Germline mutations and age at onset of lung adenocarcinoma

Cancer ◽  
2021 ◽  
Author(s):  
Karen L. Reckamp ◽  
Carolyn E. Behrendt ◽  
Thomas P. Slavin ◽  
Stacy W. Gray ◽  
Danielle K. Castillo ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Age At Onset ◽  
Germline Mutations

Contribution of germline mutations to PARK2 gene inactivation in lung adenocarcinoma

2012 ◽  
Vol 51 (5) ◽  
pp. 462-472 ◽  
Author(s):  
Reika Iwakawa ◽  
Hirokazu Okayama ◽  
Takashi Kohno ◽  
Aiko Sato-Otsubo ◽  
Seishi Ogawa ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Germline Mutations ◽  
Gene Inactivation

Oligogenic germline mutations identified in early non-smokers lung adenocarcinoma patients

Lung Cancer ◽  
2014 ◽  
Vol 85 (2) ◽  
pp. 168-174 ◽  
Author(s):  
Alessandra Renieri ◽  
Maria Antonietta Mencarelli ◽  
Francesco Cetta ◽  
Margherita Baldassarri ◽  
Francesca Mari ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Germline Mutations

scholarly journals Aetiology of MDS: With a Focus on Hereditary Predisposition

Hemato ◽  
2021 ◽  
Vol 3 (1) ◽  
pp. 17-37
Author(s):  
Anjum B. Khan ◽  
David Bowen
Keyword(s):  
Age At Onset ◽  
Later Life ◽  
Germline Mutations ◽  
Minor Role ◽  
Age Group ◽  
Biological Factors ◽  
Age Related ◽  
Hereditary Disorders ◽  
A Minor ◽  
Eighth Decade

Myelodysplastic syndromes affect an older age group with a median age at onset in the eighth decade of life. As such, there is a relationship between the pathogenesis of MDS and age-related processes affecting haematopoietic stem/progenitor cells and/or the bone marrow microenvironment. MDS with an onset in younger people may be associated with recognised hereditary myeloid malignancy syndromes, and ‘forme fruste’ presentations of inherited syndromes in later life are now increasingly recognised such as germline mutations in DDX41. The considerable clinical and research interest in hereditary disorders is reflected in the relative emphasis within our manuscript. Prior chemo/radiotherapy is a clear cause of MDS but the predisposition factors for therapy-related MDS remain unclear. Clonal haematopoiesis is common in older people and may evolve to MDS, although once again, the biological factors driving this evolution are largely unknown. Finally, environmental exposure to genotoxic agents is likely to play only a minor role in the contemporary occupational/recreational setting.

scholarly journals Germline Mutations in DNA Repair Genes in Lung Adenocarcinoma

2017 ◽  
Vol 12 (11) ◽  
pp. 1673-1678 ◽  
Author(s):  
Erin M. Parry ◽  
Dustin L. Gable ◽  
Susan E. Stanley ◽  
Sara E. Khalil ◽  
Valentin Antonescu ◽  
...  
Keyword(s):  
Dna Repair ◽  
Lung Adenocarcinoma ◽  
Germline Mutations ◽  
Dna Repair Genes ◽  
Repair Genes

scholarly journals Overview on population screening for carriers with germline mutations in mismatch repair (MMR) genes in China

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Min Zhang ◽  
Tianhui Chen
Keyword(s):  
Early Detection ◽  
Mismatch Repair ◽  
Genome Stability ◽  
Genome Instability ◽  
Age At Onset ◽  
Germline Mutations ◽  
Population Screening ◽  
Mmr Genes ◽  
Gene Testing ◽  
Mutation Carriers

AbstractDNA mismatch repair (MMR) genes play an important role in maintaining genome stability. Germline mutations in MMR genes disrupt the mismatch repair function and cause genome instability. Carriers with MMR germline mutations are more likely to have MMR deficiency and microsatellite instability (MSI) than non-carriers and are prone to develop colorectal cancer (CRC) and extracolorectal malignancies, known as Lynch syndrome (LS). MMR gene testing for suspected mutation carriers is a reliable method to identify the mutation types and to discover mutation carriers. Given that carriers of MMR germline mutations have a higher risk of LS-related cancers (LS-RC) and a younger age at onset than non-carriers, early surveillance and regular screening of relevant organs of carriers are very important for early detection of related cancers. This review mainly focuses on the general status of MMR carriers, the approaches for early detection and screening, and the surveillance of MMR mutation carriers in China. Population screening of MMR germline mutation carriers in China will be helpful for early detection, early diagnosis and treatment of MMR mutation carriers, which may improve the 5-year survival, and reduce mortality and incidence rate in the long term.

Novel Germline Mutation in BCAR1 in Two Siblings With Lung Cancer: a Possible Susceptibility Gene

2020 ◽  
Author(s):  
Zhu Kuikui ◽  
Zhao Yangchao ◽  
Wu Lu ◽  
Zhang Sijia ◽  
Zong Yan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Squamous Cell Carcinoma ◽  
Lung Adenocarcinoma ◽  
Somatic Mutations ◽  
Susceptibility Gene ◽  
Genetic Diagnosis ◽  
Lung Squamous Cell Carcinoma ◽  
Germline Mutations ◽  
Causative Mechanism ◽  
Functional Analyses

Abstract Background: Lung cancer is the most prevalent malignancy worldwide. Most patients were sporadic and carried somatic mutations in hotspot genes. At present, accumulating researches had identified several germline mutations that predispose patients to lung cancer. In this report, two siblings were diagnosed as lung squamous cell carcinoma and lung adenocarcinoma, respectively. Results: The two siblings shared similar features of a germline insertion of 11 bp (GCCCTGGCATT) in BCAR1 producing a frameshift at codon 314 which is located at the substrate domain. The BCAR1 was previously demonstrated to be associated with lung cancer. The variant detected in this report would impair the regulation and functions of BRCA1 in some extent, thus may promote lung cancer tumorigenesis. Our findings suggest that BCAR1 is a possible susceptibility gene for lung cancer, and its functional analyses in lung cancer need further investigation.Conclusions: In this study, we first reported a novel causative mechanism of Lung cancer: an insertion of 11 bp in BCAR1 gene, which can be helpful in the genetic diagnosis of this disease.

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]

scholarly journals Identification of Germline Mutations in Melanoma Patients with Early Onset, Double Primary Tumors, or Family Cancer History by NGS Analysis of 217 Genes

Biomedicines ◽  
2020 ◽  
Vol 8 (10) ◽  
pp. 404
Author(s):  
Lenka Stolarova ◽  
Sandra Jelinkova ◽  
Radka Storchova ◽  
Eva Machackova ◽  
Petra Zemankova ◽  
...  
Keyword(s):  
Age At Onset ◽  
Primary Melanoma ◽  
Germline Mutations ◽  
Cancer Syndrome ◽  
Melanoma Risk ◽  
Cancer History ◽  
Primary Tumors ◽  
Risk Genes ◽  
Increased Risk ◽  
Melanoma Patients

Cutaneous melanoma is the deadliest skin malignity with a rising prevalence worldwide. Patients carrying germline mutations in melanoma-susceptibility genes face an increased risk of melanoma and other cancers. To assess the spectrum of germline variants, we analyzed 264 Czech melanoma patients indicated for testing due to early melanoma (at <25 years) or the presence of multiple primary melanoma/melanoma and other cancer in their personal and/or family history. All patients were analyzed by panel next-generation sequencing targeting 217 genes in four groups: high-to-moderate melanoma risk genes, low melanoma risk genes, cancer syndrome genes, and other genes with an uncertain melanoma risk. Population frequencies were assessed in 1479 population-matched controls. Selected POT1 and CHEK2 variants were characterized by functional assays. Mutations in clinically relevant genes were significantly more frequent in melanoma patients than in controls (31/264; 11.7% vs. 58/1479; 3.9%; p = 2.0 × 10−6). A total of 9 patients (3.4%) carried mutations in high-to-moderate melanoma risk genes (CDKN2A, POT1, ACD) and 22 (8.3%) patients in other cancer syndrome genes (NBN, BRCA1/2, CHEK2, ATM, WRN, RB1). Mutations in high-to-moderate melanoma risk genes (OR = 52.2; 95%CI 6.6–413.1; p = 3.2 × 10−7) and in other cancer syndrome genes (OR = 2.3; 95%CI 1.4–3.8; p = 0.003) were significantly associated with melanoma risk. We found an increased potential to carry these mutations (OR = 2.9; 95%CI 1.2–6.8) in patients with double primary melanoma, melanoma and other primary cancer, but not in patients with early age at onset. The analysis revealed affected genes in Czech melanoma patients and identified individuals who may benefit from genetic testing and future surveillance management of mutation carriers.

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