effects. In risk models the ratio of the quality factor (QF) to the dose and dose-rate reduction effectiveness factor (DDREF) parameter is used to scale organ doses for cosmic ray proton and high charge and energy (HZE) particles to a hazard rate for γ-rays derived from human epidemiology data. In previous work, particle track structure concepts were used to formulate a space radiation QF function that is dependent on particle charge number Z, and kinetic energy per atomic mass unit, E. QF uncertainties where represented by subjective probability distribution functions (PDF) for the three QF parameters that described its maximum value and shape parameters for Z and E dependences. Here I report on an analysis of a maximum QF parameter and its uncertainty using mouse tumor induction data. Because experimental data for risks at low doses of γ-rays are highly uncertain which impacts estimates of maximum values of relative biological effectiveness (RBEmax), I developed an alternate QF model, denoted QFγAcute where QFs are defined relative to higher acute γ-ray doses (0.5 to 3 Gy). The alternate model reduces the dependence of risk projections on the DDREF, however a DDREF is still needed for risk estimates for high-energy protons and other primary or secondary sparsely ionizing space radiation components. Risk projections (upper confidence levels (CL)) for space missions show a reduction of about 40% (CL∼50%) using the QFγAcute model compared the QFs based on RBEmax and about 25% (CL∼35%) compared to previous estimates. In addition, I discuss how a possible qualitative difference leading to increased tumor lethality for HZE particles compared to low LET radiation and background tumors remains a large uncertainty in risk estimates. [ABSTRACT FROM AUTHOR]

Background: Malignant ameloblastoma, comprising metastasizing ameloblastoma and ameloblastic carcinoma, represents 1.6–2.2% of all odontogenic tumors. Due to its rare nature, malignant ameloblastoma has only been reported in the literature in small case series or case reports. Using the Surveillance, Epidemiology and End-Results (SEER) database, we have performed a population-based study to determine the incidence rate and the absolute survival of malignant ameloblastoma. Method: Using the International Classification of Diseases for Oncology (ICD-O) codes 9310/3 and 9270/3, data from the SEER database were used to calculate the incidence rate and absolute survival rate of population with malignant ameloblastoma. Results: The overall incidence rate of malignant ameloblastoma was 1.79 per 10 million person/year. The incidence rate was higher in males than females and also higher in black versus white population. The median overall survival was 17.6 years from the time of diagnosis and increasing age was associated with a statistically significant poorer survival. Conclusions: To our best knowledge, we report the largest population-based series of malignant ameloblastoma. The incidence rate was 1.79 per 10 million person/year and the overall survival was 17.6 years. [ABSTRACT FROM AUTHOR]

Background: Accumulated evidence has indicated that ataxia-telangiectasia mutated (ATM) gene polymorphisms are closely related to lung cancer. We aimed to explore the prognostic value of rs189037 (G>A), one of ATM single nucleotide polymorphisms (SNPs), and detect whether it involves in the risk of lung cancer in Chinese Han people. Methods: In this hospital-based matched case-control study, 852 lung cancer patients and 852 healthy controls have been put into comparison to analyze the association between rs189037 and lung cancer risk in Chinese. The single nucleotide polymorphisms were determined by TaqMan real-time PCR and we used SPSS software to perform the statistical analyses. Results: Individuals carrying variant AA genotype of rs189037 had higher lung cancer risk (adjusted OR: 1.56) than those carrying GG genotype. After analyzing data respectively from different groups divided by genders and smoking status, we observed that the risk effect of AA genotype on the lung cancer was significant in females, non-smokers and female non-smokers, as well as the risk effect of GA genotype in male smokers. Compared with non-smokers carrying GG genotype, smokers carrying at least one A allele had higher risk of developing lung cancer than those with GG genotype (adjusted OR: 3.52 vs. adjusted OR: 2.53). Conclusions: This study suggested that rs189037 (G>A) polymorphism is associated with lung cancer risk in Chinese Han population. AA genotype and A allele may be dangerous lung cancer signals in Chinese and make contribution to diagnostic and treatment value. [ABSTRACT FROM AUTHOR]

Background: Data on survival with mucosal melanoma and on prognostic factors of are scarce. It is still unclear if the disease course allows for mucosal melanoma to be treated as primary cutaneous melanoma or if differences in overall survival patterns require adapted therapeutic approaches. Furthermore, this investigation is the first to present 10-year survival rates for mucosal melanomas of different anatomical localizations. Methodology: 116 cases from Sep 10 1984 until Feb 15 2011 retrieved from the Comprehensive Cancer Center and of the Central Register of the German Dermatologic Society databases in Tübingen were included in our analysis. We recorded anatomical location and tumor thickness, and estimated overall survival at 2, 5 and 10 years and the mean overall survival time. Survival times were analyzed with the Kaplan-Meier method. The log-rank test was used to compare survival times by localizations and by T-stages. Principal Findings: We found a median overall survival time of 80.9 months, with an overall 2-year survival of 71.7%, 5-year survival of 55.8% and 10-year survival of 38.3%. The 10-year survival rates for patients with T1, T2, T3 or T4 stage tumors were 100.0%, 77.9%, 66.3% and 10.6% respectively. 10-year survival of patients with melanomas of the vulva was 64.5% in comparison to 22.3% of patients with non-vulva mucosal melanomas. Conclusion: Survival times differed significantly between patients with melanomas of the vulva compared to the rest (p = 0.0006). It also depends on T-stage at the time of diagnosis (p<0.0001). [ABSTRACT FROM AUTHOR]

Background: Several prospective cohort and case-control studies reported the inconsistent association between biospecimen composition of C20 and C22 long-chain (LC) n-3 polyunsaturated fatty acid (PUFA) and colorectal cancer (CRC) risk. The aim of the present study was to investigate the association of biospecimen LC n-3 PUFA with CRC risk based on prospective cohort and case-control studies. Methods and Results: Cochrane Library, PubMed, and EMBASE database were searched up to February 2014 for eligible studies. Risk ratios (RRs) or odds ratios (ORs) from prospective and case-control studies were combined using a random-effects model in the highest vs. lowest categorical analysis. Nonlinear dose-response relationships were assessed using restricted cubic spline regression models. Difference in tissue composition of LC n-3 PUFA between cases and noncases was analyzed as standardized mean difference (SMD). Three prospective cohort studies and 8 case-control studies were included in the present study, comprising 60,627 participants (1,499 CRC cases and 59,128 noncases). Higher biospecimen LC n-3 PUFA was significantly associated with a lower risk of CRC in case-control (pooled OR: 0.76; 95% CI: 0.59, 0.97; I2 = 10.00%) and prospective cohort studies (pooled RR: 0.70; 95% CI: 0.55, 0.88; I2 = 0.00%), respectively. A significant dose-response association was found of biospecimen C20:5n-3 (P for nonlinearity  = 0.02) and C22:6n-3 (P for trend  = 0.01) with CRC risk, respectively. Subjects without CRC have significantly higher biospecimen compositions of C20:5n-3 (SMD: 0.27; 95%: 0.13, 0.41), C22:6n-3 (SMD: 0.23; 95%: 0.11, 0.34) and total LC n-3 PUFA (SMD: 0.22; 95% CI: 0.07, 0.37) compared with those with CRC. Conclusions: The present evidence suggests human tissue compositions of LC n-3 PUFA may be an independent predictive factor for CRC risk, especially C20:5n-3 and C22:6n-3. This needs to be confirmed with more large-scale prospective cohort studies. [ABSTRACT FROM AUTHOR]

Aim: To assess the association between excess body weight and cancer risk in patients with type 2 diabetes (T2D) who were registered in the Swedish National Diabetes Register (NDR). Methods: This is a cohort study based on 25,268 patients with T2D and baseline BMI≥18.5 kg/m2 from NDR 1997–1999. Subjects were grouped according to BMI into normal weight (18.5 to 24.9), overweight (25 to 29.9) or obesity (30 or more). All subjects were followed until the first occurrence of cancer, or death, or the end of follow-up (December 31, 2009). Adjusted hazard ratios (HRs) and 95% confidence interval (CI) for cancer risks were estimated by Cox regression. Results: In men with T2D, overweight was associated with increased risks of all cancer [1.13 (1.02–1.27)], gastrointestinal cancer [1.34 (1.07–1.72)] and colorectal cancer [1.59 (1.18–2.13)]; obesity was related to higher risks of all cancer [1.17 (1.04–1.33)], gastrointestinal cancer [1.40 (1.08–1.82)] and colorectal cancer [1.62 (1.17–2.24)]. In women with T2D, obesity was associated with increased risk of all cancer [1.30 (1.12–1.51)], gastrointestinal cancer [1.40 (1.03–1.91)] and postmenopausal breast cancer [1.39 (1.00–1.91)]. Conclusions: Excess body weight was associated with increased risks of all cancer, gastrointestinal cancer and colorectal cancer in men with T2D. Obesity was related with elevated risks of all cancer, gestational cancer and postmenopausal breast cancer in women with T2D. [ABSTRACT FROM AUTHOR]

Background: Current prophylactic vaccines against human papillomavirus (HPV) target two of the most oncogenic types, HPV-16 and -18, which contribute to roughly 70% of cervical cancers worldwide. Second-generation HPV vaccines include a 9-valent vaccine, which targets five additional oncogenic HPV types (i.e., 31, 33, 45, 52, and 58) that contribute to another 15–30% of cervical cancer cases. The objective of this study was to determine a range of vaccine costs for which the 9-valent vaccine would be cost-effective in comparison to the current vaccines in two less developed countries (i.e., Kenya and Uganda). Methods and Findings: The analysis was performed using a natural history disease simulation model of HPV and cervical cancer. The mathematical model simulates individual women from an early age and tracks health events and resource use as they transition through clinically-relevant health states over their lifetime. Epidemiological data on HPV prevalence and cancer incidence were used to adapt the model to Kenya and Uganda. Health benefit, or effectiveness, from HPV vaccination was measured in terms of life expectancy, and costs were measured in international dollars (I$). The incremental cost of the 9-valent vaccine included the added cost of the vaccine counterbalanced by costs averted from additional cancer cases prevented. All future costs and health benefits were discounted at an annual rate of 3% in the base case analysis. We conducted sensitivity analyses to investigate how infection with multiple HPV types, unidentifiable HPV types in cancer cases, and cross-protection against non-vaccine types could affect the potential cost range of the 9-valent vaccine. In the base case analysis in Kenya, we found that vaccination with the 9-valent vaccine was very cost-effective (i.e., had an incremental cost-effectiveness ratio below per-capita GDP), compared to the current vaccines provided the added cost of the 9-valent vaccine did not exceed I$9.7 per vaccinated girl. To be considered very cost-effective, the added cost per vaccinated girl could go up to I$5.2 and I$16.2 in the worst-case and best-case scenarios, respectively. At a willingness-to-pay threshold of three times per-capita GDP where the 9-valent vaccine would be considered cost-effective, the thresholds of added costs associated with the 9-valent vaccine were I$27.3, I$14.5 and I$45.3 per vaccinated girl for the base case, worst-case and best-case scenarios, respectively. In Uganda, vaccination with the 9-valent vaccine was very cost-effective when the added cost of the 9-valent vaccine did not exceed I$8.3 per vaccinated girl. To be considered very cost-effective, the added cost per vaccinated girl could go up to I$4.5 and I$13.7 in the worst-case and best-case scenarios, respectively. At a willingness-to-pay threshold of three times per-capita GDP, the thresholds of added costs associated with the 9-valent vaccine were I$23.4, I$12.6 and I$38.4 per vaccinated girl for the base case, worst-case and best-case scenarios, respectively. Conclusions: This study provides a threshold range of incremental costs associated with the 9-valent HPV vaccine that would make it a cost-effective intervention in comparison to currently available HPV vaccines in Kenya and Uganda. These prices represent a 71% and 61% increase over the price offered to the GAVI Alliance ($5 per dose) for the currently available 2- and 4-valent vaccines in Kenya and Uganda, respectively. Despite evidence of cost-effectiveness, critical challenges around affordability and feasibility of HPV vaccination and other competing needs in low-resource settings such as Kenya and Uganda remain. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer is common cancer. Discovering novel genetic biomarkers might help to identify high-risk individuals. Copy number variation (CNV) has recently been shown to influence risk for several cancers. The aim of the present study was sought to test the association between copy number at a variant region and GC. Methods: A total of 110 gastric cancer patients and 325 healthy volunteers were enrolled in this study. We searched for a CNV and found a CNV (Variation 7468) containing part of the APC gene, the SRP19 gene and the REEP5 gene. We chose four probes targeting at APC-intron8, APC-exon9, SRP19 and REEP5 to interrogate this CNV. Specific Taqman probes labeled by different reporter fluorophores were used in a real-time PCR platform to obtain copy number. Both the original non-integer data and transformed integer data on copy number were used for analyses. Results: Gastric caner patients had a lower non-integer copy number than controls for the APC-exon9 probe (Adjusted p = 0.026) and SRP19 probe (Adjusted p = 0.002). The analysis of integer copy number yielded a similar pattern although less significant (Adjusted p = 0.07 for APC-exon9 probe and Adjusted p = 0.02 for SRP19 probe). Conclusions: Losses of a CNV at 5q22, especially in the DNA region surrounding APC-exon 9, may be associated with a higher risk of gastric cancer. [ABSTRACT FROM AUTHOR]

As a heterogeneous kind of malignances, Non-Hodgkin lymphoma (NHL) is the most common hematologic cancer worldwide with the significantly increased morbidity in China. Accumulated evidences demonstrated that oncoprotein MDM4 plays a crucial role in the TP53 tumor suppressor signaling pathway. An rs4245739 A>C polymorphism locating in the MDM4 3′-untranslated region creates a miR-191 target site and results in allele-specific MDM4 expression. In this study, we examined the association between this polymorphism as well as the TP53 Arg72Pro (rs1042522 G>C) genetic variant and Non-Hodgkin Lymphoma (NHL) risk in a Chinese Han population. Genotypes were determined in 200 NHL cases and 400 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression. We found significantly increased NHL risk among carriers of the TP53 72Pro allele compared with those with the 72Arg allele (P = 0.002 for the Pro/Pro genotype). We also observed a significantly decreased NHL risks among carriers of the MDM4 rs4245739 C allele compared with those with the A allele in Chinese (P = 0.014 for the AC genotype). Stratified analyses revealed the associations between these SNPs and NHL risk are especially noteworthy in young or male individuals. Additionally, the associations are much pronounced in NHL patients with B-cell lymphomas or grade 3 or 4 disease. Our results indicate that the TP53 Arg72Pro and the MDM4 rs4245739 polymorphisms contribute to NHL susceptibility and support the hypothesis that genetic variants in the TP53 pathway genes can act as important modifiers of NHL risk. [ABSTRACT FROM AUTHOR]

Introduction: There is a need to assess risk of second primary cancers in prostate cancer (PCa) patients, especially since PCa treatment may be associated with increased risk of second primary tumours. Methods: We calculated standardized incidence ratios (SIRs) for second primary tumours comparing men diagnosed with PCa between 1980 and 2010 in the Canton of Zurich, Switzerland (n = 20,559), and the general male population in the Canton. Results: A total of 1,718 men developed a second primary tumour after PCa diagnosis, with lung and colon cancer being the most common (15 and 13% respectively). The SIR for overall second primary cancer was 1.11 (95%CI: 1.06–1.17). Site-specific SIRs varied from 1.19 (1.05–1.34) to 2.89 (2.62–4.77) for lung and thyroid cancer, respectively. When stratified by treatment, the highest SIR was observed for thyroid cancer (3.57 (1.30–7.76)) when undergoing surgery, whereas liver cancer was common when treated with radiotherapy (3.21 (1.54–5.90)) and kidney bladder was most prevalent for those on hormonal treatment (3.15 (1.93–4.87)). Stratification by time since PCa diagnosis showed a lower risk of cancer for men with PCa compared to the general population for the first four years, but then a steep increase in risk was observed. Conclusion: In the Canton of Zurich, there was an increased risk of second primary cancers among men with PCa compared to the general population. Increased diagnostic activity after PCa diagnosis may partly explain increased risks within the first years of diagnosis, but time-stratified analyses indicated that increased risks remained and even increased over time. [ABSTRACT FROM AUTHOR]

Background: Mounting evidence from experimental and animal studies suggests that vitamin A may have a protective effect on melanoma, but the findings on the association of vitamin A intake with risk of melanoma have been inconsistently reported in epidemiologic studies. We attempted to elucidate the association by performing a meta-analysis. Methods: Eligible studies were identified by searching PubMed and EMBASE databases, as well as by reviewing the references of retrieved publications. Summary odds ratios (OR) with corresponding 95% confidence interval (CI) were computed with a random-effects model. Study-specific ORs and 95% CIs for the highest vs. lowest categories of vitamin A intake were pooled. Results: A total of 8 case-control studies and 2 prospective studies comprising 3,328 melanoma cases and 233,295 non-case subjects were included. The summary OR for the highest compared with the lowest intake of total vitamin A, retinol and beta-carotene was 0.86 (95% CI = 0.59–1.25), 0.80 (95% CI = 0.69–0.92) and 0.87 (95%CI = 0.62–1.20), respectively. Significant heterogeneity was observed among studies on vitamin A and beta-carotene intake, but not among studies on retinol intake. Subgroup and sensitivity analyses confirmed these findings. There was no indication of publication bias. Conclusion: Findings from this meta-analysis suggest that intake of retinol, rather than of total vitamin A or beta-carotene, is significantly associated with reduced risk of melanoma. [ABSTRACT FROM AUTHOR]

African American patients with colorectal cancer show higher mortality than their Caucasian counterparts. Biology might play a partial role, and prior studies suggest a higher prevalence for microsatellite instability (MSI) among cancers from African Americans, albeit patients with MSI cancers have improved survival over patients with non-MSI cancers, counter to the outcome observed for African American patients. CD8+ T cell infiltration of colon cancer is postively correlated with MSI tumors, and is also related to improved outcome. Here, we utilized a 503-person, population-based colon cancer cohort comprising 45% African Americans to determine, under blinded conditions from all epidemiological data, the prevalence of MSI and associated CD8+ T cell infiltration within the cancers. Among Caucasian cancers, 14% were MSI, whereas African American cancers demonstrated 7% MSI (P = 0.009). Clinically, MSI cancers between races were similar; among microsatellite stable cancers, African American patients were younger, female, and with proximal cancers. CD8+ T cells were higher in MSI cancers (88.0 vs 30.4/hpf, P<0.0001), but was not different between races. Utilizing this population-based cohort, African American cancers show half the MSI prevalence of Caucasians without change in CD8+ T cell infiltration which may contribute towards their higher mortality from colon cancer. [ABSTRACT FROM AUTHOR]

Background: In colon cancer patients, obesity, sedentary lifestyle, and high dietary glycemic load have been associated with increased risk of cancer recurrence. High sugar-sweetened beverage intake has been associated with obesity, diabetes, and cardio-metabolic diseases, but the influence on colon cancer survival is unknown. Methods: We assessed the association between sugar-sweetened beverage consumption on cancer recurrence and mortality in 1,011 stage III colon cancer patients who completed food frequency questionnaires as part of a U.S. National Cancer Institute-sponsored adjuvant chemotherapy trial. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated with Cox proportional hazard models. Results: Patients consuming ≥2 servings of sugar-sweetened beverages per day experienced an adjusted HR for disease recurrence or mortality of 1.67 (95% CI, 1.04–2.68), compared with those consuming <2 servings per month (Ptrend = 0.02). The association of sugar-sweetened beverages on cancer recurrence or mortality appeared greater among patients who were both overweight (body mass index ≥25 kg/m2) and less physically active (metabolic equivalent task-hours per week <18) (HR = 2.22; 95% CI, 1.29–3.81, Ptrend = 0.0025). Conclusion: Higher sugar-sweetened beverage intake was associated with a significantly increased risk of cancer recurrence and mortality in stage III colon cancer patients. [ABSTRACT FROM AUTHOR]

Background: In recent years, some reports have suggested that papillary thyroid cancers are more frequently associated with lymphocytic thyroiditis or Hashimoto's thyroiditis. This study investigated a potential increase in the prevalence of chronic lymphocytic thyroiditis among papillary thyroid cancer patients. Materials and Methods: We used national epidemiological survey data on thyroid cancer patients diagnosed in 1999, 2005, and 2008. A retrospective medical record survey was conducted by representative sampling of a national cancer incidence database. The analysis included 5,378 papillary thyroid cancer patients aged 20–79 years. We calculated the age-standardized prevalence and age-adjusted prevalence ratios using a binomial regression model with a log link for the prevalence of chronic lymphocytic thyroiditis among papillary thyroid cancer patients by sex for each year. Results: The prevalence of chronic lymphocytic thyroiditis among papillary thyroid cancer patients was 4.0% and 12.8% for men and women in 1999, 6.5% and 24.6% in 2005, and 10.7% and 27.6% in 2008, respectively. Between 1999 and 2008, the age-standardized prevalence of chronic lymphocytic thyroiditis increased 4.1-fold in male patients and 2.0-fold in female patients with papillary thyroid cancer. The prevalence of other thyroid diseases, however, did not increase in either gender. Conclusions: Among Korean papillary thyroid cancer patients, the prevalence of chronic lymphocytic thyroiditis increased between 1999 and 2008, whereas the prevalence of other thyroid disorders did not change. [ABSTRACT FROM AUTHOR]

Purpose: We assessed the accuracy of communication between doctors and patients by evaluating the consistency between patient perception of cancer stage and the medical records, and analyzed the most influential factors of incongruence among cancer patients at 10 cancer centers across Korea. Methods: Information was gathered from cancer patients at the National Cancer Center and nine regional cancer centers located in every province of Korea between 1 July 2008 and 31 August 2008. Data were analyzed using Pearson's χ2 test and multivariate logistic regression analysis. Results: The stages of cancer reported by the 1,854 patients showed a low degree of congruence with the stages given in medical records (k = 0.35, P<0.001). Only 57.1% of the patients had accurate knowledge of their cancer stage. In total, 18.5% underestimated their stage of disease, and the more advanced the cancer stage, the more likely they were to underestimate it, in order of local (14.2%), regional (23.7%), and distant (51.6%). Logistic regression analysis showed that congruence was lower in patients with cervical cancer (odds ratio [OR] = 0.51, 95% confidence interval [CI] = 0.30–0.87), recurrence (OR = 0.64, 95% CI = 0.50–0.83), and treatment at the National Cancer Center (OR = 0.53, 95% CI = 0.39–0.72). Conclusion: There are knowledge gaps between patients' perceived and actual stage of cancer. Patients with cervical cancer, recurrence, and who received treatment at a regional cancer center showed less understanding of their cancer stage. [ABSTRACT FROM AUTHOR]

Background: Reduced overall survival has been observed in patients with left-sided versus right-sided breast cancer due to cardiac toxicity after radiotherapy. However, the effect of laterality and primary tumor site on breast cancer-specific mortality (BCSM) remains unclear. Patients and Methods: We analyzed data from 305,443 women ages 20- to 79-years-old diagnosed with breast cancer between 1990 and 2009. The data were obtained from the population-based Surveillance, Epidemiology, and End Results (SEER) program of the U.S. National Cancer Institute. The survival outcomes with regard to laterality and primary tumor site were compared using univariate and multivariate (Cox proportional hazards regression model) methods. Results: In the multivariate analysis, BCSM was affected by the primary tumor site (P<0.0001) but not laterality (P = 0.331). The combined effect was piecewise: using the left upper-outer quadrant as the reference, the BCSM hazard ratio (HR) was not significant in the right upper quadrant (P = 0.755) and the right central portion (P = 0.329). The BCSM HR was slightly increased in the left central portion as well as the left and right lower-outer quadrants (HRs from 1.136 to 1.145; P<0.0001). The BCSM HR was significantly increased in the upper-inner and lower-inner quadrants (HRs from 1.242 to 1.372; P<0.0001) on both sides. Laterality only impacted BCSM in patients with breast cancer located in the central portion (HR, 1.100; P = 0.013, using the right side as the reference). Conclusion: Patients with tumors in the upper-outer quadrant of both sides and the right central portion have a better prognosis than patients with tumors at other locations. Laterality is not regarded as a prognostic factor in breast cancer. [ABSTRACT FROM AUTHOR]

Angioimmunoblastic T-cell lymphoma (AITL) is a rare lymphoid malignancy with dismal prognosis. We conducted a large population-based study using the Surveillance, Epidemiology, and End Results (SEER) database (1973–2010) to determine the temporal survival trends and prognostic factors of AITL patients. A total of 1207 patients with AITL were included in this study, with a median age at diagnosis of 69 years. At presentation, most patients (79.5%) had an advanced-stage disease. Overall survival (OS) probabilities at 2, 5 and 10 years were 46.8%, 32.9%, and 21.9% respectively. Two-year, 5-year, and 10-year disease-specific survival (DSS) rates were 56.1%, 44.0%, and 35.9% respectively.On multivariate analysis, age older than 70 years, advanced-stage disease and male sex were identified adverse predictors for OS and DSS. We failed to find any survival differences among subgroups diagnosed in the 5 periods studied (1992 to 1998, 1999 to 2001, 2002 to 2004, 2005 to 2007, and 2008 to 2010). The current study represents the largest specific series of patients with AITL and the first investigation on temporal changes in survival of AITL patients. There has been no survival improvement for AITL patients over the past two decades. Further investigations are warranted to develop more effective treatment for AITL. [ABSTRACT FROM AUTHOR]

Background: Hypermethylation of the suppressor of cytokine signaling 3(SOCS3) promoter has been reported to predict a poor prognosis in several cancers including glioblstoma multiforme (GBM). We explored the function of SOCS3 promoter hypermethylation in GBM cohorts, including analysis of the CpG island methylator phenotype (CIMP), when a large number of gene loci are simultaneously hypermethylated. Methods: A whole genome promoter methylation profile was performed in a cohort of 33 GBM samples, with 13 long-term survivors (LTS; overall survival ≥ 18 months) and 20 short-term survivors (STS; overall survival ≤ 9 months). The SOCS3 promoter methylation status was compared between the two groups. In addition, we investigated the relationship of SOCS3 promoter methylation and G-CIMP status. Results: Interestingly, in our present study, we found that SOCS3 promoter methylation was statistically significantly higher in the 13 LTS than that in the 20 STS. Furthermore, high SOCS3 promoter methylation detected via pyro-sequencing predicted a better prognosis in an independent cohort containing 62 GBM patients. This correlation was validated by the dataset from the Cancer Genome Atlas(TCGA) and the Chinese Cancer Genome Atlas(CGGA). In addition, we found that hypermethylation of the SOCS3 promoter was tightly associated with the G-CIMP-positive GBM patients. Conclusions: Using a total of 359 clinical samples, we demonstrate that SOCS3 promoter hypermethylation status has a favorable prognostic value in GBM patients because of whole genome methylation status. Particularly, the hypermethylation of the SOCS3 promoter indicates positive G-CIMP status. [ABSTRACT FROM AUTHOR]

Objectives: multiple myeloma is a malignant neoplasm of plasma cells mainly affecting elderly patients. Despite the wealth of information available on therapeutic strategies, the etiology and pathogenesis of myeloma remain unclear. In the current study, a meta-analysis was conducted to assess the possible association between rheumatoid arthritis and myeloma. Methods: a literature search was conducted with PubMed, EMBASE and Web of Science for relevant studies published by December 25, 2013. Additionally, we searched annual meeting abstracts of the American Society of Hematology from 2004 to 2013. Only original studies that investigated the association between rheumatoid arthritis and myeloma were included. In total, 8 case-control and 10 cohort studies were identified for analysis. Results: the meta-estimate of the association between rheumatoid arthritis and myeloma was 1.14 (95% CI, 0.97–1.33) overall, with significant heterogeneity among studies. The relationship between myeloma and other autoimmune diseases was additionally examined from available data. Our results showed that myeloma risk is increased 1.31 to 1.65-fold in pernicious anemia and 1.36 to 2.30-fold in ankylosing spondylitis patients. Conclusion: Rheumatoid arthritis does not appear to alter the risk of myeloma, while between-study heterogeneity analyses suggest caution in the interpretation of results. Pernicious anemia and ankylosing spondylitis may be potential risk factors for myeloma development. Future large-scale epidemiological studies with reliable exposure biomarkers are necessary to establish the possible contribution of autoimmune disorders to multiple myeloma. [ABSTRACT FROM AUTHOR]

Background and Objectives: Studies of the association between excess body weight and risk of meningioma have produced inconsistent results. Therefore, a meta-analysis of published studies was performed to better assess the association between meningioma and excess body weight. Methods: A literature search was conducted in the PubMed and EMBASE databases without any limitations. The reference lists of identified articles were also screened for additional studies. The summary relative risks (RRs) and 95% confidence intervals (CI) were calculated using fixed- or random-effects models. Results: A total of 6 studies provided risk estimates for overweight or obesity. Overall, the combined RRs were 1.12 (95% CI = 0.98–1.28) for overweight and 1.45 (95% CI = 1.26–1.67) for obesity. After stratification by gender, no significant association was observed for obese men (RR = 1.30, 95% CI = 0.64–2.62), while significant association was detected for obese women (RR = 1.46, 95% CI = 1.26–1.69). No substantial differences emerged across strata of study design and geographic areas. Conclusion: The results of this meta-analysis suggest that obesity but not overweight is associated with an increased risk of meningioma. Due to the limited number of studies, further research is needed to confirm the association. [ABSTRACT FROM AUTHOR]

Background: Cervical cancer is the third largest cause of cancer mortality in India. The objectives of the study were to compare the pre and the post treatment quality of life in cervical cancer patients and to develop a prediction model to provide an insight into the possibilities in the treatment modules. Methodology/Principal Findings: A total of 198 patients were assessed with two structured questionnaires of Health Related Quality of Life (The European Organisation for Research and Treatment of Cancer, EORTC QLQ C-30 and CX-24). The baseline observations were recorded when the patients first reported (T1) and second evaluation was done at 6 months post treatment (T2). The mean age of detection was 50.9 years with the literacy level being non-educated or less than high school. Majority of them were married/cohabiting 179 (90.4%). On histopathological examination (HPE) squamous cell carcinoma was found to be the most common cell type carcinoma 147 (74.2%) followed by Adenocarcinoma 31 (15.7%). Radical hysterectomy was the most common treatment modality 76 (38.4%), followed by Wertheims Hysterectomy 46 (23.2%) and Radiochemotherapy 59 (29.8%). The mean score of global health of cervical cancer patients post treatment was 77.90, which was significantly higher than the pre - treatment score (54.32). Mean “symptoms score” post treatment was 21.69 with an aggravation of 7.32 compared to pre treatment scores. Patients experienced substantial decrease in sexual activity post treatment. Conclusions/Significance: The prediction model(PrediQt-Cx), based on Support Vector Machine(SVM) for predicting post treatment HRQoL in cervical cancer patients was developed and internally cross validated. After external validation PrediQt-Cx can be easily employed to support decision making by clinicians and patients from north India region, through openly made available for access at http://prediqt.org. [ABSTRACT FROM AUTHOR]

Purpose: Rab27a belongs to the Rab small GTPase superfamily. The protein is membrane-bound and may be involved in protein transport and small GTPase-mediated signal transduction. Mutations in this gene are associated with Griscelli syndrome type 2. However, the prognostic and molecular features of gliomas with Rab27a expression are still unclear. Experimental Design: We used a whole-genome mRNA expression microarray dataset of 220 glioma samples from the Chinese Glioma Genome Atlas (CGGA) database (http://www.cgga.org.cn) as a discovery set. In this set, 220 gliomas, consisting of 97 WHO Grade II gliomas, 34 WHO Grade III gliomas, and 89 WHO Grade IV gliomas, were analyzed using the Kaplan-Meier method. To validate the protein expression of Rab27a, we assayed another 162 glioma samples by immunohistochemistry. Three additional datasets were obtained as validation sets. Gene ontology (GO) analysis and gene set variation analysis (GSVA) were used for the functional annotation of Rab27a in 89 WHO Grade IV gliomas. Results: Rab27a was significantly associated with grade progression and high mortality in all grades of glioma in the discovery set. Rab27a also showed a mesenchymal subtype, G3 subtype and isocitrate dehydrogenase 1 (IDH1) wild-type preference and association with migration. The 3 validation datasets revealed similar findings. Rab27a was more highly expressed in gliomas than in normal brain tissues, and its expression increased with glioma grade progression. Conclusions: Rab27a expression was significantly associated with grade progression and worse prognosis in all grades of gliomas, suggesting Rab27a as a novel biomarker with potentially important therapeutic implications. [ABSTRACT FROM AUTHOR]