Rare Variant Increases Lung Cancer Risk

While smoking is a well-established cause of lung cancer, studies have shown that approximately 20 percent of lung cancer patients have never smoked and that roughly 15 percent of smokers actually develop the disease.

Family history is believed to play a prominent role. Zeynep H. Gümüş, PhD, Assistant Professor of Genetics and Genomic Sciences, Icahn Institute for Data Science and Genomic Technology at Mount Sinai, has committed her research to uncovering the genetic link. By conducting the largest population-based study, to date, on germ-line whole-exome sequencing datasets, Dr. Gümüş has identified a rare, deleterious variant in the ATM gene that can predispose individuals to increased risk of lung adenocarcinoma (LUAD).

Lung cancer is the leading cause of cancer deaths in the world, and LUAD is its most prevalent subtype. In a paper published August 27, 2020, in the Journal of Thoracic Oncology, Dr. Gümüş and her research team also reported that ATM is a recognized risk gene for cancers of the pancreas, breast, and prostate, suggesting that LUAD may be part of an ATM-related cancer syndrome with important implications for surveillance, early detection, and chemotherapeutic intervention.

“We know the odds of surviving lung cancer are much higher when it’s detected at Stage I, which would allow individuals known to have ATM variants to benefit from increased surveillance, particularly low-dose CT screening,” says Dr. Gümüş. “This regimen could be particularly important for young adults with the mutation who may have never smoked and, therefore, would not have been screened. Having this information could be a life-saver for them.”

The same health benefits could be realized by another high-risk group identified by Dr. Gümüş and her Mount Sinai research team. This cohort carries rare, pathogenic variants in Franconi anemia genes, which are risk factors for lung squamous cell carcinoma. Dr. Gümüş is hopeful these findings, like those for lung adenocarcinoma, will also lead to the development of a genetic diagnostic test for early detection and preventive treatment.