Many people are surprised to learn that about 10 percent of all individuals with lung cancer have never smoked cigarettes. Of these "never smokers" -- defined as individuals who have smoked fewer than 100 cigarettes in their lifetime -- the majority are women who have a particular type of non-small cell lung cancer (NSCLC) called adenocarcinoma. Experts have theorized that these individuals may be genetically more susceptible to lung cancer. To help understand and identify cancer-associated genes in this group, Memorial Sloan-Kettering Cancer Center has created a blood sample registry for patients with lung cancer who have never smoked.
EGFR Mutations and Targeted Therapies
Previous research at MSKCC has shown a relatively high rate of mutations in the gene that encodes what is known as the epidermal growth factor receptor (EGFR) in lung tumors from never smokers. Specifically, the research has identified EGFR mutations in approximately 15 percent of all patients with lung adenocarcinomas, and 50 percent of patients with lung adenocarcinomas who have never smoked. NSCLCs account for about 80 percent of all lung cancers, and adenocarcinoma is the most common of three main types of NSCLC.
The targeted therapy drugs erlotinib (Tarceva™) and gefitinib (Iressa
) have been shown to halt the growth of certain types of lung cancer by zeroing in on the gene encoding EGFR. While the two drugs are effective in about 10 percent of US patients with NSCLC, they induce responses in about 75 percent of patients whose lung tumors harbor EGFR mutations.
KRAS Mutations and Never Smoker Study
Mutations in a gene called KRAS, which encodes a signaling protein activated by EGFR, were initially identified in lung cancer patients who had a history of smoking. Patients with KRAS mutations had poor prognosis after lung cancer surgery, showed no survival benefit from the use of adjuvant chemotherapy, and displayed primary resistance to both erlotinib and gefitinib.
In a study partly sponsored by the National Institutes of Health and published in the September 2008 issue [PubMed Abstract] of Clinical Cancer Research, Memorial Sloan-Kettering investigators analyzed 482 biopsy samples of lung adenocarcinomas, 81 of which were from patients who had never smoked cigarettes. While KRAS mutations were found, not surprisingly, in 25 percent of tumors from current smokers and 22 percent of tumors from former smokers, they were also found in 15 percent of tumors from never smokers. Interestingly, the type of KRAS mutation found in never smokers' tumors was genetically different from the type found in former or current smokers' tumors -- the first study to make this observation. The study's authors note that these results support further investigation of KRAS mutations, including the use of molecular testing for never smokers with NSCLC, which would help doctors to identify which patients would benefit from the use of targeted therapies like erlotinib and gefitinib.
Never Smoker Blood Sample Registry
Seeking to provide a fuller genetic understanding of never smokers, researchers at Memorial Sloan-Kettering have initiated a clinical study that will survey and collect blood samples from patients with lung cancer who have never smoked. To qualify for the free study, participants must be 18 and older, have lung cancer, and have smoked fewer than 100 cigarettes in their lifetime. Once enrolled, they are asked to fill out a short questionnaire and provide a blood sample, which can be drawn when they have routine blood tests performed at their doctor's office or at a local laboratory testing provider.
The blood samples will be used for what are known as genome-wide association studies to look for genetic differences between the genomes of never smokers with and without lung cancer. Investigators hope to be able to identify new genes, which may explain and predict why certain patients develop lung cancer without ever having smoked tobacco. This would be a critical step in establishing strategies to prevent lung cancer, to find people at high risk for the disease, and to identify new targets for therapy.
