PARK2 Mutation Linked to Lung Cancer Risk

Through whole-exome sequencing, researchers for the first time have identified a link between a mutation in PARK2, a gene associated with early-onset Parkinson's disease and familial lung cancer.

The findings were recently published in TheAmerican Journal of Human Genetics.

Investigators at the Medical College of Wisconsin (MCW), in collaboration with colleagues of the Genetic Epidemiology of Lung Cancer Consortium (GELCC) sequenced the exomes of individuals from a family with multiple cases of lung cancer. They then studied the PARK2 gene in additional families affected by lung cancer.

Lead study author Donghai Xiong, PhD, who is an assistant professor of pharmacology and toxicology at MCW, said this specific mutation is very rare in the general population. However, they found there was a significant association between the PARK2 mutation in the families with multiple cases of lung cancer. It is hoped this novel finding may point to new therapeutic approaches in preventing and treating familial lung cancer.

The researcher initially studied a family in which eight members across three generations developed lung cancer. They conducted whole-exome sequencing on germline DNA for three lung cancer individuals in this family. The families that were studied did not report a history of Parkinson's disease--excluding the possible confounding effect of Parkinson’s disease on the study findings.

Dr. Xiong and colleagues conducted a literature search and found an inverse association between Parkinson’s disease and spontaneous lung cancer. Recent investigations have linked two rare mutations causing alterations in proteins encoded by BRCA2 and CHEK2 that appear to have a large effect on the risk of spontaneous squamous lung cancer. However, researchers report that the effect size of PARK2 on familial lung cancer is larger than the effect sizes of the BRCA2 and CHEK2 rare variants on spontaneous lung cancer. They also note that the effect size of PARK2 on familial lung cancer was similar to the large effect of MITF on familial melanoma.

Results of this study provide an additional rationale for further investigations of this gene, and the possibility of developing targeted therapies against lung cancer in individuals with PARK2 variants.

References:

• Medical College of Wisconsin. (2015). Parkinson’s gene linked to lung cancer.