scholarly journals Programmed Death Ligand 2 Gene Polymorphisms Are Associated With Lung Adenocarcinoma Risk in Female Never-Smokers

2021 ◽  
Vol 11 ◽  
Author(s):  
Sheng-Kai Liang ◽  
Li-Hsin Chien ◽  
Gee-Chen Chang ◽  
Ying-Huang Tsai ◽  
Wu-Chou Su ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Pulmonary Tuberculosis ◽  
Lung Adenocarcinoma ◽  
Genome Wide Association Study ◽  
Lung Cancer Screening ◽  
Tuberculosis Infection ◽  
Eqtl Analysis ◽  
Nucleotide Polymorphisms ◽  
Programmed Death ◽  
Never Smokers

ObjectivesLung cancer in never-smokers is a distinct disease associated with a different genomic landscape, pathogenesis, risk factors, and immune checkpoint inhibitor responses compared to those observed in smokers. This study aimed to identify novel single nucleotide polymorphisms (SNPs) of programmed death-1 (encoded by PDCD1) and its ligands, programmed death ligand 1 (CD274) and 2 (PDCD1LG2), associated with lung cancer risk in never-smoking women.Materials and MethodsDuring September 2002 and July 2012, we enrolled never-smoking female patients with lung adenocarcinoma (LUAD) (n=1153) and healthy women (n=1022) from six tertiary hospitals in Taiwan. SNP data were obtained and analyzed from the genome-wide association study dataset and through an imputation method. The expression quantitative trait loci (eQTL) analysis was performed in both tumor and non-tumor tissues for the correlation between genetic expression and identified SNPs.ResultsA total of 12 PDCD1LG2 SNPs related to LUAD risk were identified in never-smoking women, including rs2381282, rs4742103, rs4237162, rs4742104, rs12237624, rs78096119, rs6476988, rs7857315, rs10975178, rs7854413, rs56001683, and rs7858319. Among them, six tagged PDCD1LG2 SNPs rs2381282, rs4742103, rs4237162, rs4742104, rs78096119, and rs56001683 were significantly associated with LUAD risk. Specifically, two PDCD1LG2 SNPs, rs12237624 and rs78096119, were associated with previous pulmonary tuberculosis infection in relation to LUAD susceptibility. Through an eQTL assay, we found that rs2381282 (p < 0.001), rs12237624 (p = 0.019), and rs78096119 (p = 0.019) were associated with the expression levels of programed death ligand 2.ConclusionsNovel SNPs of programed death ligand 2 associated with lung adenocarcinoma risk were identified. Among them, two SNPs were associated with pulmonary tuberculosis infection in relation to lung adenocarcinoma susceptibility. These SNPs may help to stratify high-risk populations of never-smokers during lung cancer screening.

Germline mutations and onset of lung adenocarcinoma in smokers and nonsmokers.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 1518-1518
Author(s):  
Karen L. Reckamp ◽  
Thomas Paul Slavin ◽  
Stacy W. Gray ◽  
Carolyn E. Behrendt ◽  
Danielle Castillo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dna Repair ◽  
Cancer Screening ◽  
Lung Adenocarcinoma ◽  
Lung Cancer Screening ◽  
Germline Mutations ◽  
Age At Diagnosis ◽  
Smoking History ◽  
Younger Age ◽  
Never Smokers

1518 Background: Eligibility for lung cancer screening is based largely on pack-years of smoking, missing many cases. To propose additional groups for screening, this observational study evaluated whether germline mutations associated with cancer risk accelerate onset of lung adenocarcinoma (LA) in ever- and never-smokers. Methods: Patients with LA and family history of cancer were recruited from our oncology clinic and the Clinical Cancer Genomics Community Research Network. With consent, blood samples were screened by large multi-gene panel for 4 categories of germline mutation [lung cancer-associated genes ( TP53, EGFR); BRCA2; other genes in Fanconi anemia (FA) pathway; other DNA repair genes]. Accelerated failure-time models of age at LA diagnosis, adjusted for sex, ethnicity, and packs per day, were constructed for never-smokers and ever-smokers. Statistical significance, at p<0.05 limited the False Discovery Rate to 5% across 8 hypotheses. Results: In never-smokers with LA (n=104), mutated BRCA2, TP53 or EGFR were associated with younger age at diagnosis, while mutation in other FA or DNA repair gene was not. In ever-smokers with LA (n=65), mutated BRCA2 and other FA gene were associated with younger age at diagnosis, while other mutation categories were not (Table). Conclusions: Regardless of smoking history, BRCA2 mutation carriers experience accelerated onset of LA, as do never-smokers carrying TP53 or EGFR mutation and ever-smokers with mutation in FA gene other than BRCA2. With the exception of TP53 carriers (who merit whole body MRI), lung cancer screening with low-dose computed tomography, starting earlier in adulthood than usual, may be warranted for individuals with germline mutations in these genes. Age at Diagnosis of Lung Adenocarcinoma, by Germline Mutation and Smoking History, Adjusted for Sex, Ethnicity, and Packs per Day. [Table: see text]

Tumor mutation status of Hodgkin lymphoma survivors with secondary lung adenocarcinoma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 9600-9600
Author(s):  
David Alan Bond ◽  
Gregory Alan Otterson ◽  
Neil Dunavin
Keyword(s):  
Lung Cancer ◽  
Radiation Therapy ◽  
Lung Adenocarcinoma ◽  
Age At Diagnosis ◽  
Smoking History ◽  
Second Primary ◽  
Genomic Alterations ◽  
Number Of Patients ◽  
Never Smokers ◽  
Diagnosis Of Lung Cancer

9600 Background: In a multi-institutional, retrospective study of 1976 patients treated for Hodgkin's lymphoma (HL) from 1969-2007, 55 patients developed second primary lung cancers a median of 19.5 years after treatment. Of these 55 cases, 32 were identified as lung adenocarcinoma (ACA). The development of targeted therapies in recent years has made the detection of specific genomic alterations important for disease prognosis and treatment in lung ACA. The prevalence of certain genomic alterations (EGFR, ALK, and KRAS) is highly correlated with smoking history. We hypothesize that the prevalence of genomic alterations also may differ in patients with a significant exposure to radiation. Methods: This observational retrospective case series includes 6 patients treated with mediastinal radiation for HL who subsequently developed lung ACA. All patients were treated at Ohio State University Wexner Medical Center. Patients were identified by searching billing diagnosis codes in the electronic medical record and by query of the physicians in the department of thoracic oncology at our institution. IRB approval was obtained. Results: The average age at diagnosis of HL was 25 years (range 18-46) and the average age at diagnosis of lung cancer was 58 (range 52-73). All patients were treated with radiation therapy; two patients were treated additionally with chemotherapy. None of the patients received HDT-ASCT. The average time from diagnosis of HL to diagnosis of lung cancer was 33 years. Of our six cases, 2 were positive for EGFR mutations and the other four were triple negative (-EGFR, -ALK, -KRAS). Three were never smokers, one had a 1.5 pack year history, and two had 10 pack year histories. Lung cancer stages at diagnosis were 1B (n=2), 2B (n=1), 3A (n=2), 4 (n=1). Conclusions: To our knowledge, this is the first report of mutational status of second primary lung ACA following radiation therapy for Hodgkin disease. Although the number of patients is small, the higher prevalence of the EGFR mutation in this sample suggests that ACA related to radiation therapy may have a similar mutational profile to that of never smokers. Further investigation is needed to define the disease characteristics of lung ACA in HL survivors.

scholarly journals The Role of DNA Methylation in the Development and Progression of Lung Adenocarcinoma

2007 ◽  
Vol 23 (1-2) ◽  
pp. 5-30 ◽  
Author(s):  
Keith M. Kerr ◽  
Janice S. Galler ◽  
Jeffrey A. Hagen ◽  
Peter W. Laird ◽  
Ite A. Laird-Offringa
Keyword(s):  
United States ◽  
Lung Cancer ◽  
Dna Methylation ◽  
Lung Adenocarcinoma ◽  
Western Europe ◽  
Cpg Islands ◽  
The United States ◽  
Smoke Inhalation ◽  
Genetic Changes ◽  
Never Smokers

Lung cancer, caused by smoking in ∼87% of cases, is the leading cause of cancer death in the United States and Western Europe. Adenocarcinoma is now the most common type of lung cancer in men and women in the United States, and the histological subtype most frequently seen in never-smokers and former smokers. The increasing frequency of adenocarcinoma, which occurs more peripherally in the lung, is thought to be at least partially related to modifications in cigarette manufacturing that have led to a change in the depth of smoke inhalation. The rising incidence of lung adenocarcinoma and its lethal nature underline the importance of understanding the development and progression of this disease. Alterations in DNA methylation are recognized as key epigenetic changes in cancer, contributing to chromosomal instability through global hypomethylation, and aberrant gene expression through alterations in the methylation levels at promoter CpG islands. The identification of sequential changes in DNA methylation during progression and metastasis of lung adenocarcinoma, and the elucidation of their interplay with genetic changes, will broaden our molecular understanding of this disease, providing insights that may be applicable to the development of targeted drugs, as well as powerful markers for early detection and patient classification.

scholarly journals Low-dose CT lung cancer screening in never-smokers and smokers: results of an eight-year observational study

2020 ◽  
Vol 9 (1) ◽  
pp. 10-22 ◽  
Author(s):  
Ryutaro Kakinuma ◽  
Yukio Muramatsu ◽  
Hisao Asamura ◽  
Shun-ichi Watanabe ◽  
Masahiko Kusumoto ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Screening ◽  
Observational Study ◽  
Low Dose ◽  
Lung Cancer Screening ◽  
Low Dose Ct ◽  
Never Smokers

scholarly journals Lung cancer screening in never-smokers: facts and remaining issues

2020 ◽  
Vol 56 (5) ◽  
pp. 2002949
Author(s):  
Maurizio V. Infante ◽  
Giuseppe Cardillo
Keyword(s):  
Lung Cancer ◽  
Cancer Screening ◽  
Lung Cancer Screening ◽  
Never Smokers
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