Lung cancer is the leading cause of death from cancer worldwide and causes more deaths than breast, colorectal and cervical cancers combined. The five-year survival rate for lung cancer in the UK is ...approximately 15%. Over many years, lung cancer has failed to attract the attention and resources given to other cancers; it has also been stigmatised by a culture of blame, attributable to the sufferer because of smoking. Anyone can develop lung cancer, and between 15% and 20% of people with this diagnosis have never smoked. Many patients with lung cancer are diagnosed at late stages; therefore, early detection is pivotal to improving their survival. Dentists and their teams could potentially play a role in the public perception, prevention and detection of lung cancer.
At the time of cancer diagnosis, body mass index (BMI) is inversely correlated with lung cancer risk, which may reflect reverse causality and confounding due to smoking behavior. We used two‐sample ...univariable and multivariable Mendelian randomization (MR) to estimate causal relationships of BMI and smoking behaviors on lung cancer and histological subtypes based on an aggregated genome‐wide association studies (GWASs) analysis of lung cancer in 29 266 cases and 56 450 controls. We observed a positive causal effect for high BMI on occurrence of small‐cell lung cancer (odds ratio (OR) = 1.60, 95% confidence interval (CI) = 1.24‐2.06, P = 2.70 × 10−4). After adjustment of smoking behaviors using multivariable Mendelian randomization (MVMR), a direct causal effect on small cell lung cancer (ORMVMR = 1.28, 95% CI = 1.06‐1.55, PMVMR = .011), and an inverse effect on lung adenocarcinoma (ORMVMR = 0.86, 95% CI = 0.77‐0.96, PMVMR = .008) were observed. A weak increased risk of lung squamous cell carcinoma was observed for higher BMI in univariable Mendelian randomization (UVMR) analysis (ORUVMR = 1.19, 95% CI = 1.01‐1.40, PUVMR = .036), but this effect disappeared after adjustment of smoking (ORMVMR = 1.02, 95% CI = 0.90‐1.16, PMVMR = .746). These results highlight the histology‐specific impact of BMI on lung carcinogenesis and imply mediator role of smoking behaviors in the association between BMI and lung cancer.
What's new?
Lung cancer risk appears to be inversely correlated with BMI, which could be due to a variety of factors. Here, the authors used Mendelian randomization (MR) to look for a causal effect of BMI on lung cancer. MR uses genetic variants as instrumental variables, and avoids the effects of confounding factors. However, linkage disequilibrium with causal variants may interfere with the results. After adjustment for smoking, the authors found a direct causal effect of BMI on small cell lung cancer, and an inverse effect on lung adenocarcinoma. These results highlight that the effect of BMI varies significantly depending on histology.
Common genetic variants associated with lung cancer have been well studied in the past decade. However, only 12.3% heritability has been explained by these variants. In this study, we investigate the ...contribution of rare variants (RVs) (minor allele frequency <0.01) to lung cancer through two large whole exome sequencing case-control studies. We first performed gene-based association tests using a novel Bayes Factor statistic in the International Lung Cancer Consortium, the discovery study (European, 1042 cases vs. 881 controls). The top genes identified are further assessed in the UK Biobank (European, 630 cases vs. 172 864 controls), the replication study. After controlling for the false discovery rate, we found two genes, CTSL and APOE, significantly associated with lung cancer in both studies. Single variant tests in UK Biobank identified 4 RVs (3 missense variants) in CTSL and 2 RVs (1 missense variant) in APOE stongly associated with lung cancer (OR between 2.0 and 139.0). The role of these genetic variants in the regulation of CTSL or APOE expression remains unclear. If such a role is established, this could have important therapeutic implications for lung cancer patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The International Association for the Study of Lung Cancer (IASLC) Board of Directors convened a computed tomography (CT) Screening Task Force to develop an IASLC position statement, after the ...National Cancer Institute press statement from the National Lung Screening Trial showed that lung cancer deaths fell by 20%. The Task Force's Position Statement outlined a number of the major opportunities to further improve the CT screening in lung cancer approach, based on experience with cancer screening from other organ sites.
The IASLC CT Screening Workshop 2011 further developed these discussions, which are summarized in this report. The recommendation from the workshop, and supported by the IASLC Board of Directors, was to set up the Strategic CT Screening Advisory Committee (IASLC-SSAC). The Strategic CT Screening Advisory Committee is currently engaging professional societies and organizations who are stakeholders in lung cancer CT screening implementation across the globe, to focus on delivering guidelines and recommendations in six specific areas: (i) identification of high-risk individuals for lung cancer CT screening programs; (ii) develop radiological guidelines for use in developing national screening programs; (iii) develop guidelines for the clinical work-up of “indeterminate nodules” resulting from CT screening programmers; (iv) guidelines for pathology reporting of nodules from lung cancer CT screening programs; (v) recommendations for surgical and therapeutic interventions of suspicious nodules identified through lung cancer CT screening programs; and (vi) integration of smoking cessation practices into future national lung cancer CT screening programs.
Lung cancer remains the leading cause of cancer death worldwide, with 15% to 20% occurring in never smokers. To assess genetic determinants for prognosis among never smokers, we conducted a ...genome-wide investigation in the International Lung Cancer Consortium (ILCCO).
Genomic and clinical data from 1,569 never-smoking patients with lung cancer of European ancestry from 10 ILCCO studies were included. HRs and 95% confidence intervals of overall survival were estimated. We assessed whether the associations were mediated through mRNA expression-based 1,553 normal lung tissues from the lung expression quantitative trait loci (eQTL) dataset and Genotype-Tissue Expression (GTEx). For cross-ethnicity generalization, we assessed the associations in a Japanese study (
= 887).
One locus at 13q22.2 was associated with lung adenocarcinoma survival at genome-wide level, with carriers of rs12875562-T allele exhibiting poor prognosis HR = 1.71 (1.41-2.07),
= 3.60 × 10
, and altered mRNA expression of
in lung tissue (GTEx,
= 9.40 × 10
; Lung eQTL dataset,
= 0.003). Furthermore, 2 of 11 independent loci that reached the suggestive significance level (
< 10
) were significant eQTL affecting mRNA expression of nearby genes in lung tissues, including
at 1p36.13 and
at 9q34.3. One locus encoding
at 4p14 showed associations in both European HR = 0.50 (0.38-0.66),
= 6.92 × 10
and Japanese populations HR = 0.79 (0.67-0.94),
= 0.007.
Based on the largest genomic investigation on the lung cancer prognosis of never smokers to date, we observed that lung cancer prognosis is affected by inherited genetic variants.
We identified one locus near
at genome-wide level and several potential prognostic genes with
-effect on mRNA expression. Further functional genomics work is required to understand their role in tumor progression.
Head and neck cancer (HNC) is the eighth most common cancer in the UK, with over 12,000 new cases every year. The incidence of HNC is predicted to increase by 33% by 2035. Risk modelling produces ...personalised risk estimates for specific diseases, which can be used to inform education, screening programmes and recruitment to clinical trials. The present study describes the development and validation of the first risk prediction model for absolute risk of HNC, using a nested case-control study within the UK Biobank dataset. The UK Biobank recruited 502,647 individuals aged 40-69 years from around the UK. In total, 859 cases of HNC were identified, with 253 incident cases (individuals who developed HNC in the 7 years following recruitment to the UK Biobank study). Logistic regression was used to develop the model, then the model performance was validated using a cohort from the North West of England. Overall, increasing age, male sex, positive history of smoking and alcohol consumption and higher levels of material deprivation were significantly associated with a higher risk of HNC. Consuming at least five portions of fruit and vegetables per day, exercising at least once per week and higher BMI offered a protective effect against HNC. The C-statistic was 0.69 95% confidence interval (CI), 0.66-0.71 and the model displayed good calibration. Upon external validation, the C-statistic was 0.64 (95% CI, 0.60-0.68) with reasonable calibration. The model developed and validated in the present study allows calculation of a personalised risk estimate for HNC. This could be used to guide clinicians when counselling individuals on risk behaviour, and there is potential for such models to inform recruitment to screening trials.
Epigenetic biomarkers in lung cancer Liloglou, Triantafillos; Bediaga, Naiara G; Brown, Benjamin R.B ...
Cancer letters,
01/2014, Letnik:
342, Številka:
2
Journal Article
Recenzirano
Abstract Lung cancer mortality is strongly associated with the predominant diagnosis of late stage lesions that hampers effective therapy. Molecular biomarkers for early lung cancer detection is an ...unmet public health need and the lung cancer research community worldwide is putting a lot of effort to utilise major lung cancer population programmes in order to develop such molecular tools. The study of cancer epigenetics in the last decade has radically altered our views in cancer pathogenesis, providing new insights in biomarker development for risk assessment, early detection and therapeutic stratification. DNA methylation and miRNAs have rapidly emerged as potential biomarkers in body fluids showing promise to assist the clinical management of lung cancer. These new developments are exemplified in this review, demonstrating the huge potential of clinical cancer epigenetics, but also critically discussing the necessary validation steps to bring epigenetic biomarkers towards clinical implementation and the weaknesses of current biomarker studies.
•Minimising harms is critical in lung cancer screening implementation.•We report cumulative real-world lung cancer screening data from the UK.•Reported harms, including false positive and benign ...resection rates, are low.•Outcomes are comparable to, and in some aspects superior to, published RCTs.
Low-dose CT (LDCT) screening reduces lung cancer specific mortality. Several countries, including the UK, are evaluating the clinical impact and cost-effectiveness of LDCT screening using the latest evidence. In this paper we report baseline screening performance from five UK-based lung cancer screening programmes.
Data was collected at baseline from each screening programme. Measures of performance included prevalence of screen detected lung cancer, rate of surveillance imaging for indeterminate findings and surgical resection rates. Screening related harms were assessed by measuring false positive rates, number of invasive tests with associated complications in individuals without lung cancer and benign surgical resection rates.
A total of 11,148 individuals had a baseline LDCT scan during the period of analysis (2011 to 2020). Overall, 84.7% (n = 9,440) of baseline LDCT scans were categorised as negative, 11.1% (n = 1,239) as indeterminate and 4.2% (n = 469) as positive. The prevalence of screen detected lung cancer was 2.2%, ranging between 1.8% and 4.4% for individual programmes. The surgical resection rate was 66% (range 46% to 83%) and post-surgical 90-day mortality for those with lung cancer 1.2% (n = 2/165). The false positive rate was 2% (n = 219/10,898) and of those with a positive result, one in two had lung cancer diagnosed (53.3%). An invasive test was required in 0.6% (n = 61/10,898) of screening attendees without lung cancer; there were no associated major complications or deaths. The benign surgical resection rate was 4.6% (n = 8/173), equating to 0.07% of the screened population.
The performance of UK-based lung cancer screening programmes, delivered within or aligned to the National Health Service, compares favourably to published clinical trial data. Reported harms, including false positive and benign surgical resection rates are low. Ongoing monitoring of screening performance is vital to ensure standards are maintained and harms minimised.
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