363P Genetic predisposition for pre-invasive lung adenocarcinoma manifesting as ground-glass nodules with family history of lung cancer

e13512 Background: Lung cancer with family history have been emerging gradually of late years in East Asian, especially those presenting as pulmonary ground-glass nodules (GGNs). The predisposition of GGNs with lung cancer family history remains baffling. Methods: This prospective study was registered at clinicaltrials.gov (number NCT04220268) and enrolled patients with pulmonary pre-invasive or invasive adenocarcinoma, especially presenting as GGNs. We collected blood and tumor samples from 29 GGNs patients with family history to investigated germline and somatic mutations by whole exome sequencing (WES). As the first part of our study, we focused on 107 nonoverlapping susceptibility loci for lung carcinogenesis identified by recent genome-wide association studies (GWAS) to identify novel rare causal variants. Potential causal variants were further verified in other patients from the families when possible. Results: A total of 461267 single neocleotide variants (SNVs) and 132268 insertion-deletions (InDels) were detected from the 29 index patients. By focusing on exome profiles of the 107 target loci, we identified three key rare mutations, namely MSH5 p.Ala702Thr, ADGRG6 p.Asn338Ile and CCDC147 p.Arg619Trp in two index patients respectively. The minor allele frequency (MAF) of these three variants was extremely low in the general population, which is 1/5008, 2/5008 and 6/5008 respectively in the 1000 Genomes database, and 2/31406, 5/31346, and 5/31394 respectively in the GnomAD database. There three mutations were predicted as probably damaging or disease-causing variations by SIFT or Polyphen. Mutations of MSH5 and CCDC147 were also detected in other patients from the two families. Conclusions: With the identification of highly disruptive risk-conferring MSH5, ADGRG6 and CCDC147 mutations, we confirmed the probably heritable and risk loci exists in the GGNs patients with lung cancer family history in East Asians. Exome sequencing has great potential to identify novel rare causal variants, and more analyses on more patients are still ongoing.

Download Full-text

Value of 18F-FDG PET/CT-based radiomics model to distinguish the growth patterns of early invasive lung adenocarcinoma manifesting as ground-glass opacity nodules

EJNMMI Research ◽

10.1186/s13550-020-00668-4 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Xiaonan Shao ◽

Rong Niu ◽

Xiaoliang Shao ◽

Zhenxing Jiang ◽

Yuetao Wang

Keyword(s):

Lung Adenocarcinoma ◽

Fdg Pet ◽

Ground Glass Opacity ◽

Growth Patterns ◽

Ground Glass ◽

Pet Ct ◽

18F Fdg ◽

Invasive Lung Adenocarcinoma ◽

Fdg Pet Ct

Download Full-text

Vitamin D status and risk of type 2 diabetes in the Norwegian HUNT cohort study: does family history or genetic predisposition modify the association?

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2020-001948 ◽

2021 ◽

Vol 9 (1) ◽

pp. e001948

Author(s):

Marion Denos ◽

Xiao-Mei Mai ◽

Bjørn Olav Åsvold ◽

Elin Pettersen Sørgjerd ◽

Yue Chen ◽

...

Keyword(s):

Type 2 Diabetes ◽

Family History ◽

Genetic Predisposition ◽

Effect Modification ◽

P Value ◽

Family History Of Diabetes ◽

Increased Risk ◽

History Of

IntroductionWe sought to investigate the relationship between serum 25-hydroxyvitamin D (25(OH)D) level and the risk of type 2 diabetes mellitus (T2DM) in adults who participated in the Trøndelag Health Study (HUNT), and the possible effect modification by family history and genetic predisposition.Research design and methodsThis prospective study included 3574 diabetes-free adults at baseline who participated in the HUNT2 (1995–1997) and HUNT3 (2006–2008) surveys. Serum 25(OH)D levels were determined at baseline and classified as <50 and ≥50 nmol/L. Family history of diabetes was defined as self-reported diabetes among parents and siblings. A Polygenic Risk Score (PRS) for T2DM based on 166 single-nucleotide polymorphisms was generated. Incident T2DM was defined by self-report and/or non-fasting glucose levels greater than 11 mmol/L and serum glutamic acid decarboxylase antibody level of <0.08 antibody index at the follow-up. Multivariable logistic regression models were applied to calculate adjusted ORs with 95% CIs. Effect modification by family history or PRS was assessed by likelihood ratio test (LRT).ResultsOver 11 years of follow-up, 92 (2.6%) participants developed T2DM. A higher risk of incident T2DM was observed in participants with serum 25(OH)D level of<50 nmol/L compared with those of ≥50 nmol/L (OR 1.72, 95% CI 1.03 to 2.86). Level of 25(OH)D<50 nmol/L was associated with an increased risk of T2DM in adults without family history of diabetes (OR 3.87, 95% CI 1.62 to 9.24) but not in those with a family history (OR 0.72, 95% CI 0.32 to 1.62, p value for LRT=0.003). There was no effect modification by PRS (p value for LRT>0.23).ConclusionSerum 25(OH)D<50 nmol/L was associated with an increased risk of T2DM in Norwegian adults. The inverse association was modified by family history of diabetes but not by genetic predisposition to T2DM.

Download Full-text

Diffuse Cystic Metastases in the Lung after Nivolumab Treatment in a Patient with Non-Small Cell Lung Cancer: A Case Report

Case Reports in Oncology ◽

10.1159/000513426 ◽

2021 ◽

pp. 34-38

Author(s):

Satoshi Muto ◽

Yuki Ozaki ◽

Takuya Inoue ◽

Naoyuki Okabe ◽

Yuki Matsumura ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Lung Metastases ◽

Sialyl Lewis X ◽

Ground Glass ◽

Cystic Lesions ◽

Positron Emission ◽

Ground Glass Nodules

Although diffuse cysts in the lung can be found in many diseases, they are uncommon in metastatic lung adenocarcinoma. They are even more unusual after the administration of immune checkpoint inhibitors. A case of lung adenocarcinoma that developed diffuse cysts in the lungs during treatment with nivolumab is reported. The patient was a 60-year-old woman with postoperative recurrent lung adenocarcinoma in mediastinal lymph nodes and pleural dissemination. After first-line treatment with cisplatin, pemetrexed, and bevacizumab, computed tomography (CT) showed disease progression. Treatment was then switched to nivolumab. After 5 courses of nivolumab, CT showed multiple ground-glass nodules in her lungs. After 4 more courses of nivolumab, the ground-glass nodules increased in size, and cystic air spaces appeared in their centers. The patient did not have any symptoms. Laboratory tests showed no evidence of infection or nivolumab-induced pneumonitis. Sialyl Lewis X-i antigen increased, and positron emission tomography showed abnormal uptake of 18F-fluorodeoxyglucose in these lesions. Considering this evidence, the cystic lesions were diagnosed as multiple lung metastases. Various differential diagnoses should be considered when diffuse cystic lesions are found in the lungs after the administration of immune checkpoint inhibitors.

Download Full-text

Combined Effects of Lung Disease History, Environmental Exposures, and Family History of Lung Cancer to Susceptibility of Lung Cancer in Chinese Non-smokers

10.21203/rs.3.rs-389632/v1 ◽

2021 ◽

Author(s):

Fanglin Yu ◽

Rendong Xiao ◽

Xu Li ◽

Zhijian Hu ◽

Lin Cai ◽

...

Keyword(s):

Lung Cancer ◽

Family History ◽

Environmental Factors ◽

Lung Disease ◽

Environmental Exposures ◽

Collective Effects ◽

Combined Effects ◽

Cancer History ◽

Increased Risk ◽

History Of

Abstract Background: Although cigarette smoking is a major risk factor for lung cancer, the incidence rate of lung cancer among non-smokers is notable. The etiology and potential mechanism of non-smoker lung cancer are worthy of further research. This study was designed to explore the collective effects of environmental factors and the relationship between environmental exposure index (EEI) and lung cancer among non-smokers by evaluating the joint effects among lung disease history, environmental factors, and family history of lung cancer without smoking confounders.Methods: A total of 767 never-smoked lung cancer cases and 767 sex- and age-matched controls were selected from the department of Thoracic Surgery and Respiratory Medicine of three hospitals in Fujian, China. We used two methods to develop the EEI according to 12 statistically significant environmental risk factors. Restricted cubic spline (RCS) was applied to analyze the non-linear relationship between EEI and lung cancer in non-smokers. Combined effects, additive interaction, and multiplicative interaction were assessed among lung disease history, EEI, and family history of lung cancer to estimate susceptibility to develop lung cancer.Results: Lung disease history, especially asthma, was significantly associated with an increased risk of lung cancer with an odds ratio (OR) for asthma history of 14.720 (95% CI: 1.877–115.449). Family history of lung cancer was related to susceptibility of lung cancer (OR = 3.347, 95% CI: 1.930–5.806). According to type of relatives and cancer, a parental or children’s history and a sibling’s history of lung cancer were significantly associated with an increased risk of lung cancer. The positive association between EEI and lung cancer was apparently stronger in those with lung disease history or family lung cancer history. Furthermore, there was a addictive interaction between EEI and lung disease history, and a possibly addictive interaction between EEI and family lung cancer history on development of lung cancer.Conclusions: There were combined effects among lung disease history, environmental exposures, and family history of lung cancer toward susceptibility to lung cancer in Chinese non-smokers. Non-smokers who had a family history of lung cancer were at higher risk of lung cancer than non-smokers who had lung disease history. Non-smokers with family cancer history may obtain benefits from removal of environmental exposures and active treatment of lung disease.

Download Full-text