Smokers With Emphysema Linked to TERT Mutation

Smokers With Emphysema Linked to TERT Mutation

shutterstock_196890071Among the millions of individuals with lung cancer, a number of patients who smoke also have emphysema, which may potentially be a result of mutations in the gene that encodes for telomerase reverse transcriptase (TERT). This protein, which helps maintain the telomere caps on the ends of DNA, was the subject of a recent publication in Journal of Clinical Investigation that associated TERT mutations with emphysema.

Researchers at Johns Hopkins Kimmel Cancer Center headed the research entitled “Telomerase Mutations in Smokers with Severe Emphysema.” The team was motivated by a conundrum described by principal investigator Mary Armanios, MD, in a news release from the Cancer Center: “Not everyone who smokes gets emphysema, so our study is part of a bigger effort to find out why some people get it and others do not.”

Similarly, only 10% of individuals who smoke are diagnosed with chronic obstructive pulmonary disease (COPD), another disease common among lung cancer patients. Dr. Armanios and the rest of her team gathered genetic data from studies funded by the National Institutes of Health that concerned patients with COPD. In a sample of 292 severe COPD patients who smoked, three patients (1%) carried a mutation in the gene for TERT.

Although 1% is a small proportion of the population, it is the same magnitude as the proportion of patients with a mutation in the alpha-1 antitrypsin gene that is accepted as a genetic risk factor for COPD. Additionally, only two TERT mutations were investigated, and Dr. Armanios believes, “There are many genes that regulate the telomere, so it’s likely that more than 1% could be impacted by these predisposing factors.”

Looking further, the team identified 50 patients (39 nonsmokers and 11 smokers) at Johns Hopkins who had syndromes associated with telomere shortening. None of the nonsmokers had emphysema, while seven smokers had emphysema. Notably, all six female smokers had emphysema, suggesting that female smokers carrying TERT mutations are more susceptible to this condition, according to Dr. Armanios.

Further, a number of previous studies have also suggested that young female smokers tend to acquire emphysema more readily. “[This study] may now give us an explanation for why people with emphysema have these systemic problems,” stated Dr. Armanios. “If we know that they have a telomerase mutation, it may help us take care of them in a more sophisticated way and delay the onset of those diseases.” Among these diseases, idiopathic pulmonary fibrosis is often associated with telomerase mutations, which may have negative implications for an individual receiving a lung transplant to correct a debilitating disease such as lung cancer.

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