Dataset Information

Y disruption, autosomal hypomethylation and poor male lung cancer survival.

ABSTRACT: Lung 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.

SUBMITTER: Willis-Owen SAG

PROVIDER: S-EPMC8203787 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Y disruption, autosomal hypomethylation and poor male lung cancer survival.

Willis-Owen Saffron A G SAG Domingo-Sabugo Clara C Starren Elizabeth E Liang Liming L Freidin Maxim B MB Arseneault Madeleine M Zhang Youming Y Lu Shir Kiong SK Popat Sanjay S Lim Eric E Nicholson Andrew G AG Riazalhosseini Yasser Y Lathrop Mark M Cookson William O C WOC Moffatt Miriam F MF

Scientific reports 20210614 1

Lung 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. ...[more]

PMID: 34127738

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Project description:IntroductionLung cancer is a leading cause of cancer incidence and death in the United States. Although most firefighters are fit and do not smoke, they are exposed to many known carcinogens during and in the aftermath of firefighting activities. Comprehensive epidemiologic investigations on lung cancer survival for both career and volunteer firefighters have not been undertaken.MethodsData from the Florida Cancer Data System (1981-2014) were linked with firefighter certification records from the Florida State Fire Marshal's Office to identify all patients of this occupational group; lung cancer cause-specific survival data were compared with other occupational groups using Cox regression models with occupation as the main effect. Adjusted hazard ratios (aHR) and 95% confidence intervals (95% CI) were calculated.ResultsOut of 210,541 male lung cancer cases diagnosed in Florida (1981-2014), 761 were firefighters (604 career, 157 volunteer). Lung cancer death was similar between volunteer (75.2%) and career firefighters (74.0%) but lower than non-firefighters (80.0%). Survival at 5 years was higher among firefighters (29.7%; career: 30.3%; volunteer: 27.4%) than non-firefighters (23.8%). In a multivariable model, compared with non-firefighters, firefighters have significantly higher cause-specific survival (aHR = 0.84; 95% CI: 0.77-0.91; p < 0.001). However, there were no significant survival differences between career and volunteer firefighters (1.14; 0.93-1.39; p = 0.213). In a separate multivariable model with firefighters as the comparator, other broad occupational groups had significantly lower cause-specific survival [white collar: 1.11 (1.02-1.21); blue collar: 1.15 (1.05-1.25); service: 1.13 (1.03-1.25); others/unknown: 1.21 (1.12-1.32); all p-values < 0.02].ConclusionLung cancer survival is significantly higher among firefighters compared with non-firefighters, but there is no significant difference between career and volunteer firefighters. Improved survival for firefighters might be due to a healthy worker effect, lower smoking prevalence relative to other worker groups, and possibly superior treatment adherence and compliance. Many firefighters are cross-trained as EMTs/paramedics and possess a level of medical knowledge that may favorably impact treatment engagement and better navigation of complex cancer care.

Dataset Information

Y disruption, autosomal hypomethylation and poor male lung cancer survival.

Publications

Y disruption, autosomal hypomethylation and poor male lung cancer survival.

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