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Background: The association of body composition with epithelial ovarian carcinoma (EOC) mortality is poorly understood. To date, evidence suggests that high adiposity is associated with decreased mortality (an obesity paradox), but the impact of muscle on this association has not been investigated. Herein, we define associations of muscle and adiposity joint-exposure body composition phenotypes with EOC mortality., Methods: Body composition from 500 women in the Body Composition and Epithelial Ovarian Cancer Survival Study was dichotomized as normal or low skeletal muscle index (SMI), a proxy for sarcopenia, and high or low adiposity. Four phenotypes were classified as fit (normal SMI and low adiposity; reference; 16.2%), overweight or obese (normal SMI and high adiposity; 51.2%), sarcopenia and overweight or obese (low SMI and high adiposity; 15.6%), and sarcopenia or cachexia (low SMI and low adiposity; 17%). We used multivariable Cox models to estimate associations of each phenotype with mortality for EOC overall and high-grade serous ovarian carcinoma (HGSOC)., Results: Overweight or obesity was associated with up to 51% and 104% increased mortality in EOC and HGSOC [Hazard Ratio (HR)] = 1.51, 95% CI = 1.05 to 2.19 and HR = 2.04, 95% CI = 1.29 to 3.21). Sarcopenia and overweight or obesity was associated with up to 66% and 67% increased mortality in EOC and HGSOC (HR = 1.66, 95% CI = 1.13 to 2.45 and HR = 1.67, 95% CI = 1.05 to 2.68). Sarcopenia or cachexia was associated with up to 73% and 109% increased mortality in EOC and HGSOC (HR = 1.73, 95% CI = 1.14 to 2.63 and HR = 2.09, 95% CI = 1.25 to 3.50)., Conclusions: Overweight or obesity, sarcopenia and overweight or obesity, and sarcopenia or cachexia phenotypes were each associated with increased mortality in EOC and HGSOC. Exercise and dietary interventions could be leveraged as ancillary treatment strategies for improving outcomes in the most fatal gynecological malignancy with no previously established modifiable prognostic factors., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Tubo-ovarian high-grade serous carcinomas (HGSC) are highly proliferative neoplasms that generally respond well to platinum/taxane chemotherapy. We recently identified minichromosome maintenance complex component 3 (MCM3), which is involved in the initiation of DNA replication and proliferation, as a favorable prognostic marker in HGSC. Our objective was to further validate whether MCM3 mRNA expression and possibly MCM3 protein levels are associated with survival in patients with HGSC. MCM3 mRNA expression was measured using NanoString expression profiling on formalin-fixed and paraffin-embedded tissue (N = 2355 HGSC) and MCM3 protein expression was assessed by immunohistochemistry (N = 522 HGSC) and compared with Ki-67. Kaplan-Meier curves and the Cox proportional hazards model were used to estimate associations with survival. Among chemotherapy-naïve HGSC, higher MCM3 mRNA expression (one standard deviation increase in the score) was associated with longer overall survival (HR = 0.87, 95% CI 0.81-0.92, p < 0.0001, N = 1840) in multivariable analysis. MCM3 mRNA expression was highest in the HGSC C5.PRO molecular subtype, although no interaction was observed between MCM3, survival and molecular subtypes. MCM3 and Ki-67 protein levels were significantly lower after exposure to neoadjuvant chemotherapy compared to chemotherapy-naïve tumors: 37.0% versus 46.4% and 22.9% versus 34.2%, respectively. Among chemotherapy-naïve HGSC, high MCM3 protein levels were also associated with significantly longer disease-specific survival (HR = 0.52, 95% CI 0.36-0.74, p = 0.0003, N = 392) compared to cases with low MCM3 protein levels in multivariable analysis. MCM3 immunohistochemistry is a promising surrogate marker of proliferation in HGSC., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Problem: Previous studies identified circulating CD14 + HLA-DR lo/- monocytic cells as an immune suppressive subset in solid malignancies, such as prostate, renal cell carcinoma, and pancreatic cancer. Such monocytic cells have been implicated not only in tumour progression but also as a potential barrier for immunotherapy. This study examined the relationship between the frequency of circulating monocytic cells and epithelial ovarian cancer (EOC) progression pre- and post-frontline chemotherapy, defined by disease stage, which is a leading prognostic factor for this malignancy., Method of Study: Incident cases of 236 women with EOC were recruited and comprehensive flow cytometry was utilized to assess the frequency of peripheral blood CD33 + CD11b + HLA-DR -/low CD14 + CD15 - monocytic cells, henceforth termed CD14 + HLA-DR lo/- monocytic cells, prior to and after completion of frontline chemotherapy. Multivariable odds ratios (OR) were used to estimate the association between CD14 + HLA-DR lo/- monocytic cell percentages and disease stage. Wilcoxon signed-rank tests evaluated changes in these monocytic cell levels pre- and post-chemotherapy in a patient subset (n = 70)., Results: Patients with elevated frequencies of circulating CD14 + HLA-DR lo/- monocytic cells at diagnosis were at 3.33-fold greater odds of having advanced stage (III/IV) EOC (CI: 1.04-10.64), with a significant trend in increasing CD14 + HLA-DR lo/- monocytic cell levels (P = .04). There was a 2.02% median decrease of these monocytic cells post-chemotherapy among a subset of patients with advanced stage disease (P < .0001)., Conclusion: These findings support the potential clinical relevance of CD14 + HLA-DR lo/- monocytic cells in EOC for prognosis and may indicate a non-invasive biomarker to measure disease progression., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: This study was performed to examine the association between adulthood recreational physical inactivity (PIA) and mortality among patients with cancers of the head and neck., Methods: Patients with head and neck cancer at Roswell Park between years 1990 to 1998 were included (N = 305). Multivariable Cox proportional hazard ratios (HR) with corresponding 95% confidence intervals (CI) were used to analyze the association between PIA and risk of dying., Results: There was a 1.40-fold increase in risk of dying among PIA patients, when compared to active patients with head and neck cancers (HR = 1.40, CI: 1.03-1.91). This was observed greater in PIA women (HR = 2.40, CI: 1.28-4.52), patients who were overweight/obese (HR = 1.76, CI: 1.09-2.85), patients with pharynx as the primary site (HR = 1.85, CI: 1.01-3.38), and patients with distant metastasis (HR = 5.19, CI: 1.37-19.65)., Conclusion: Physically inactive patients with head and neck cancers are at significantly greater risk of dying when compared to patients who are active., (© 2020 Wiley Periodicals, Inc.)

Objective: To determine the association between pre-diagnostic recreational physical inactivity (RPI) and pancreatic cancer (PC) mortality., Methods: This analysis included 107 patients seen at Roswell Park Comprehensive Cancer Center diagnosed with PC between 1989 and 1998. Cox proportional hazards models were used to determine hazard ratios (HR) and 95% confidence intervals (CI) for PC mortality associated with self-reported pre-diagnostic RPI. Models were adjusted for known prognostic factors, including age, sex, stage at diagnosis, smoking status, and body mass index (BMI). Results were also stratified by sex, BMI, smoking status, histology, and treatment status., Results: We observed a significant association between RPI and PC mortality in all patients (HR = 1.72, 95% CI = 1.06-2.79), as well as among overweight or obese patients (HR = 2.74, 95% 95% CI = 1.42-5.29), females (HR = 2.63; 95% CI, 1.08-6.39), and non-smokers (HR = 1.72; 95% CI, 1.02-2.89)., Conclusion: These results suggest that RPI prior to PC diagnosis is associated with a higher risk of death. Future studies with larger sample sizes are needed to explore whether this association varies across tumor histology.

We recently reported evidence that a strong, BRCA-independent locus on the X-chromosome may contribute to ovarian cancer predisposition in families ascertained from the Familial Ovarian Cancer Registry (Buffalo, NY, USA). While it has been estimated that approximately 20% of all ovarian cancer cases are hereditary, it is possible that a significant proportion of cases previously believed to be sporadic may, in fact, be X-linked. Such X-linked disease has a distinct pattern; it implies that a father will necessarily pass a risk allele to each of his daughters, increasing the prevalence of cancers clustered within a family. X-chromosome inactivation further influences the expression of X-linked alleles and may represent a novel target for screening and therapy. Herein, we review the current literature regarding X-linked ovarian cancer and interpret allele transmission-based models to characterize X-linked ovarian cancer and develop a framework for clinical and epidemiological familial ascertainment to inform the design of future studies., Competing Interests: The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Primary ovarian mucinous tumors can be difficult to distinguish from metastatic gastrointestinal neoplasms by histology alone. The expected immunoprofile of a suspected metastatic lower gastrointestinal tumor is CK7 - /CK20 + /CDX2 + /PAX8 - . This study assesses the addition of a novel marker SATB2, to improve the diagnostic algorithm. A test cohort included 155 ovarian mucinous tumors (105 carcinomas and 50 borderline tumors) and 230 primary lower gastrointestinal neoplasms (123 colorectal adenocarcinomas and 107 appendiceal neoplasms). All cases were assessed for SATB2, PAX8 CK7, CK20, and CDX2 expression on tissue microarrays. Expression was scored in a 3-tier system as absent, focal (1-50% of tumor cells) and diffuse ( >50% of tumor cells) and then categorized into either absent/present or nondiffuse/diffuse. SATB2 and PAX8 expression was further evaluated in ovarian tumors from an international cohort of 2876 patients (expansion cohort, including 159 mucinous carcinomas and 46 borderline mucinous tumors). The highest accuracy of an individual marker in distinguishing lower gastrointestinal from ovarian mucinous tumors was CK7 (91.7%, nondiffuse/diffuse cut-off) followed by SATB2 (88.8%, present/absent cut-off). The most effective combination was CK7 and SATB2 with accuracy of 95.3% using the 3-tier interpretation, absent/focal/diffuse. This combination outperformed the standard clinical set of CK7, CK20 and CDX2 (87.5%). Re-evaluation of outlier cases confirmed ovarian origin for all but one case. The accuracy of SATB2 was confirmed in the expansion cohort (91.5%). SATB2 expression was also detected in 15% of ovarian endometrioid carcinoma but less than 5% of other ovarian histotypes. A simple two marker combination of CK7 and SATB2 can distinguish lower gastrointestinal from ovarian primary mucinous tumors with greater than 95% accuracy. PAX8 and CDX2 have value as second-line markers. The utility of CK20 in this setting is low and this warrants replacement of this marker with SATB2 in clinical practice.

An association between genetic variants in the vitamin D receptor (VDR) gene and epithelial ovarian cancer (EOC) was previously reported in women of African ancestry (AA). We sought to examine associations between genetic variants in VDR and additional genes from vitamin D biosynthesis and pathway targets (EGFR, UGT1A, UGT2A1/2, UGT2B, CYP3A4/5, CYP2R1, CYP27B1, CYP24A1, CYP11A1, and GC). Genotyping was performed using the custom-designed 533,631 SNP Illumina OncoArray with imputation to the 1,000 Genomes Phase 3 v5 reference set in 755 EOC cases, including 537 high-grade serous (HGSOC), and 1,235 controls. All subjects are of African ancestry (AA). Logistic regression was performed to estimate odds ratios (OR) and 95% confidence intervals (CI). We further evaluated statistical significance of selected SNPs using the Bayesian False Discovery Probability (BFDP). A significant association with EOC was identified in the UGT2A1/2 region for the SNP rs10017134 (per allele OR = 1.4, 95% CI = 1.2-1.7, P = 1.2 × 10 -6 , BFDP = 0.02); and an association with HGSOC was identified in the EGFR region for the SNP rs114972508 (per allele OR = 2.3, 95% CI = 1.6-3.4, P = 1.6 × 10 -5 , BFDP = 0.29) and in the UGT2A1/2 region again for rs1017134 (per allele OR = 1.4, 95% CI = 1.2-1.7, P = 2.3 × 10 -5 , BFDP = 0.23). Genetic variants in the EGFR and UGT2A1/2 may increase susceptibility of EOC in AA women. Future studies to validate these findings are warranted. Alterations in EGFR and UGT2A1/2 could perturb enzyme efficacy, proliferation in ovaries, impact and mark susceptibility to EOC., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objective: We aimed to investigate the prognostic impact of duration of first-line chemotherapy administration in patients with epithelial ovarian cancer (EOC)., Methods: Chemotherapy records were abstracted from the electronic medical record. Patients with on-time completion (105 days) were compared to patients finishing early (<105 days), delays of 1-4 weeks, or >4 weeks. For 222 women with stage IIIC/IV, stage-stratified estimates of progression-free survival (PFS) and overall survival (OS) were compared. A delay sub-study was performed with outliers removed. Each week of delay was correlated with the change in PFS and OS to identify time points associated with change in outcome., Results: Most women had on-time completion of chemotherapy (23.6%) or a treatment delay of ≤4 weeks (21.8%); 21.6% of women experienced a delay longer than 4 weeks. R0 resection at initial debulking (OR = 1.99, 95%CI: 1.18-3.36, p = 0.010) and RECIST complete response (OR = 4.88, 95%CI: 2.47-10.63, p<0.001) were strongly associated with on-time completion. Patients with on-time completion and < 1 month delay had similar median survivals of 43.1 months (lower 95% CI bound 33.7 months) and 44.5 months (lower bound 37.0, p = 0.93). Women with >1 month delay had decreased median survival of 18.1 months (14.7-24.9 months), while women with short intervals survived 35.0 months (95%CI: 21.8-49.8 months). Short-term delays lead to progressively decreasing OS. This was significantly different from the on-schedule survival estimate after 6 weeks of delay., Conclusions: On-time completion of chemotherapy correlates with increased survival and higher complete response rates. Increasing delays in chemotherapy completion were associated with decreased survival., Competing Interests: The authors have declared that no competing interests exist.

Background: Although physical activity is a well-established risk factor for several cancer types, studies evaluating its association with lymphoma have yielded inconclusive results. In such cases where physical activity is not clearly associated with cancer risk in a dose-dependent manner, investigators have begun examining physical inactivity as an independent exposure of interest., Methods: Associations of self-reported, lifetime physical inactivity with risk of developing Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) were evaluated in a hospital-based case control study using data from the Patient Epidemiology Data System at Roswell Park Comprehensive Cancer Center. Participants included 87 patients with HL and 236 patients with NHL as well as 348 and 952 cancer-free controls, respectively. Multivariable-adjusted logistic regression models were fit to calculate odds ratios (OR) and 95% confidence intervals (CI) estimating the association between physical inactivity and lymphoma risk., Results: We observed significant, positive associations between lifetime recreational physical inactivity and risk of both HL (OR = 1.90, 95% CI: 1.15-3.15) and NHL (OR = 1.35, 95% CI: 1.01-1.82)., Conclusions: The current analysis provides evidence for a positive association between physical inactivity and risk of both HL and NHL. These results add to a growing body of research suggesting that lifetime physical inactivity may be an important independent, modifiable behavioral risk factor for cancer., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Although family history of testicular cancer is well-established as a risk factor for testicular cancer, it is unknown whether family history of ovarian cancer is associated with risk of testicular cancer., Materials and Methods: Using data from the Familial Ovarian Cancer Registry on 2636 families with multiple cases of ovarian cancer, we systematically compared relative frequencies of ovarian cancer among relatives of men with testicular and non-testicular cancers., Results: Thirty-one families with cases of both ovarian and testicular cancer were identified. We observed that, among men with cancer, those with testicular cancer were more likely to have a mother with ovarian cancer than those with non-testicular cancers (OR = 3.32, p = 0.004). Zero paternal grandmothers of men with testicular cancer had ovarian cancer., Conclusion: These observations provide compelling preliminary evidence for a familial association between ovarian and testicular cancers Future studies should be designed to further investigate this association and evaluate X-linkage., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Given prior evidence that an affected woman conveys a higher risk of ovarian cancer to her sister than to her mother, we hypothesized that there exists an X-linked variant evidenced by transmission to a woman from her paternal grandmother via her father. We ascertained 3,499 grandmother/granddaughter pairs from the Familial Ovarian Cancer Registry at the Roswell Park Cancer Institute observing 892 informative pairs with 157 affected granddaughters. We performed germline X-chromosome exome sequencing on 186 women with ovarian cancer from the registry. The rate of cancers was 28.4% in paternal grandmother/granddaughter pairs and 13.9% in maternal pairs consistent with an X-linked dominant model (Chi-square test X2 = 0.02, p = 0.89) and inconsistent with an autosomal dominant model (X2 = 20.4, p<0.001). Paternal grandmother cases had an earlier age-of-onset versus maternal cases (hazard ratio HR = 1.59, 95%CI: 1.12-2.25) independent of BRCA1/2 status. Reinforcing the X-linked hypothesis, we observed an association between prostate cancer in men and ovarian cancer in his mother and daughters (odds ratio, OR = 2.34, p = 0.034). Unaffected mothers with affected daughters produced significantly more daughters than sons (ratio = 1.96, p<0.005). We performed exome sequencing in reported BRCA negative cases from the registry. Considering age-of-onset, one missense variant (rs176026 in MAGEC3) reached chromosome-wide significance (Hazard ratio HR = 2.85, 95%CI: 1.75-4.65) advancing the age of onset by 6.7 years. In addition to the well-known contribution of BRCA, we demonstrate that a genetic locus on the X-chromosome contributes to ovarian cancer risk. An X-linked pattern of inheritance has implications for genetic risk stratification. Women with an affected paternal grandmother and sisters of affected women are at increased risk for ovarian cancer. Further work is required to validate this variant and to characterize carrier families.

Purpose: Multiple studies have examined the role of anthropometric characteristics in ovarian cancer risk and survival; however, their results have been conflicting. We investigated the associations between weight change, height and height change and risk and outcome of ovarian cancer using data from a large population-based case-control study., Methods: Data from 699 ovarian cancer cases and 1,802 controls who participated in the HOPE study were included. We used unconditional logistic regression adjusted for age, race, number of pregnancies, use of oral contraceptives, and family history of breast or ovarian cancer to examine the associations between self-reported height and weight and height change with ovarian cancer risk. Cox proportional hazards regression models adjusted for age and stage were used to examine the association between the exposure variables and overall and progression-free survival among ovarian cancer cases., Results: We observed an increased risk of ovarian cancer mortality and progression for gaining more than 20 pounds between ages 18-30, HR 1.36; 95% CI 1.05-1.76, and HR 1.31; 95% CI 1.04-1.66, respectively. Losing weight and gaining it back multiple times was inversely associated with both ovarian cancer risk, OR 0.78; 95% CI 0.63-0.97 for 1-4 times and OR 0.73; 95% CI 0.54-0.99 for 5-9 times, and mortality, HR 0.63; 95% CI 0.40-0.99 for 10-14 times. Finally, being taller during adolescence and adulthood was associated with increased risk of mortality. Taller stature and weight gain over lifetime were not related to ovarian cancer risk., Conclusions: Our results suggest that height and weight and their change over time may influence ovarian cancer risk and survival. These findings suggest that biological mechanisms underlying these associations may be hormone driven and may play an important role in relation to ovarian carcinogenesis and tumor progression.

Introduction: Investigations of the independent associations of physical inactivity with cancer endpoints have been mounting in the epidemiological literature, in part due to the high prevalence of physical inactivity among cancer patients and to evidence that inactivity associates with carcinogenesis via pathways independent of obesity. Yet, physical inactivity is not currently recognized as a well-established risk or prognostic factor for lung cancer. As such, we examined the associations of lifetime physical inactivity with lung cancer risk and mortality in a hospital-based, case-control study., Presentation of Case: Materials and Methods: The analyses included data from 660 lung cancer patients and 1335 matched cancer-free controls. Multivariable logistic regression analyses were utilized to assess the association between lifetime physical inactivity and lung cancer risk, and Cox proportional hazards models were utilized to estimate the association between lifetime physical inactivity and mortality among lung cancer cases. Results: We observed a significant positive association between lifetime physical inactivity and lung cancer risk: [Odds ratio (OR)=2.23, 95% confidence interval (CI): 1.77-2.81]; the association remained significant among never smokers (OR=3.00, 95% CI:1.33-6.78) and non-smokers (OR=2.33, 95% CI: 1.79-3.02). We also observed a significant positive association between lifetime physical inactivity and lung cancer mortality [Hazard ratio (HR)=1.40, 95% CI: 1.14-1.71]; the association remained significant in non-smokers (HR=1.51, 95% CI: 1.16-1.95)., Discussion/conclusion: These data add to the body of evidence suggesting that physical inactivity is an independent risk and prognostic factor for cancer. Additional research utilizing prospectively collected data is needed to substantiate the current findings., Competing Interests: Conflicts of Interest: None

Despite mounting epidemiological evidence suggesting an inverse association between recreational physical activity and cancer risk, evidence associated with head and neck cancer is scant. We conducted a case-control analysis to examine the associations of lifetime physical inactivity with the risk of head and neck squamous cell carcinoma (HNSCC). We utilized data from the Patient Epidemiology Data System at Roswell Park Cancer Institute (RPCI). Participants included 246 patients with HNSCC and 504 cancer-free controls who received medical services at RPCI between 1990 and 1998. Participants were considered physically inactive if they did not participate in any regular, weekly recreational physical activity throughout their lifetime, prior to diagnosis. Multivariate logistic regression models were utilized to estimate odds ratios (OR) and 95% confidence intervals (CI) representing the association between lifetime physical inactivity and HNSCC risk. We observed a significant positive association between recreational physical inactivity and HNSCC risk (OR = 2.73, 95% CI 1.87-3.99, p < 0.001). In subgroup analyses by body mass index (BMI) (underweight/normal-weight: OR = 3.40, 95% CI 1.89-6.12, p < 0.001; overweight/obese: OR = 2.40, 95% CI 1.43-4.02, p < 0.001) and smoking status (former smoker: OR = 3.12, 95% CI 1.89-5.14, p < 0.001; never smoker: OR = 2.71, 95% CI 1.21-6.05, p = 0.020; current smoker: OR = 1.61, 95% CI 0.66-3.95, p = 0.300), significant positive associations were also observed. Results of the current analyses suggest that lifetime physical inactivity associates with HNSCC independent of BMI. In addition, physical inactivity may be a modifiable risk factor among never smokers. These data add to the growing body of evidence suggesting that physical inactivity may be an independent risk factor for cancer.

Background: Findings from in vitro studies suggest that increased exposure to thyroid hormones can influence progression of ovarian tumours. However, epidemiologic evidence on this topic is limited., Methods: We pooled data from 11 studies from the Ovarian Cancer Association Consortium. Using multivariate Cox proportional hazards models, we estimated associations between hyper- and hypothyroidism and medications prescribed for these conditions with 5-year all-cause survival among women diagnosed with invasive ovarian cancer., Results: Overall, there was a nonsignificant association with history of hyperthyroidism (n=160 cases) and mortality (HR=1.22; 95% CI=0.97-1.53). Furthermore, diagnosis of hyperthyroidism within the 5 years before ovarian cancer diagnosis was associated with an increased risk of death (HR=1.94; 95% CI=1.19-3.18). A more modest association was observed with history of hypothyroidism (n=624 cases) and mortality (HR=1.16; 95% CI=1.03-1.31). Neither duration of hypothyroidism nor use of thyroid medications was associated with survival., Conclusions: In this large study of women with ovarian cancer, we found that recent history of hyperthyroidism and overall history of hypothyroidism were associated with worse 5-year survival.

Objectives: Recreational physical inactivity has been gaining recognition as an independent epidemiological exposure of interest in relation to cancer endpoints due to evidence suggesting that it may associate with cancer independent of obesity. In the current analyses, we examined the associations of lifetime recreational physical inactivity with renal and bladder cancer risk., Methods: In this hospital-based case-control study, we identified N=160 renal cancer patients, N=208 bladder cancer patients, and N=766 age frequency-matched controls without cancer. Participants self-reporting never participating in any regular/weekly recreational physical activity throughout their lifetime were classified as physically inactive. Utilizing unconditional multivariable logistic regression analyses, we estimated odds ratios and 95% confidence intervals to represent the associations between lifetime physical inactivity and renal and bladder cancer risk., Results: In multivariable logistic regression models, we observed significant positive associations between lifetime recreational physical inactivity and renal cancer and bladder cancer risk: odds ratio=1.77 (95% CI: 1.10-2.85) and odds ratio=1.73 (95% CI: 1.13-2.63), respectively. Similar associations also persisted among individuals who were not obese for both renal and bladder cancer: odds ratio=1.75 (95% CI: 1.03-2.98) and odds ratio=1.70 (95% CI: 1.08-2.69), respectively., Conclusions: In this case-control study, we observed evidence of a positive association between renal and bladder cancer with lifetime recreational physical inactivity. These data add to the growing body of evidence suggesting that physical inactivity may be an important independent risk factor for cancer. However, additional studies using a larger sample and prospectively collected data are needed to substantiate the current findings., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: The precise mechanism by which the immune system is adversely affected in cancer patients remains poorly understood, but the accumulation of immunosuppressive/protumorigenic myeloid-derived suppressor cells (MDSCs) is thought to be a prominent mechanism contributing to immunologic tolerance of malignant cells in epithelial ovarian cancer (EOC). To this end, we hypothesized genetic variation in MDSC pathway genes would be associated with survival after EOC diagnoses. Methods: We measured the hazard of death due to EOC within 10 years of diagnosis, overall and by invasive subtype, attributable to SNPs in 24 genes relevant in the MDSC pathway in 10,751 women diagnosed with invasive EOC. Versatile Gene-based Association Study and the admixture likelihood method were used to test gene and pathway associations with survival. Results: We did not identify individual SNPs that were significantly associated with survival after correction for multiple testing ( P < 3.5 × 10 -5 ), nor did we identify significant associations between the MDSC pathway overall, or the 24 individual genes and EOC survival. Conclusions: In this well-powered analysis, we observed no evidence that inherited variations in MDSC-associated SNPs, individual genes, or the collective genetic pathway contributed to EOC survival outcomes. Impact: Common inherited variation in genes relevant to MDSCs was not associated with survival in women diagnosed with invasive EOC. Cancer Epidemiol Biomarkers Prev; 26(3); 420-4. ©2016 AACR ., (©2016 American Association for Cancer Research.)

Background/Aim: Appendiceal mucinous neoplasms (AMNs) are tumors with dysplastic mucinous epithelium, a pushing growth pattern but no infiltrative invasion to the appendiceal wall. Some AMNs are associated with pseudomyxoma peritonei, characterized by intraperitoneal mucinous involvement. Recent studies have demonstrated that LAMNs confined to the appendix have low or no risk for disease recurrence, progression, and peritoneal involvement during follow up. Case Report: Here, we present two extremely rare cases with confined low grade appendiceal mucinous neoplasm (pTis and pT3) and simultaneous extraperitoneal subcutaneous or ovary involvement at the time of diagnosis. Conclusion: Our cases demonstrate that although the primary tumor is limited to the appendix, coexisting distant metastasis may occur on very rare occasions. [ABSTRACT FROM AUTHOR]

BACKGROUND: Living in neighborhoods with higher levels of walkability has been associated with a reduced risk of obesity and higher levels of physical activity. Obesity has been linked to increased risk of 13 cancers in women. However, long-term prospective studies of neighborhood walkability and risk for obesity-related cancer are scarce. OBJECTIVES: We evaluated the association between long-term average neighborhood walkability and obesity-related cancer risk in women. METHODS: The New York University Women’s Health Study (NYUWHS) is a prospective cohort with 14,274 women recruited between 1985 and 1991 in New York City and followed over nearly three decades. We geocoded residential addresses for each participant throughout follow-up and calculated an average annual measure of neighborhood walkability across years of follow-up using data on population density and accessibility to destinations associated with geocoded residential addresses. We used ICD-9 codes to characterize first primary obesity-related cancers and employed Cox proportional hazards models to assess the association between average neighborhood walkability and risk of overall and site-specific obesity-related cancers. RESULTS: Residing in neighborhoods with a higher walkability level was associated with a reduced risk of overall and site-specific obesity-related cancers. The hazards ratios associated with a 1-standard deviation increase in average annual neighborhood walkability were 0.88 (95% CI: 0.85, 0.93) for overall obesity-related cancer, 0.89 (95% CI: 0.84, 0.95) for postmenopausal breast cancer, 0.82 (95% CI: 0.68, 0.99) for ovarian cancer, 0.87 (95% CI: 0.76, 0.99) for endometrial cancer, and 0.68 (95% CI: 0.49, 0.94) for multiple myeloma, adjusting for potential confounders at both the individual and neighborhood level. The association between neighborhood walkability and risk of overall obesity-related cancer was stronger among women living in neighborhoods with higher levels of poverty compared with women living in areas with lower poverty levels (푝Interaction = 0.006). DISCUSSION: Our study highlights a potential protective role of neighborhood walkability in preventing obesity-related cancers in women. [ABSTRACT FROM AUTHOR]

Objectives: To determine the relationship between chemotherapy dose delay/reduction with progression-free survival (PFS) and overall survival (OS) in colorectal cancer patients treated with FOLFIRI based first-line chemotherapy in real-world retrospectively study. Methods: We identified 144 eligible patients with advanced CRC who received FOLFIRI as first-line based treatment. The study protocol was submitted to the institutional review board and was exempted. Dose delay was defined as an average delay of more than 3 days (>3 days vs. =3 days) from the intended date. Dose reduction (actual dose/standard dose = 100%) =85% was considered as chemotherapy reduction in the chemotherapy dose relative to the standard (mg/m2) regimen for all cycles. Relative dose intensity (RDI) =80% was described as chemotherapy reduction. OS and PFS were measured using Kaplan-Meier and Cox proportional hazard models. Results: There were 114 patients with chemotherapy dose delay (dose delay >3 days). PFS of patients without dose delay had better survival than patients with dose delay (p = 0.002). There were 28.47% patients treated with dose reduction of 5-Fu. PFS and OS were better in patients without 5-Fu dose reduction than in patients with 5-Fu dose reduction with p values of 0.024 and <0.001, respectively. Patients with high 5-FU RDI had better PFS than patients with low 5-FU RDI (p < 0.001). While, there was no statistical difference in OS between the two groups. Then we stratified the analysis by age. In <65 years cohort, both PFS and OS were better in patients with high 5-Fu RDI than in those with low 5-Fu RDI (p < 0.001, p = 0.005, respectively). But, in =65 years cohort, OS were better in patients with low 5-Fu RDI than in those with high 5-Fu RDI (p = 0.025). Moreover, both dose reduction and RDI of irinotecan had no statistically significant difference in both PFS and OS. Conclusion: In the advanced colorectal cancer patients who received FOLFIRI based treatment as first-line regimen, chemotherapy dose delay and reduction dose of 5-Fu were associated with worse survival, especially among patients younger than 65 years. [ABSTRACT FROM AUTHOR]

Purpose: Cigarette smoking is an established risk factor for bladder cancer (BC), but evidence for physical inactivity and obesity is limited. Methods: This analysis included 146,027 participants from the Cancer Prevention Study-II (CPS-II) Nutrition Cohort, a large prospective cohort of cancer incidence established in 1992. Multivariable-adjusted Cox proportional hazards models were used to examine associations between body mass index (BMI), moderate-to-vigorous intensity aerobic physical activity (MVPA), leisure-time spent sitting, and BC risk. Effect modification by stage, smoking status, and sex was examined. Results: Only participants accumulating 15.0- < 30.0 MET-hrs/wk of MVPA had a lower risk of BC overall (RR 0.88, 95% CI 0.78, 0.99, compared to > 0–7.5 MET-hrs/wk) in the fully adjusted models. When stratifying on BC stage, MVPA (15- < 30 MET-hrs/wk vs. > 0- < 7.5 MET-hrs/wk, RR 0.83, 95% CI 0.70–0.99) and excess sitting time (≥ 6 h/day vs. 0- < 3 h/day RR 1.22, 95% CI 1.02, 1.47) were associated with risk of invasive BC only. There was no consistent evidence for effect modification by smoking status or sex. Conclusion: This study supports that MVPA and sitting time may play a role in BC incidence, but associations likely differ by stage at diagnosis. While additional studies are needed to confirm associations by stage, this study adds to the evidence of the importance of being physically active for cancer prevention. [ABSTRACT FROM AUTHOR]

Purpose: Testicular cancer is frequently seen, especially in young males, and constitutes 1% of all male cancers. Family history, testicular dysgenesis syndrome, and the presence of tumour in the contralateral testis are each well-defined epidemiological risk factors. The aim of the current study was to determine the distribution of these risk factors according to tumour stage and to evaluate the effects on progression. Materials and methods: A total of 71 patients diagnosed with testicular cancer in our clinic between January 2018 and December 2021 were classified according to tumour stage (Group 1: Early, n = 29; Group 2: Advanced, n = 42). The presence of risk factors, and demographic and pathological data were recorded. Results: No significant difference was determined between the groups in respect of age, comorbidities, and tumour type (p > 0.05). There was no difference between Group 1 and Group 2 in terms of median follow-up time [15.5 (17.5), 16.5(26.5) months, respectively, p = 0.4]. Epidemiological risk factors were seen more in Group 2 than in Group 1 (p = 0.03). Progression-free survival was determined to be shorter in patients with risk factors compared to those without (7.95 ± 1.3 vs. 29.4 ± 2.06 months, p < 0.001, respectively). Family history and testicular dysgenesis syndrome were determined to be independent risk factors for progression [HR:0.046 (0.004–0.485); HR:0.101 (0.03–0.347), p < 0.05, respectively]. Conclusions: More advanced-stage tumours are seen in patients with testicular cancer when epidemiological risk factors are also present. Of these risk factors, family history and testicular dysgenesis syndrome have a negative effect on progression. [ABSTRACT FROM AUTHOR]

Upper aerodigestive tract (UADT) malignancies account for significant proportion of all malignancies. The aim of the study is to know the demography and patterns of tobacco consumption and the proportion of non-tobacco consumers in patients with UADT carcinoma. Patient diagnosed with primary UADT carcinoma visiting outpatient department in a tertiary centre from February 2009 to May 2011 were included in the study. 150 patients were documented with UADT carcinoma and analysed. Among these 133 were males and 17 were female. 40% of them had smoking, 25% had smokeless tobacco, 13% had both smoking and smokeless tobacco and 22% hadn't had any form of tobacco. Carcinoma larynx is the most common site and glottis is the commonest subsite. Most individuals who developed UADT carcinoma have used tobacco in some form. The high proportion of UADT carcinoma in non-tobacco consumer is alarming. [ABSTRACT FROM AUTHOR]

Hematological malignancies including leukemia, multiple myeloma, and lymphoma are known as leading causes of death around the world. Despite all developments in cancer management, current therapeutic methods are still relatively inefficient, leading to the heavy financial burdens for public health systems. Strategic attempts in clinical practice must be based on three serious goals including (1) increasing the efficacy of treatments and decreasing their side‐effects; (2) decreasing financial price of treatments and related morbidity and mortality rates; and (3) improving life quality and survival of affected patients. Melatonin, a multipotential neurohormone mainly secreted by the pineal gland, has recently been shown to play essential roles in the treatment of various human diseases. Moreover, it possesses anticancer impacts and acts through regulation of underlying cellular and molecular mechanisms. In this article, we review mechanistic roles and beneficial effects of melatonin against hematological cancers, especially lymphoma. [ABSTRACT FROM AUTHOR]

To understand the origin of disease comorbidity and to identify the essential proteins and pathways underlying comorbid diseases, we developed LeMeDISCO (Large-Scale Molecular Interpretation of Disease Comorbidity), an algorithm that predicts disease comorbidities from shared mode of action proteins predicted by the artificial intelligence-based MEDICASCY algorithm. LeMeDISCO was applied to predict the occurrence of comorbid diseases for 3608 distinct diseases. Benchmarking shows that LeMeDISCO has much better comorbidity recall than the two molecular methods XD-score (44.5% vs. 6.4%) and the SAB score (68.6% vs. 8.0%). Its performance is somewhat comparable to the phenotype method-based Symptom Similarity Score, 63.7% vs. 100%, but LeMeDISCO works for far more cases and its large comorbidity recall is attributed to shared proteins that can help provide an understanding of the molecular mechanism(s) underlying disease comorbidity. The LeMeDISCO web server is available for academic users at: http://sites.gatech.edu/cssb/LeMeDISCO. LeMeDISCO predicts disease comorbidities and the proteins and pathways responsible for comorbidity, validated in ovarian cancer and coronary heart disease. [ABSTRACT FROM AUTHOR]

Sinonasal neuroendocrine neoplasms (SN-NENs) are rare and mostly include neuroendocrine carcinoma (NEC), whereas neuroendocrine tumor (NET) is exceptional in this site. Olfactory neuroblastoma (ONB) is a malignant neuroectodermal neoplasm arising in the nasal cavity. Albeit crucial for correct patients' management, the distinction of high grade ONB from NEC is challenging and requires additional diagnostic markers. The transcription factor SATB2 has been recently introduced in routine diagnostics as an immunohistochemical marker of distal intestine differentiation. No specific data are available about SATB2 and GATA3 expression in SN-NENs. GATA3, SATB2, and, for comparison, CDX2 expression were investigated in a series of epithelial and non-epithelial SN-NENs. We collected 26 cases of ONB and 7 cases of epithelial SN-NENs diagnosed and treated in our Institution. ONBs were graded according to Hyams' system and epithelial NENs were reclassified into 5 NECs, 1 MiNEN, and 1 amphicrine carcinoma. Immunohistochemistry was performed using standard automated protocols. Hyams' grades 1–3 ONBs stained diffusely and intensely for SATB2, whereas grade 4 ONBs and NECs were globally negative. The non-neuroendocrine component of MiNEN and the amphicrine carcinoma were strongly positive. GATA3 was heterogeneously and unpredictably expressed in Hyams' grades 1–3 ONBs, whereas grade 4 ONBs and NECs were completely negative. CDX2 was negative in all cases. Our study identifies, for the first time, SATB2 and GATA3 expression as features of Hyams' grades 1–3 ONBs, expands the spectrum of SATB2 and GATA3-positive neoplasms, and suggests that Hyams' grade 4 ONBs are not only clinically but also biologically different from low graded ONBs. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to explore the role of pantoprazole (PPZ) in affecting the sensitivity of cervical cancer (CC) cells to cisplatin.Methods: HeLa and CaSki cells were exposed to cisplatin and/or PPZ treatment. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, colony formation, flow cytometry, wound healing, and transwell assays were performed to detect cell viability, proliferation, apoptosis, migration, and invasion of CC cells, respectively. Then, expressions of Beclin-1, LC3, and p62 were measured by western blot. Rapamycin (Rapa), acting as an autophagy activator, was applied to confirm the effect of autophagy on the sensitivity of CC cells to cisplatin.Results: Cisplatin treatment suppressed cell viability and proliferation and accelerated apoptosis of CC cells. Combination of cisplatin and PPZ or PPZ alone significantly inhibited cell viability, proliferation, migration, and invasion, and increased cell apoptosis of CC cells. Cisplatin enhanced expression levels of Beclin1 and LC3II/I, and reduced p62 expression. Combination of cisplatin and PPZ significantly decreased the expression levels of Beclin1 and LC3II/I, but increased p62 expression. The autophagy activator, Rapa, eliminated the inhibitory effects of the combination of cisplatin and PPZ on autophagy, and enhanced cell viability, but inhibited apoptosis of CC cells.Conclusion: PPZ promotes the sensitivity of CC cells to cisplatin by inhibiting cisplatin-induced cell autophagy. [ABSTRACT FROM AUTHOR]

Background Little is known about the association between physical activity before cancer diagnosis and survival among lung cancer patients. In this pooled analysis of 11 prospective cohorts, we investigated associations of prediagnosis leisure-time physical activity (LTPA) with all-cause and lung cancer–specific mortality among incident lung cancer patients. Methods Using self-reported data on regular engagement in exercise and sports activities collected at study enrollment, we assessed metabolic equivalent hours (MET-h) of prediagnosis LTPA per week. According to the Physical Activity Guidelines for Americans, prediagnosis LTPA was classified into inactivity, less than 8.3 and at least 8.3 MET-h per week (the minimum recommended range). Cox regression was used to estimate hazard ratios (HRs) and 95% confidence interval (CIs) for all-cause and lung cancer–specific mortality after adjustment for major prognostic factors and lifetime smoking history. Results Of 20 494 incident lung cancer patients, 16 864 died, including 13 596 deaths from lung cancer (overall 5-year relative survival rate = 20.9%, 95% CI = 20.3% to 21.5%). Compared with inactivity, prediagnosis LTPA of more than 8.3 MET-h per week was associated with a lower hazard of all-cause mortality (multivariable-adjusted HR = 0.93, 95% CI = 0.88 to 0.99), but not with lung cancer–specific mortality (multivariable-adjusted HR = 0.99, 95% CI = 0.95 to 1.04), among the overall population. Additive interaction was found by tumor stage (P interaction =.008 for all-cause mortality and.003 for lung cancer–specific mortality). When restricted to localized cancer, prediagnosis LTPA of at least 8.3 MET-h per week linked to 20% lower mortality: multivariable-adjusted HRs were 0.80 (95% CI = 0.67 to 0.97) for all-cause mortality and 0.80 (95% CI = 0.65 to 0.99) for lung cancer–specific mortality. Conclusions Regular participation in LTPA that met or exceeded the minimum Physical Activity Guidelines was associated with reduced hazards of mortality among lung cancer patients, especially those with early stage cancer. [ABSTRACT FROM AUTHOR]

The human population's health, economy, and way of life have been seriously threatened by the Coronavirus Disease (COVID-19) pandemic. Patients with cancer are one of the special patient groups who faced additional difficulties during COVID-19, with additional problems in their basket. To minimise the sufferings, regular physical activity of any intensity lowers the chance of cancer progression while enhancing survival rates and Quality of Life (QoL). The lengthy indoor stay during the COVID-19 lockdown prompted inactivity among cancer patients, reducing their overall QoL. The purpose of this article is to ascertain how COVID-19-related physical inactivity affected cancer patients and their QoL. [ABSTRACT FROM AUTHOR]

Ovarian cancer (OC) is one of the deadliest gynecological cancers worldwide. Previous observational epidemiological studies have revealed associations between modifiable environmental risk factors and OC risk. However, these studies are prone to confounding, measurement error, and reverse causation, undermining robust causal inference. Mendelian randomization (MR) analysis has been established as a reliable method to investigate the causal relationship between risk factors and diseases using genetic variants to proxy modifiable exposures. Over recent years, MR analysis in OC research has received extensive attention, providing valuable insights into the etiology of OC as well as holding promise for identifying potential therapeutic interventions. This review provides a comprehensive overview of the key principles and assumptions of MR analysis. Published MR studies focusing on the causality between different risk factors and OC risk are summarized, along with comprehensive analysis of the method and its future applications. The results of MR studies on OC showed that higher BMI and height, earlier age at menarche, endometriosis, schizophrenia, and higher circulating β-carotene and circulating zinc levels are associated with an increased risk of OC. In contrast, polycystic ovary syndrome; vitiligo; higher circulating vitamin D, magnesium, and testosterone levels; and HMG-CoA reductase inhibition are associated with a reduced risk of OC. MR analysis presents a2 valuable approach to understanding the causality between different risk factors and OC after full consideration of its inherent assumptions and limitations. [ABSTRACT FROM AUTHOR]

Objective: To examine the association between (GWG) and epithelial ovarian cancer (EOC).Methods: We compared GWG between 670 incident EOC cases and 1,551 community controls from a population-based, case-control study conducted in Pennsylvania, Ohio, and New York from 2003 to 2008. Multivariable unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) associated with GWG adjusting for potential confounders. To explore the potential effect of maternal long-term weight retention after childbearing, we restricted analyses to women who began their childbearing years as normal/underweight and examined differences in EOC risk between those who were normal/underweight versus those who were overweight/obese at study baseline reference date.Results: Average GWG per full-term pregnancy did not differ between cases and controls. Among women who were normal/underweight at study baseline, greater average GWG was not associated with EOC (OR = 0.9, 0.8, 0.7 for quartiles 2, 3 and 4 of GWG gain, respectively, compared to quartile 1). In contrast, among women who were overweight/obese at study baseline, greater average GWG was positively associated with EOC (OR = 1.4, 1.8, 1.2, for quartiles 2, 3, and 4 compared to quartile 1; interaction p = 0.04).Conclusion: We posit that maternal post-partum weight retention and not gestational weight gain itself among normal/underweight women may impact subsequent risk of EOC. If our hypothesis is supported in other studies designed to assess this question directly, then counseling women on the importance of healthy weight management after a pregnancy could provide another means to help women reduce their risk of this often-fatal malignancy. [ABSTRACT FROM AUTHOR]

Physical activity is associated with decreased risk for many cancers. Studies on the association between physical activity and risk of bladder cancer are limited, and findings are inconsistent. Postmenopausal women (mean age = 63.3) were recruited into the Women's Health Initiative from 1993 to 1998. Self‐reported baseline information on physical activity and other covariates were available in 141 288 participants. Incident bladder cancer cases were collected through 2018 and centrally adjudicated. Hazard ratios (HRs) and 95% confidence intervals (CIs) were determined by Cox proportional hazard regression models. Effect modification due to smoking was assessed. During an average of 18.5 years of follow‐up, 817 bladder cancer cases were identified. Compared to physically inactive women, those who engaged in ≥15 MET‐hours/week of total physical activity, ≥8.75 MET‐hours/week of walking or ≥11.25 MET‐hours/week of moderate to vigorous physical activity had lower risk of bladder cancer (HR = 0.74, 95% CI: 0.59‐0.94, P for linear trend =.02; HR = 0.79, 95% CI: 0.63‐0.98, P for linear trend =.03; and HR = 0.76, 95% CI: 0.61‐0.94, P for linear trend =.02, respectively). No effect modification was found by smoking status (P for interaction =.06, 0.91 and 0.27, respectively). We found that total physical activity, walking and moderate to vigorous physical activity were inversely associated with bladder cancer incidence among postmenopausal women in a dose‐response manner. Physical activity may play a potential role in the primary prevention of bladder cancer. Further studies with objective measurements of physical activity are needed to confirm these findings. What's new? Women are diagnosed with bladder cancer at lower rates than men, but often have worse outcomes than men, even at similar stages. Studies of bladder cancer risk factors have more often focused on men than on women. Here, the authors examined different levels of physical activity as related to bladder cancer risk in postmenopausal women. Women who engaged in physical activity, whether it was walking or moderate‐to‐vigorous physical activity, had lower risk of bladder cancer than women who described themselves as physically inactive. [ABSTRACT FROM AUTHOR]

Purpose: Thyroid hormone receptors (THR) have manifold functions and are involved in the carcinogenesis of several tumor types. Within this study, we aimed to investigate the expression pattern (nuclear versus cytoplasmic) of the THR alpha and its impact on patients survival in ovarian cancer (OvCa). Methods: The presence of the thyroid hormone receptors THRα, THRα1 and − 2 was investigated in 156 ovarian cancer samples using immunohistochemistry (IHC) using semi-quantitative immunoreactivity (IR) scores and correlated with clinical, pathological data, subtype of ovarian cancer, clinical data, staining of 20 already described OvCa marker proteins and overall survival (OS). Results: Among all subtypes of OvCa, clear cell carcinomas showed the highest THRα expression. Furthermore, nuclear THRα was associated with a reduced survival in this subtype. However, nuclear expressed THRα1 turned out to be a positive prognosticator for all subtypes of OvCa patients. Nuclear THRα2 is a positive prognosticator for OvCa patients of the serous subtype. In contrast, cytoplasmic expression THRα2 was associated with a reduced OS in all subtypes of OvCa patients; while, cytoplasmic expression of THRα1 is associated with reduced OS in mucinous OvCa patients only. In addition, THRα expression correlates with gonadotropin receptors, steroid hormone receptors, TA-MUC1 and glycodelin. Conclusion: Depending on nuclear or cytoplasmic expression, our study shows that THRα and its isoforms 1 and 2 provide different prognostic information for ovarian cancer patients. Further investigations should analyze if THRs may represent new endocrine targets for the treatment of ovarian cancer. [ABSTRACT FROM AUTHOR]

Introduction: Relationship between renal cell carcinoma and physical activity is not clear. Objectives: This study aimed to review the relationship between renal cell carcinoma and physical activity. Methods: We searched valid databases such as PubMed/Medline, Web of Science and Scopus for search of English papers by 30/12/2018. Eleven articles were selected for final assessment. We used Kidney cancer, Exercise, Kidney Neoplasm, Renal cancer, Physical activity, Renal cell carcinoma, Physical inactivity and Sedentary Lifestyle or a combination of them in the title/abstracts as the keywords. Results: There were 37,742 subjects reviewed in this systematic review of eleven published papers including five standard case-control, three cohorts and three population-based case-control design. Conclusion: According to the results, physical activity has a reverse relationship with renal cell carcinoma. [ABSTRACT FROM AUTHOR]

Women of African ancestry have lower incidence of epithelial ovarian cancer (EOC) yet worse survival compared to women of European ancestry. We conducted a genome‐wide association study in African ancestry women with 755 EOC cases, including 537 high‐grade serous ovarian carcinomas (HGSOC) and 1,235 controls. We identified four novel loci with suggestive evidence of association with EOC (p < 1 × 10−6), including rs4525119 (intronic to AKR1C3), rs7643459 (intronic to LOC101927394), rs4286604 (12 kb 3′ of UGT2A2) and rs142091544 (5 kb 5′ of WWC1). For HGSOC, we identified six loci with suggestive evidence of association including rs37792 (132 kb 5′ of follistatin [FST]), rs57403204 (81 kb 3′ of MAGEC1), rs79079890 (LOC105376360 intronic), rs66459581 (5 kb 5′ of PRPSAP1), rs116046250 (GABRG3 intronic) and rs192876988 (32 kb 3′ of GK2). Among the identified variants, two are near genes known to regulate hormones and diseases of the ovary (AKR1C3 and FST), and two are linked to cancer (AKR1C3 and MAGEC1). In follow‐up studies of the 10 identified variants, the GK2 region SNP, rs192876988, showed an inverse association with EOC in European ancestry women (p = 0.002), increased risk of ER positive breast cancer in African ancestry women (p = 0.027) and decreased expression of GK2 in HGSOC tissue from African ancestry women (p = 0.004). A European ancestry‐derived polygenic risk score showed positive associations with EOC and HGSOC in women of African ancestry suggesting shared genetic architecture. Our investigation presents evidence of variants for EOC shared among European and African ancestry women and identifies novel EOC risk loci in women of African ancestry. What's new? Women of African ancestry have lower incidence of epithelial ovarian cancer (EOC) yet worse survival compared to women of European ancestry. To date, genome‐wide association studies (GWAS) have identified 30 common, low‐penetrant EOC susceptibility alleles. However, most studies were restricted to European ancestry women, and it remains to be determined whether there is any concordance among women of African descent. In this first GWAS conducted in women of African ancestry, the authors report ten novel associated SNPs. The results also suggest there may be some shared genetic architecture between women of European and African ancestry for susceptibility to ovarian cancer. [ABSTRACT FROM AUTHOR]

Background: The aim of the study was to evaluate trends of mortality and the number of years of life lost due to lung cancer in Poland, in the period 2000-2016.Methods: The study material was 375,151 death certificates of all inhabitants of Poland who died in the period 2000-2016 due to lung cancer. In order to calculate the number of years of life lost, the authors used indices: SEYLLp (Standard Expected Years of Life Lost per living person), SEYLLd (per deaths), APC (Annual Percentage Change) and AAPC (Average Annual Percentage Change).Results: The standardized death rate (SDR) due to lung cancer decreased in the analyzed period from 74.5 to 68.3 per 100,000 population (AAPC = -0.6%). The most rapid decrease was noted in the years 2008-2011 (APC = -2.2%). With regards to males, SDR decreased from 148.8 to 114.5 (AAPC = -1.7%), whereas in females, it increased from 25.7 to 37.6 (AAPC = 2.3%). The SEYLLp index, calculated per 100,000 inhabitants, increased from 1189.9 in the year 2000 to 1250.5 in the year 2016. The trend and pace of changes fluctuated. In 2000-2008, the SEYLLp index was increasing at a pace of 0.7%. This growth was followed by a decrease at a pace of -1.2%, noted in 2008-2011. After the year 2011, the indices started to grow at an annual pace of 0.4%. AAPC in the whole study period was 0.3%. Increased mortality in females was responsible for the increase in the number of lost years of life. SEYLLp values in this sex group increased from 464.8 in the year 2000 to 774.7 in the year 2016 (APC = 3.3%).With regards to males, SEYLLp values, calculated for 100,000 male population, decreased in the analyzed period from 1961.1 to 1758.3.Conclusions: Lung cancer still poses a serious epidemiological problem in Poland and the number of years of life lost due to this cause reflects social and economic implications of premature lung cancer-related mortality. There is a great need to educate, particularly women, and show effective ways of quitting smoking. [ABSTRACT FROM AUTHOR]

In this study, we aimed to evaluate site-specific cancer risks a ssociated with hyperthyroidism or hypothyroidism. We performed a systematic review of observational studies reporting associations between hyperthyroidism or hypothyroidism and subsequent site-specific cancer incidence, in MEDLINE and the COCHRANE library (inception-28/01/2019) (PROSPERO: CRD42019125094). We excluded studies with thyroid dysfunction evaluated as a cancer biomarker or after prior cancer diagnosis and those considering transient thyroid dysfunction during pregnancy or severe illnesses. Risk of bias was assessed using a modified Newcastle-Ottawa scale. Risk estimates were pooled using random-effects models when =5 studies reported data for a specific cancer site. Twenty studies were included, of which 15 contributed to the me ta-analysis. Compared to euthyroidism, hyperthyroidism was associated with higher risks of thyroid (pooled risk ratio: 4.49, 95%CI: 2.84-7.12), breast (pooled risk ratio: 1.20, 95%CI: 1.04-1.38), and prostate (pooled risk ratio: 1.35, 95%CI: 1.05-1.74), but not respiratory tract (pooled risk ratio: 1.06, 95%CI: 0.80-1.42) cancers. Hypothyroidism was associated with a higher risk of thyroid cancer within the first 10 years of follow-up on ly (pooled risk ratio: 3.31, 95%CI: 1.20-9.13). There was no or limited evidence of thyroid dysfunction-related risks of other cancer sites. In conclusion, thyroid dysfunction was associated with increased risks of thyroid, breast, and prostate cancers. However, it remains unclear whether these findings represent causal relationships because information on treatments and potential confounders was frequently lacking. [ABSTRACT FROM AUTHOR]

Immunosuppressive myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs) are associated with immunologic tolerance and poor prognosis in ovarian cancer (OvCa). We hypothesized that women with germline BRCA1 and BRCA2 mutation-associated (gBRCAm) OvCa would have fewer circulating immunosuppressive immune cells compared to those with BRCA wild-type (BRCAwt) disease during their early disease course (<5 years post-diagnosis) where gBRCAm is a favorable prognostic factor. We collected and viably froze peripheral blood mononuclear cells (PBMCs) from patients with recurrent OvCa olaparib clinical trials (NCT01445418/NCT01237067). Immune subset analyses were performed using flow cytometry for Tregs, exhausted CD8+ T cells, monocytes and MDSCs. Functional marker expression, including cytotoxic T lymphocyte-associated protein 4 (CTLA-4), T cell immunoglobulin and mucin domain 3 (TIM-3) and programmed cell death protein 1 (PD-1) was evaluated. Data were analyzed using FlowJo. Pretreatment PBMCs were collected from 41 patients (16 gBRCAm/25 BRCAwt). The percentage of MDSCs among viable CD45+ PBMC was lower in gBRCAm OvCa compared with BRCAwt OvCa (median 0.565 vs. 0.93%, P=0.0086) but this difference was not seen in those women >5 years post-diagnosis. CD8+ T cells among viable CD45+ PBMCs and CTLA-4+/CD8+ T cells were higher in gBRCAm carriers than patients with BRCAwt, in particular for those <5 years post-diagnosis (median 20.4 vs. 9.78%, P=0.031 and median MFI 0.19 vs. 0.22, P=0.0074, respectively). TIM-3 expression on Tregs was associated with poor progression-free survival, independent of gBRCAm status (P<0.001). Our pilot data suggested that patients with gBRCAm OvCa may have fewer circulating MDSCs but higher CD8+ T cells in PBMCs during their early disease course. This may contribute to the observed survival benefit for these women in their first post-diagnosis decade. [ABSTRACT FROM AUTHOR]

Breast cancer is the second leading cause of cancer-associated mortality among women worldwide, and the prevalence and mortality rates associated with this disease are high in Western countries. The melanoma-associated antigen (MAGE) family proteins are well-known tumor-specific antigens; this family includes >60 proteins that serve an important part in cell cycle withdrawal, neuronal differentiation and apoptosis. The aim of the present study was to identify a biomarker within the MAGE family that is specific for breast cancer. In the present study, the prognostic role of MAGE mRNA expression was investigated in patients with breast cancer using the Kaplan-Meier plotter database. The prognostic value of MAGE members in the different intrinsic subtypes of breast cancer was further investigated, as well as the clinicopathological features of the disease. The results of the present study indicated that patients with breast cancer that had high mRNA expression levels of MAGEA5, MAGEA8, MAGEB4 and MAGEB6 had an improved relapse-free survival, whereas those with high mRNA expression levels of MAGEB18 and MAGED4 did not. These results suggested that MAGEA5, MAGEA8, MAGEB4 and MAGEB6 may have roles as tumor suppressors in the occurrence and development of breast cancer, whereas MAGEB18 and MAGED4 may possess carcinogenic potential. MAGED2, MAGED3 and MAGEF1 had different effects depending on the type of breast cancer. In particular, high MAGEC3 mRNA expression was associated with worse RFS in lymph node-positive breast cancer, but with improved RFS in lymph node-negative breast cancer. In patients with wild-type TP53 and patients with different pathological grades of breast cancer, MAGEE2, MAGEH1 and MAGEL2 were more worthy of attention as potential prognostic factors. The results of the present study may help to elucidate the role of MAGE family members in the development of breast cancer, and may promote further research that identifies MAGE-targeting reagents for the treatment of breast cancer. [ABSTRACT FROM AUTHOR]

Recently, there have been encouraging findings suggesting that myeloid-derived suppressor cells (MDSCs) may be a good target for studying immune suppression in ovarian cancer. MDSCs are an abundance of immature myeloid cells that have demonstrated the ability to decrease tumor-infiltrating immune cells, increase the accrual of tumor-associated macrophages and regulatory T cells, as well as secrete various pro-inflammatory mediators and growth stimulating cytokines. Most studies on this topic utilized murine models, but there are limited reports in human subjects which have important limitations. With the majority of ovarian cancer patients presenting with distant metastases and a corresponding 5-year relative survival rate of < 30%, continued efforts are obligatory toward identifying potential prognostic factors. Given the difficulty of studying exposures in this patient population, as well as the existing immunologic characteristics of this cancer, there is growing interest in further identifying genetic and immunologic associations with patient survival. Furthermore, prognostic factors that may necessitate therapeutic intervention may significantly alter disease outlook. In this review paper, we address the current literature on MDSCs and their immunosuppressive behavior in ovarian cancer patients. While the previous studies on these cells in ovarian cancer have demonstrated some potential prognostic significance, there are many limitations to such studies including small sample sizes, inconsistent staging and histology, as well as inconsistent surface markers for the identification of MDSCs. Additionally, such studies include minimal patient characteristics involved with the clinical course of ovarian cancer. Here, we have proposed improving on studies analyzing MDSCs as a potential prognostic factor in ovarian cancer patients, as well as further identifying the potential of this novel prognostic factor in future care, through the use of a comprehensive epidemiologic model. [ABSTRACT FROM AUTHOR]