In a new study entitled “A Recurrent Mutation in PARK2 Is Associated with Familial Lung Cancer” a team of researchers found that a germline mutation in a gene associated with Parkinson’s disease, Park2, confers genetic susceptibility to lung cancer. The study was published in the American Journal of Human Genetics.
Lung cancer is the deadliest cancer in the United States. According to data from the Centers for Disease Control and Prevention, in 2011 alone, 207,339 people were diagnosed with lung cancer with 156,953 confirmed deaths – 86,736 and 70,217 of those occurring in men and women, respectively.
Genetic susceptibility factors associated with environmental risks, such as smoking, increase lung cancer incidence. Notably, while large-scale studies found germline genetic variations associated with lung cancer susceptibility, there is lack of knowledge on variants within familial lung cancer.
In this study, a team of researchers from the Medical College of Wisconsin and the Genetic Epidemiology of Lung Cancer Consortium (GELCC) performed an exome sequencing (a technique to sequence all protein-coding genes in a specific genome) on a family affected by lung cancer. The authors identified a germline mutation (i.e., a variation in DNA sequencing found in germ cells and therefore transmitted to offsprings) in the Park2 gene, usually associated with Parkinson’s disease, but whose functions can greatly vary. Moreover, the authors observed that mutations in Park2 increase the proliferation capacity of lung cancer cells, suggesting this gene as a possible candidate associated with lung cancer risk.
These data demonstrate that the identified Park2 germline mutation increases carriers’ susceptibility to develop lung cancer. Therefore, additional studies are necessary to understand the function of this gene and mutation in the context of lung cancer. Furthermore, there is a need to find additional mutations that also increase the susceptibility of developing this malignancy. These findings are crucial towards the development of novel therapeutic strategies for lung cancer patients positive for Park2 mutations.
Donghai Xiong, PhD, assistant professor of pharmacology and toxicology at MCW and study’s first author commented in a press release, “While this specific mutation is very rare in the general population, there was a significant association between the PARK2 mutation we studied and the families with multiple cases of lung cancer.”
Ming You, MD, PhD, the Joseph F. Heil Jr. Professor of Oncogenesis at MCW and Director of the MCW Cancer Center and study leading author added, “These results implicate this specific mutation as a genetic susceptibility factor for lung cancer, and provide an additional rationale for further investigations of this gene and this mutation for evaluation of the possibility of developing targeted therapies against lung cancer in individuals with PARK2 variants.”