inherit egfr - studying germline egfr mutations

Conditions: Lung Cancer

Summary: 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.

if a subject have lung cancer or another cancer carrying a t790m mutation in the egfr gene, he/she may be eligible to participate in this research study. to determine eligibility, a subject will need to perform the following steps: provide informed consent, fill out the study questionnaire and provide medical records documentation. the study questionnaire should take about 30 minutes to complete. the questionnaire asks for information on personal and family cancer and health history. the information provided will help investigators to determine which parts of the study a subject is eligible for. a few weeks after submitting the questionnaire, a member of the research study team will contact the subject by telephone to clarify any questions about the response. for medical records documentation investigators will request permission to obtain and review medical records pertaining to any personal history of cancer. subjects will need to complete a medical record release form to allow investigators to collect medical records regarding prior cancers and cancer treatment. after a subject is determined to be eligible, he/she will have a conversation with a genetic counselor regarding the potential risks, benefits and limitations of genetic testing. a genetic counselor is an expert in the field of inherited disorders. they work as members of the health care team and act as a patient advocate providing education and support to the patient, family and the medical team. if a subject agrees to proceed, he/she will be provided a kit (by mail or in person) to provide a saliva sample for genetic testing. this involves spitting into a special container provided by the study. this sample will be sent to a clinically-certified testing laboratory to determine presence of an inherited egfr mutation. once the results have been determined, the subject will receive a letter with the phone number of a genetic counselor to call in order to review results of the genetic testing. alternatively, a subject can decide not to receive the results of the genetic testing and can note that on the letter received and send it back to the study team instead of calling for the results. if a mutation is found in the saliva sample, a subject will receive information about how to undergo confirmatory testing of a blood specimen. this can be done at a local laboratory using a kit that will be mailed. when the results are available a genetic counselor will call to discuss them. if the confirmatory blood test confirms an inherited mutation, subjects will receive instructions on how to invite family members to be tested if appropriate. investigators will collect material from a prior tumor biopsy (if available), copies of imaging scans, and medical records to study. the copies of imaging scans will allow study of the characteristics of nodules in the lungs. this information will be used to answer additional questions about cancers carrying egfr t790m mutations. it will only take a few months to complete the main part of the study. after that, subjects will be followed every 6 months for 2 years. if a subject allows a piece of a tumor specimen or dna to be stored for future investigational studies, then he/she will remain enrolled in research for as long as the specimen is stored in the specimen bank.

Eligibility criteria:
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

Keywords: gene mutation