INHERIT EGFR - Studying Germline EGFR Mutations

Lung cancer is a common malignancy that is associated with cigarette smoking but can also affect individuals who never smoked. It is not well understood whether there are hereditary risk factors that influence the risk of lung cancer. It has been recently found that a small number of families have an inherited (passed from parent to child) change in one of their genes that may contribute to an increased tendency to develop lung cancers, even in never smokers. In some lung cancer patients this gene, called "EGFR", contains a DNA change known as an "inherited EGFR mutation". Early data indicate that these inherited EGFR mutations may be associated with an increased risk of lung cancer. So far, only a small number of families have been found to carry inherited EGFR mutations. For this reason the risk of lung cancer associated with inherited EGFR mutations is not well understood. Understanding the risk may help investigators find ways of detecting lung cancer sooner or reducing the risk of developing lung cancer. It was recently discovered that lung cancer patients who are found to carry one rare EGFR mutation in their cancer cells, called "T790M", have an increased risk of carrying an inherited EGFR mutation in their normal cells as well. This represents a new strategy for finding individuals and families carrying inherited EGFR mutations. This research study is designed to find cancer patients whose tumors have this EGFR mutation, T790M, to find out if they also have an inherited EGFR mutation. Subjects will not have to undergo a biopsy to participate in this research study. Investigators will collect a saliva specimen from patients with a T790M in their cancer to find out if they also have an inherited EGFR mutation. Study participants found or known to carry an inherited EGFR mutation will have the option of offering their close relative the opportunity to also participate in this study. Close relatives can consider testing to see if they also carry the inherited mutation in their normal cells. Once investigators have identified individuals and relatives that carry inherited EGFR mutations in their genes, investigators will then try to understand the risk of lung cancer and other cancers. Individuals with inherited EGFR mutations will also have the opportunity to participate in future studies related to cancer and other diseases. This study is being funded in part by the Conquer Cancer Foundation of ASCO and the Bonnie J. Addario Lung Cancer Foundation.

Sex

All

Minimum age

18 Years

Inclusion Criteria:

To participate in this study a subject must meet the eligibility of one of the following cohorts:

Cohort 1 - Cancer patients with T790M in their tumor must both:

* Have a diagnosis of cancer of any type (lung cancer or other)
* Have an EGFR mutation identified. Either EGFR T790M identified on tumor genotyping of their cancer OR on quantitative plasma genotyping with evidence of high level (\>40% allelic fraction) EGFR T790M OR
* Another EGFR mutation previously reported as germline detected on tumor genotyping of their cancer

Cohort 2 - Relatives of carriers of germline EGFR mutations are eligible as follows:

* First-degree or second-degree relatives of an individual known to carry a germline EGFR mutation (either T790M or other novel germline EGFR mutation)
* Third-degree relatives of an individual known to carry a germline EGFR mutation (either T790M or other novel germline EGFR mutation) if the relative has a personal history of lung cancer or another malignancy

Cohort 3 - Individuals already known to carry a germline EGFR mutation must:

* Have a known germline EGFR mutation (either T790M or other novel germline EGFR mutation)

Exclusion Criteria:

* Subjects with lung cancer and an acquired T790M mutation first detected after exposure to an EGFR tyrosine kinase inhibitor such as erlotinib or gefitinib
* Subjects who are too ill to complete the study questionnaire or provide the necessary specimen for testing
* Subjects who are unable to give informed consent
* Subjects who are unable to speak or read English or Brazilian Portuguese
* Subjects under the age of 18

• BACKGROUNDOxnard GR, Miller VA, Robson ME, Azzoli CG, Pao W, Ladanyi M, Arcila ME. Screening for germline EGFR T790M mutations through lung cancer genotyping. J Thorac Oncol. 2012 Jun;7(6):1049-52. doi: 10.1097/JTO.0b013e318250ed9d. PMID 22588155
• DERIVEDOxnard GR, Chen R, Pharr JC, Koeller DR, Bertram AA, Dahlberg SE, Rainville I, Shane-Carson K, Taylor KA, Sable-Hunt A, Sholl LM, Teerlink CC, Thomas A, Cannon-Albright LA, Fay AP, Ashton-Prolla P, Yang H, Salvatore MM, Addario BJ, Janne PA, Carbone DP, Wiesner GL, Garber JE. Germline EGFR Mutations and Familial Lung Cancer. J Clin Oncol. 2023 Dec 1;41(34):5274-5284. doi: 10.1200/JCO.23.01372. Epub 2023 Oct 23. PMID 37579253