scholarly journals Rare, pathogenic germline variants in Fanconi Anemia genes increase risk for squamous lung cancer

2018 ◽  
Author(s):  
Myvizhi Esai Selvan ◽  
Robert J. Klein ◽  
Zeynep H. Gümüş
Keyword(s):  
Lung Cancer ◽  
High Risk ◽  
Fanconi Anemia ◽  
Early Stage ◽  
Statistical Tests ◽  
Squamous Carcinoma ◽  
Joint Analysis ◽  
Germline Variants ◽  
Pathogenic Variants ◽  
Squamous Lung Cancer

AbstractPurposeLung cancer is the leading cause of cancer deaths worldwide, with substantially better prognosis in early stage as opposed to late stage disease. Identifying genetic factors for lung squamous carcinoma (SqCC) risk will enable their use in risk stratification, and personalized intensive surveillance, early detection, and prevention strategies for high-risk individuals.Study Design and ParticipantsWe analyzed whole-exome sequencing datasets of 318 cases and 814 controls (discovery cohort) and then validated our findings in an independent cohort of 444 patients and 3,479 controls (validation cohort), all of European descent, totaling a combined cohort of 765 cases and 4,344 controls. We focused on rare pathogenic variants found in the ClinVar database and used penalized logistic regression to identify genes in which such variants are enriched in cases. All statistical tests were two-sided.ResultsWe observed an overall enrichment of rare, deleterious germline variants in Fanconi Anemia genes in cases with SqCC (joint analysis OR=3.08, p=1.4e-09, 95% confidence interval [CI]=2.2–4.3). Consistent with previous studies, BRCA2 in particular exhibited an increased overall burden of rare, deleterious variants (joint OR=3.2, p=8.7e-08, 95% CI=2.1–4.7). More importantly, rare deleterious germline variants were enriched in Fanconi Anemia genes even without the BRCA2 rs11571833 variant that is strongly enriched in lung SqCC cases (joint OR=2.76, p=7.0e-04, 95% CI=1.6–4.7).ConclusionsThese findings can be used towards the development of a genetic diagnostic test in the clinic to identify SqCC high-risk individuals, who can benefit from personalized programs, improving prognosis.

scholarly journals Rare, Pathogenic Germline Variants in Fanconi Anemia Genes Increase Risk for Squamous Lung Cancer

2018 ◽  
Vol 25 (5) ◽  
pp. 1517-1525 ◽  
Author(s):  
Myvizhi Esai Selvan ◽  
Robert J. Klein ◽  
Zeynep H. Gümüş
Keyword(s):  
Lung Cancer ◽  
Fanconi Anemia ◽  
Germline Variants ◽  
Increase Risk ◽  
Squamous Lung Cancer

scholarly journals Multi-Institutional Prospective Validation of Prognostic mRNA Signatures in Early Stage Squamous Lung Cancer (Alliance)

2020 ◽  
Vol 15 (11) ◽  
pp. 1748-1757
Author(s):  
Raphael Bueno ◽  
William G. Richards ◽  
David H. Harpole ◽  
Karla V. Ballman ◽  
Ming-Sound Tsao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Early Stage ◽  
Squamous Lung Cancer

scholarly journals Outcomes After Surgery in High-Risk Patients With Early Stage Lung Cancer

2016 ◽  
Vol 101 (3) ◽  
pp. 1043-1051 ◽  
Author(s):  
Manu S. Sancheti ◽  
John N. Melvan ◽  
Rachel L. Medbery ◽  
Felix G. Fernandez ◽  
Theresa W. Gillespie ◽  
...  
Keyword(s):  
Lung Cancer ◽  
High Risk ◽  
Early Stage ◽  
Early Stage Lung Cancer ◽  
High Risk Patients ◽  
Risk Patients ◽  
Stage Lung Cancer

scholarly journals A serum circulating miRNA diagnostic test to identify asymptomatic high‐risk individuals with early stage lung cancer

2011 ◽  
Vol 3 (8) ◽  
pp. 495-503 ◽  
Author(s):  
Fabrizio Bianchi ◽  
Francesco Nicassio ◽  
Matteo Marzi ◽  
Elena Belloni ◽  
Valentina Dall'Olio ◽  
...  
Keyword(s):  
Lung Cancer ◽  
High Risk ◽  
Diagnostic Test ◽  
Early Stage ◽  
Early Stage Lung Cancer ◽  
Circulating Mirna ◽  
Stage Lung Cancer

scholarly journals Research in progress—LungSEARCH: a randomised controlled trial of surveillance for the early detection of lung cancer in a high-risk group

Thorax ◽  
2015 ◽  
Vol 71 (1) ◽  
pp. 91-93 ◽  
Author(s):  
Stephen G Spiro ◽  
Allan Hackshaw
Keyword(s):  
Lung Cancer ◽  
High Risk ◽  
Early Stage ◽  
Controlled Trial ◽  
Prospective Trial ◽  
High Risk Group ◽  
Early Stage Lung Cancer ◽  
Link Type ◽  
Screening Strategies ◽  
Randomised Controlled

Low-dose CT screening for lung cancer is effective but expensive. Therefore, cheaper or more focused screening strategies may be required. LungSEARCH is a randomised prospective trial of 1568 high-risk individuals (ie, current or former moderate to heavy smokers with mild/moderate COPD) who undergo either annual sputum cytology/cytometry testing or no screening. Those with abnormal sputum then receive annual CT and fluorescent bronchoscopy for the remainder of 5 years, to identify early stage lung cancer. It is hoped that these simple initial tests could identify those requiring expensive CT scans, and the aim is to demonstrate a stage shift towards early stage cancers.Trial registration numbers ISRCTN: ISRCTN80745975, clinicaltrials.gov: NCT00512746.

scholarly journals TERT Mutation was Associated with the Risk of Recurrence in Lung Adenocarcinoma with A Micropapillary Pattern

2020 ◽  
Author(s):  
Fenfang Wang ◽  
Lu Xu ◽  
Qing Hao ◽  
Chenghui Li ◽  
Qihuan Wu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
High Risk ◽  
Lung Adenocarcinoma ◽  
Early Stage ◽  
Growth Factor Receptor ◽  
Egfr Mutations ◽  
Molecular Characteristics ◽  
Risk Of Recurrence ◽  
Tert Mutation ◽  
Micropapillary Pattern

Abstract Background: Lung adenocarcinoma with a micropapillary pattern (MPPAC) is the histological subtype of lung cancer. It has attracted increasing attention, especially regarding its association with poor prognosis, including the predisposition towards recurrence and metastasis. Although MPPAC has been described in early-stage cases, only a few studies have reported the correlation between disease-specific prognosis and gene mutation of MPPAC. This study aimed to clarify the common genetic mutations and the prognostic characteristics in MPPAC patients.Methods: A total of 17 patients whose surgical pathology was defined as MPPAC were followed up, the molecular characteristics were elucidated by next-generation sequencing, and the prognostic characteristics were analyzed. Results: Epidermal growth factor receptor (EGFR) mutations were identified in 11/17 (65%) of patients. TP53 alterations were identified in 10/17 (59%). Other common mutations include ATM (18%), KRAS (18%), SDHA (18%), and TERT (18%). MPPAC patients harboring EGFR and TERT mutations were at a high risk of tumor recurrence, while TP53 might be associated with a low risk of recurrence. Conclusions: TERT mutation was more frequently harbored in MPPAC patients than in the other histological type of lung cancer, and such patients were at a high risk of recurrence. So TERT mutation might be associated with adverse prognosis in MPPAC patients.

scholarly journals Hereditary pancreatic cancer

2021 ◽  
Author(s):  
Kodai Abe ◽  
Minoru Kitago ◽  
Yuko Kitagawa ◽  
Akira Hirasawa
Keyword(s):  
Pancreatic Cancer ◽  
High Risk ◽  
Precision Medicine ◽  
Cancer Patients ◽  
Genome Wide Association Study ◽  
Parp Inhibitor ◽  
Cancer Syndrome ◽  
Germline Variants ◽  
Panel Testing ◽  
Pathogenic Variants

AbstractPancreatic cancer is associated with both family and hereditary cancer syndromes. Multigene panel testing for pancreatic cancer detected the germline variants BRCA1/2, PALB2, ATM, TP53, MLH1, STK11/LKB1, APC, CDKN2A, and SPINK1/PRSS1 as high-risk genes. A latest genome-wide association study revealed the common, but low-risk germline variants in pancreatic cancer patients. Active pancreatic surveillance using magnetic resonance imaging and endoscopic ultrasound is recommended for high-risk individuals who have a family history of pancreatic cancer or harbor these germline pathogenic variants to improve the detection rate and prognosis of pancreatic cancer. Since poly-ADP-ribose polymerase (PARP) inhibitor has been shown to be effective in improving the prognosis of BRCA-positive pancreatic cancer as well as hereditary breast and ovarian cancer syndrome, PARP inhibitor therapy is currently being applied as precision medicine to pancreatic cancer patients harboring the BRCA1/2 germline variant. This review highlights the importance of surveillance for germline pathogenic variants in pancreatic cancer and is expected to lead to improvements in the diagnosis and prevention of pancreatic cancer as well as facilitate the development of effective therapeutic strategies and precision medicine.

Camrelizumab in the treatment of patients with advanced lung cancer: A multicenter, prospective, cohort study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21650-e21650
Author(s):  
Rong Wang ◽  
Mei Ji ◽  
Meiqi Shi ◽  
Dong Hua ◽  
Lianke Liu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cohort Study ◽  
Prospective Cohort Study ◽  
Real World ◽  
Prospective Cohort ◽  
Early Stage ◽  
Antitumour Activity ◽  
Objective Response ◽  
Squamous Carcinoma ◽  
Advanced Lung Cancer

e21650 Background: Camrelizumab is a humanized PD-1 monoclonal antibody. The efficacy of camrelizumab monotherapy or combined with chemotherapy in the treatment of advanced NSCLC had been demonstrated with promising anti-tumor activity in previous studies. However, in the real-world clinical practice, the activity of camrelizumab in patients with advanced lung cancer is poorly characterised. We sought to analyse the antitumour activity and toxicity of camrelizumab in advanced lung cancer to explore benefit subgroups and optimal treatments. Methods: This is a multicentre, prospective cohort study of advanced lung cancer in Jiangsu province, China. Eligibility required patients with histologically confirmed advanced lung cancer who couldreceive treatment regimen based on camrelizumab. No other restrictive inclusion criteria were applied. Data were captured with electronic uniform database templates to ensure consistent data collection. Primary endpoint is progression-free survival (PFS), Secondary endpoints are adverse events (AE), objective response rate (ORR), disease control rate (DCR), and overall survival (OS). Results: 97 pts with advanced lung cancer were enrolled from August 7, 2019 to December 20, 2019. Median age was 64, male 82.5%, adenocarcinoma 50.5%, squamous carcinoma 29.9%, SCLC 14.4%. 30.9% were treated as first-line therapy, 24.7% were second-line treatment, 44.4% were third-line and above treatment. Treatment regimens included camrelizumab monotherapy 13.4%, combination chemotherapy 52.6%, combination anti-angiogenic therapy 24.7%. 52 pts were accessable for efficacy analysis. 11 (21%), 37(71%), and 6(8%) patients showed partial response (PR), stable disease (SD), and progression disease (PD), respectively. The ORR, DCR was 21.2%, 92.3%. 72 pts had experienced the safety assessment. This was an early stage of data analysis, PFS has not yet reached. Major AE was reactive cutaneous capillary hyperplasia (RCCEP) (20/72), no Grade≥3 RCCEP occurred. Other common AEs were eutrophil count decreased (14/72), nausea (12/72), fatigue (11/72), white blood cell decreased (10/72). No treatment-related deaths occurred. Conclusions: This Real-world research showed current treatment status of advanced lung cancer and provides preliminary evidence for camrelizumab treating with advanced lung cancer, and we expect follow-up data to provide more clues. Clinical trial information: ChiCTR1900026089.

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