scholarly journals Y disruption, autosomal hypomethylation and poor male lung cancer survival

2020 ◽  
Author(s):  
Saffron A.G. Willis-Owen ◽  
Clara Domingo Sabugo ◽  
Elizabeth Starren ◽  
Liming Liang ◽  
Maxim B. Freidin ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Y Chromosome ◽  
Cancer Survival ◽  
Dna Hypomethylation ◽  
Specific Expression ◽  
Pulmonary Tissue ◽  
Risk Of Death ◽  
Increased Risk ◽  
Discovery Dataset ◽  
Male Specific

SummaryLung cancer is the most frequent cause of cancer death worldwide1. It is male predominant and for reasons that are unknown also associated with significantly worse outcomes in men2. Here we compared gene co-expression networks in affected and unaffected pulmonary tissue derived from 126 patients with Stage IA–IV lung cancer. We observed marked degradation of a sex-associated gene co-expression network in tumour tissue. The disturbance was linked to fractional loss of the Y chromosome and was detected in 28% of male tumours in the discovery dataset and 27% of male tumours in a 123 sample replication dataset. Depression of Y chromosome expression was accompanied by extensive autosomal DNA hypomethylation. The male specific H3K4 demethylase, KDM5D, was identified as an apex hub within this co-expression network. Male patients exhibiting relative tumour KDM5D deficiency had an increased risk of death in the discovery dataset (Hazard Ratio [HR] 3.80, 95% CI 1.40 – 10.3, P=0.009) and in an independent sample of 1,100 male lung tumours (HR 1.67, 95% CI 1.4-2.0, P=1.2⨯10−10). Our findings identify tumour-specific weakening of male-specific expression, in particular deficiency of KDM5D, as a common replicable prognostic marker and credible mechanism underlying sex disparity in cancer.

scholarly journals Y disruption, autosomal hypomethylation and poor male lung cancer survival

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Saffron A. G. Willis-Owen ◽  
Clara Domingo-Sabugo ◽  
Elizabeth Starren ◽  
Liming Liang ◽  
Maxim B. Freidin ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Survival ◽  
Prognostic Indicator ◽  
Sexually Dimorphic ◽  
Dna Hypomethylation ◽  
Curative Intent ◽  
Risk Of Death ◽  
Increased Risk ◽  
Stage Ia ◽  
Sex Disparity

AbstractLung cancer is the most frequent cause of cancer death worldwide. It affects more men than women, and men generally have worse survival outcomes. We compared gene co-expression networks in affected and unaffected lung tissue from 126 consecutive patients with Stage IA–IV lung cancer undergoing surgery with curative intent. We observed marked degradation of a sex-associated transcription network in tumour tissue. This disturbance, detected in 27.7% of male tumours in the discovery dataset and 27.3% of male tumours in a further 123-sample replication dataset, was coincident with partial losses of the Y chromosome and extensive autosomal DNA hypomethylation. Central to this network was the epigenetic modifier and regulator of sexually dimorphic gene expression, KDM5D. After accounting for prognostic and epidemiological covariates including stage and histology, male patients with tumour KDM5D deficiency showed a significantly increased risk of death (Hazard Ratio [HR] 3.80, 95% CI 1.40–10.3, P = 0.009). KDM5D deficiency was confirmed as a negative prognostic indicator in a further 1100 male lung tumours (HR 1.67, 95% CI 1.4–2.0, P = 1.2 × 10–10). Our findings identify tumour deficiency of KDM5D as a prognostic marker and credible mechanism underlying sex disparity in lung cancer.

scholarly journals Colorectal cancer survival among Ministry of National Guard-Health Affairs (MNG-HA) population 2009–2017: retrospective study

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Mesnad Alyabsi ◽  
Fouad Sabatin ◽  
Majed Ramadan ◽  
Abdul Rahman Jazieh
Keyword(s):  
Colorectal Cancer ◽  
Distant Metastasis ◽  
Cancer Survival ◽  
National Guard ◽  
Population Based ◽  
Risk Of Death ◽  
Cox Proportional Hazard ◽  
Kaplan Meier ◽  
Increased Risk ◽  
Cox Proportional Hazard Models

Abstract Background Colorectal cancer (CRC) is the most diagnosed cancer among males and third among females in Saudi Arabia, with up to two-third diagnosed at advanced stage. The objective of our study was to estimate CRC survival and determine prognostic factors. Methods Ministry of National Guard- Health Affairs (MNG-HA) registry data was utilized to identify patients diagnosed with CRC between 2009 and 2017. Cases were followed until December 30th, 2017 to assess their one-, three-, and five-year CRC-specific survivals. Kaplan-Meier method and Cox proportional hazard models were used to assess survival from CRC. Results A total of 1012 CRC patients were diagnosed during 2009–2017. Nearly, one-fourth of the patients presented with rectal tumor, 42.89% with left colon and 33.41% of the cases were diagnosed at distant metastasis stage. The overall one-, three-, and five-year survival were 83, 65 and 52.0%, respectively. The five-year survival was 79.85% for localized stage, 63.25% for regional stage and 20.31% for distant metastasis. Multivariate analyses showed that age, diagnosis period, stage, nationality, basis of diagnosis, morphology and location of tumor were associated with survival. Conclusions Findings reveal poor survival compared to Surveillance, Epidemiology, and End Results (SEER) population. Diagnoses at late stage and no surgical and/or perioperative chemotherapy were associated with increased risk of death. Population-based screening in this population should be considered.

scholarly journals Interstitial Lung Disease Associated with Lung Cancer: A Case–Control Study

2020 ◽  
Vol 9 (3) ◽  
pp. 700
Author(s):  
Quentin Gibiot ◽  
Isabelle Monnet ◽  
Pierre Levy ◽  
Anne-Laure Brun ◽  
Martine Antoine ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Case Control Study ◽  
Standard Of Care ◽  
Case Control ◽  
Risk Of Death ◽  
Increased Risk ◽  
Two Factors ◽  
Control Study

Interstitial lung disease (ILD) seems to be associated with an increased risk of lung cancer (LC) and to have a poorer prognosis than LC without ILD. The frequency of ILD in an LC cohort and its prognosis implication need to be better elucidated. This retrospective, observational, cohort study evaluated the frequency of ILD among LC patients (LC–ILD) diagnosed over a 2-year period. LC–ILD patients’ characteristics were compared to those with LC without ILD (LC–noILD). Lastly, we conducted a case–control study within this cohort, matching three LC–noILDs to each LC–ILD patient, to evaluate the ILD impact on LC patients’ prognoses. Among 906 LC patients, 49 (5.4%) also had ILD. Comparing LC–ILD to LC–noILD patients, respectively, more were men (85.7% vs. 66.2%; p = 0.02); adenocarcinomas were less frequent (47.1% vs. 58.7%, p = 0.08); median [range] and overall survival was shorter: (9 [range: 0.1–39.4] vs. 17.5 [range: 0.8–50.4] months; p = 0.01). Multivariate analysis (hazard ratio [95% confidence interval]) retained two factors independently associated with LC risk of death: ILD (1.79 [1.22–2.62]; p = 0.003) and standard-of-care management (0.49 [0.33–0.72]; p < 0.001). Approximately 5% of patients with a new LC diagnosis had associated ILD. ILD was a major prognosis factor for LC and should be taken into consideration for LC management. Further studies are needed to determine the best therapeutic strategy for the LC–ILD population.

scholarly journals CSF-1 and Ang-2 serum levels — prognostic and diagnostic partners in non-small cell lung cancer

ESMO Open ◽  
2018 ◽  
Vol 3 (5) ◽  
pp. e000349 ◽  
Author(s):  
Ana Luísa Coelho ◽  
Mónica Patrícia Gomes ◽  
Raquel Jorge Catarino ◽  
Christian Rolfo ◽  
Rui Manuel Medeiros ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Cancer Survival ◽  
Serum Levels ◽  
High Serum ◽  
Small Cell ◽  
Immune Checkpoints ◽  
Small Cell Lung ◽  
Increased Risk

BackgroundLung cancer is the most incident and lethal form of cancer, with late diagnosis as a major determinant of its bad prognosis. Immunotherapies targeting immune checkpoints improve survival, but positive results encompass only 30%–40% of the patients, possibly due to alternative pathways to immunosuppression, including tumour-associated macrophages (TAM). Colony stimulating factor-1 (CSF-1) is implicated in TAM differentiation and recruitment to tumours and in tumour angiogenesis, through a special setting of Tie-2-expressing macrophages, which respond to angiopoietin-2 (Ang-2). We evaluated the role of serum levels of CSF-1 in non-small cell lung cancer (NSCLC) prognosis and whether these could serve as biomarkers for NSCLC detection, along with Ang-2.Participants and methodsWe prospectively studied an unselected cohort of 145 patients with NSCLC and a group of 30 control individuals. Serum levels of Ang-2 and CSF-1 were measured by ELISA prior to treatment.ResultsSerum levels of CSF-1 and Ang-2 are positively correlated (p<0.000001). Individuals with high serum levels of CSF-1 have a 17-fold risk for NSCLC presence and patients with combined High Ang-2/CSF-1 serum levels present a 5-fold increased risk of having NSCLC. High Ang-2/CSF-1 phenotype is also associated with worst prognosis in NSCLC.ConclusionsCombined expression of CSF-1 and Ang-2 seems to contribute to worst prognosis in NSCLC and it is worthy to understand the basis of this unexplored partnership. Moreover, we think CSF-1 could be included as a biomarker in NSCLC screening protocols that can improve the positive predictive value of the current screening modalities, increase overall cost effectiveness and potentially improve lung cancer survival.

Deletion of GSTM1 and GSTT1 Genes and Lung Cancer Survival: a Systematic Review

2017 ◽  
Vol 103 (4) ◽  
pp. 338-344 ◽  
Author(s):  
Cristina Ramos Hernández ◽  
Cecilia Mouronte-Roibás ◽  
Juan Miguel Barros-Dios ◽  
Alberto Fernández-Villar ◽  
Alberto Ruano-Ravina
Keyword(s):  
Lung Cancer ◽  
Systematic Review ◽  
Cancer Survival ◽  
Lung Carcinogenesis ◽  
Biotransformation Enzymes ◽  
Increased Risk ◽  
Wide Range ◽  
Exogenous Agents ◽  
Glutathione S Transferases ◽  
Lung Cancer Survival

Purpose The mechanisms of lung carcinogenesis are not fully understood. Not all smokers develop lung cancer, indicating that genetic variations and other environmental factors may play an important role in its development. The human glutathione S-transferases (GSTs) have been associated with an increased risk of lung cancer. Glutathione S-transferases are phase II biotransformation enzymes that play a role in detoxifying a wide range of exogenous agents including carcinogens but also anticarcinogenic drugs. Methods We assessed the effect of allelic deletions in the GSTM1 and GSTT1 genotypes on lung cancer overall survival through a systematic review of the scientific literature after applying predefined inclusion and exclusion criteria. Results Most of the included studies found no effect or a tendency to worse survival for individuals with deletion of GSTs. Conclusions Further studies are necessary to understand the magnitude of the effect of the deletion of both genes on lung cancer survival.

Lung cancer in African-Americans and analysis of estrogen plus progestin use.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e18258-e18258
Author(s):  
Idoroenyi Usua Amanam ◽  
Rowan T. Chlebowski ◽  
Rebecca A. Nelson ◽  
Ravi Salgia
Keyword(s):  
Lung Cancer ◽  
Cox Regression ◽  
Controlled Trial ◽  
African Ancestry ◽  
Snp Array ◽  
Smoking History ◽  
Risk Of Death ◽  
Increased Risk ◽  
Estrogen Plus Progestin ◽  
The Impact

e18258 Background: The 15-year Women’s Health Initiative (WHI) sponsored by the NIH has provided a robust dataset on health risks for post-menopausal black women (BW), including the impact of hormone therapy (HRT) on cancer risk. Women enrolled in the WHI randomized, placebo-controlled trial and taking HRT demonstrated no increase in lung cancer incidence, but a statistically significant increase in mortality. However, effects of estrogen plus progestin on non-small cell lung cancer (NSCLC) incidence and outcomes has not been extensively examined, especially in African Ancestry (AA) and smoking history. Methods: Study participants were identified who met WHI clinical trial entry criteria. Cox regression models and Kaplan-Meier method plots were utilized. Analyses adjusted for age, BMI, education, smoking status, alcohol use, health status, and physical activity. A secondary analysis was performed on BW based on AA via Affymetrix Human SNP Array. Results: 161, 808 pts were enrolled from October 1993 to December 1998 (after exclusions total analytic cohort = 142,503). 128,682 (90%) were white (WW) and 13,821 (10%) were BW. BW had lower incidence of NSCLC compared to WW (HR 0.68; P < .0001). HRT participants had a 55% increase in incidence of NSCLC (p < .0001). Former alcohol users had highest risk of NSCLC incidence (HR 2.72; p < 0.0001). Age groups (55-59 years; 60-69 years; 70-79 years) were significantly less associated with BW compared to the youngest(50-54 years; P < .0001). HRT participants were more likely BW (OR 1.17; p < .0001). More current smokers were BW compared to WW (OR 1.75; p < .0001). HRT participants had increased risk of death to NSCLC (HR 1.29; p < .001). There was a trend for survival (p = 0.3667) in WW participants compared to BW (32 vs 28.0 months, respectively). BW who had > 80% AA had a decreased incidence NSCLC trend compared to BW with < 80% AA (HR 0.81; p = 0.2806). Conclusions: BW, especially those with high levels of AA had decreased incidence of NSCLC. Those patients who received HRT had higher incidence and death from NSCLC. Further investigations are required to understand the mechanisms that AA and HRT alter risks associated with NSCLC.

scholarly journals Antiangiogenic therapies in non-small-cell lung cancer

2018 ◽  
Vol 25 ◽  
pp. 45 ◽  
Author(s):  
A. Alshangiti ◽  
G. Chandhoke ◽  
P.M. Ellis
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Antiangiogenic Therapy ◽  
Small Cell ◽  
Small Cell Lung ◽  
Modest Improvement ◽  
Risk Of Death ◽  
Antiangiogenic Therapies ◽  
Increased Risk

Angiogenesis is frequent in non-small-cell lung cancer (nsclc) and is associated with more aggressive disease. Many clinical trials have evaluated the addition of antiangiogenic therapy to standard therapies for patients with nsclc. Bevacizumab, a monoclonal antibody directed against serum vascular endothelial growth factor, in combination with carboplatin–paclitaxel chemotherapy, has been shown to improve survival for patients with nsclc. However, bevacizumab-based therapy is not suitable for many nsclc patients, including those with squamous histology, poor performance status, brain metastases, and the presence of bleeding or thrombotic disorders. Similar efficacy has also been seen with carboplatin–pemetrexed followed by maintenance pemetrexed chemotherapy. In the second-line setting, the addition of ramucirumab to docetaxel—or the addition of bevacizumab to paclitaxel—has resulted in a modest improvement in efficacy, although the clinical importance of those findings is questionable. Many trials in nsclc have also evaluated oral antiangiogenic compounds, both in the first line in combination with chemotherapy and upon disease progression either as combination or single-agent therapy. No clear improvements in overall survival have been observed, although a subgroup analysis of a trial evaluating the addition of nintedanib to docetaxel showed improved survival that was limited to patients with adenocarcinoma. Those findings require validation, however. All of the oral antiangiogenic agents result in added toxicities. Some agents have resulted in an increased risk of death, limiting their development. Available evidence supports a limited number of antiangiogenic therapies for patients with nsclc, but no biomarkers to help in patient selection are currently available, and additional translational research is needed to identify predictive biomarkers for antiangiogenic therapy.

scholarly journals Severity of COVID-19 in patients with lung cancer: evidence and challenges

2021 ◽  
Vol 9 (3) ◽  
pp. e002266
Author(s):  
Antonio Passaro ◽  
Christine Bestvina ◽  
Maria Velez Velez ◽  
Marina Chiara Garassino ◽  
Edward Garon ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Care ◽  
Large Scale ◽  
Lung Cancer Screening ◽  
Healthcare Services ◽  
Smoking History ◽  
Risk Of Death ◽  
Increased Risk ◽  
Healthcare Crisis ◽  
The Impact

Cancer patients are highly vulnerable to SARS-CoV-2 infections due to frequent contacts with the healthcare system, immunocompromised state from cancer or its therapies, supportive medications such as steroids and most importantly their advanced age and comorbidities. Patients with lung cancer have consistently been reported to suffer from an increased risk of death compared with other cancers. This is possibly due to the combination of specific pathophysiological aspects, including underlying pulmonary compromise due to smoking history and the increased specific pressures on respiratory healthcare services caused by the related pandemic. Rationally and safely treating patients with lung cancer during the pandemic has become a continuous challenge over the last year. Deciding whether to offer, modify, postpone or even cancel treatments for this particular patient’s population has become the crucial recurrent dilemma for lung cancer professionals. Chemotherapy, immunotherapy and targeted agents represent distinct risks factors in the context of COVID-19 that should be balanced with the short-term and long-term consequences of delaying cancer care. Despite the rapid and persistent trend of the pandemic, declared by WHO on March 11, 2020, and still ongoing at the time of writing (January 2021), various efforts were made by oncologists worldwide to understand the impact of COVID-19 on patients with cancer. Adapted recommendations of our evidence-based practice guidelines have been developed for all stakeholders. Different small and large-scale registries, such as the COVID-19 and Cancer Consortium (CCC19) and Thoracic Cancers International COVID-19 Collaboration quickly collected data, supporting cancer care decisions under the challenging circumstance created by the COVID-19 pandemic. Several recommendations were developed as guidance for prioritizing the various aspects of lung cancer care in order to mitigate the adverse effects of the COVID-19 healthcare crisis, potentially reducing the morbidity and mortality of our patients from COVID-19 and from cancer. These recommendations helped inform decisions about treatment of established disease, continuation of clinical research and lung cancer screening. In this review, we summarize available evidence regarding the direct and indirect impact of the COVID-19 pandemic on lung cancer care and patients.

Effect of zoledronic acid (Z) treatment based on serum parathyroid hormone (PTH) levels in patients (pts) with malignant bone disease

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 8610-8610 ◽  
Author(s):  
A. Berruti ◽  
L. Dogliotti ◽  
M. Tampellini ◽  
A. Lipton ◽  
V. Hirsh ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Lung Cancer ◽  
Bone Metastases ◽  
Solid Tumors ◽  
Bone Lesion ◽  
Small Subset ◽  
Prognostic Information ◽  
Risk Of Death ◽  
Increased Risk ◽  
Serum Pth

8610 Background: Z prevents skeletal-related events (SREs) in pts with bone metastases or multiple myeloma. However, secondary hyperparathyroidism and increased PTH may stimulate osteoclast activity and tumor growth, thus potentially limiting the efficacy of Z. Methods: Serum PTH was assessed at baseline and every 3 months in 1,068 pts enrolled in 3 randomized trials: 547 received Z, and 521 received placebo or pamidronate. Results: 213 (20%) pts had elevated PTH at baseline, and 105 of 547 (19%) pts had elevated PTH during Z treatment. In patients with normal baseline PTH, Z significantly reduced the incidence of SREs and delayed time to first SRE compared with control, whereas the risk of SREs was not reduced in patients with elevated baseline PTH. In prostate cancer patients, Z significantly decreased the risk of death compared with placebo in pts with normal baseline PTH (relative risk [RR] = 0.72; 95% confidence interval [CI]: 0.55, 0.94; P = .015). No survival advantage was observed in this subpopulation among pts with lung cancer or other solid tumors. In the small subset of pts with elevated PTH during Z treatment, there was an increased risk of death (for breast cancer pts, RR = 1.68 [95% CI: 1.10, 2.56]; P = .016; for prostate cancer pts, RR = 2.92 [95% CI: 1.83, 4.67]; P < .001). Additionally, elevated PTH during Z treatment in prostate cancer pts also significantly correlated with an increased risk of bone lesion progression (RR = 1.54 [95% CI: 1.09, 2.17]; P = .015). Elevated PTH during treatment did not affect the incidence or time to onset of SREs. Among pts with lung cancer or other solid tumors, elevated PTH during Z treatment did not provide any predictive or prognostic information. Conclusions: PTH levels either at baseline or during Z treatment appear to correlate with disease progression and the clinical benefit of Z in pts with bone metastases from certain types of cancer. This retrospective analysis suggests the importance of PTH status in patients undergoing Z treatment. Normalization of PTH levels may increase the benefit of Z. [Table: see text]

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