Pathogenic Variants in Genes Associated With Lung Adenocarcinoma

Study Overview
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Brief Summary
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The goal of this observational study is to Describe the prevalence of germ line-pathogenic variants in Mexican patients with lung adenocarcinoma. The main questions it aims to answer are: What is the prevalence of pathogenic variants in genes associated with lung adenocarcinoma in Mexican patients younger than fifty? Which clinical-pathological characteristics are associated with germ-line pathogenic variants in patients with lung adenocarcinoma? How actionable somatic mutations are associated with germ line-pathogenic variants of patients with lung adenocarcinoma? Participants will be asked to sign an informed consent; after that, they will be instructed to donate 10 ml of peripheral blood by venipuncture in the morning and before the patient has taken morning medication and the first meal, following a period of 8-12 hr fasting.

Detailed Description
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This is an observational, descriptive, and cross-sectional study. The sample size was calculated with a proportion difference formula for a known population, considering the Local Institutional Personalized Medicine Laboratory tests 100 blood samples per year from patients with non-small cell lung cancer (NSCLC). It was considered a 95% confidence level and an 80% power. In addition, a 10% loss in follow-up was estimated. After reviewing the inclusion and exclusion criteria, signing the informed consent, and peripheral blood sampling. Total DNA (tDNA) will be extracted using the DNeasy Blood & Tissue (Quiagen) kit. Likewise, for the determination of pathogenic variants, the Sophia HCS Community panels (Sophia genetics) will be used to carry out Next-generation (NGS) sequencing in a NextSeq 550 (Illumina) platform. To determine the clinical significance of genomic variants, the data analysis will be performed on the SOPHiA Alamut™ Visual Plus which is a comprehensive, full genome browser for efficient and user-friendly variant interpretation.

Official Title
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Prevalence of Pathogenic Variants (PV) in Genes That Are Related to Lung Adenocarcinoma in Mexican Patients Under the Age of 50 and Who Have Smoked.

Conditions
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Lung Adenocarcinoma

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Both sexes ≥ 18 years old histologically confirmed lung adenocarcinoma (LUAD) Signed written informed consent form A life expectancy greater than 8 weeks. Family history of Lung cancer (LC); defined as having one first-degree relative (FDR) or two or more second-degree relatives (SDR) with lung cancer, irrespective of the age at diagnosis. Diagnosis of LUAD at ≤ 50 years, or ≤60 years A pack-years index < 20. Presence of somatic driver alterations (SDA) in tumor samples. Exclusion Criteria: A sample of peripheral blood that is not accessible. Insufficient clinical pathological information in the electronic clinical record. Elimination Criteria: Withdrawal Insufficient DNA quality and concentration for genomic sequencing analyses. Lost of follow up

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS | Progression-free survival | From date of first dose administration until the date of first documented progression date or death from any cause, whichever comes first, assessed up to 100 months. | 
| OS | Overall survival | From date of first dose administration until the date of documented death from any cause or last followup, whichever comes first, assessed up to 120 months. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lung adenocarcinoma, Hereditary Cancer, Germline Pathogenic/Likely pathogenic variants, Somatic driver alterations