Smoking is widely known as the leading risk factor for lung cancer, the top cause of cancer deaths in South Korea. But as cases emerge among non-smokers and younger patients, questions have grown about genetic predispositions that environmental factors alone cannot explain. A new meta-analysis found that roughly eight in every 100 lung cancer patients carry an inherited genetic variant that may contribute to the disease.
A joint research team analyzed the overall and gene-specific prevalence of germline pathogenic or likely pathogenic variants and related factors by pooling 28 lung cancer studies, medical industry sources said on the 13th. The team included Professor Lee Ji-young of the Department of Radiology at Seoul National University Hospital, Professor Kim Si-hyun of the Department of Clinical Genomic Medicine, Professor Na Kwon-joong of the Department of Thoracic and Cardiovascular Surgery, Professor Goo Jin-mo of the Department of Radiology, and Professor Yoon Soon-ho of the Department of Radiology at National Jewish Health.
The prevalence of such variants among all lung cancer patients was 7.9%, with mutations concentrated in genes involved in DNA damage repair. By gene, BRCA2 was the most common at 0.96%, followed by ATM at 0.67%, TP53 at 0.57%, CHEK2 at 0.49% and BRCA1 at 0.48%.
Among high-risk patients screened on the basis of a family history of lung cancer, early onset or multiple primary lung cancers, prevalence reached 32.3% — significantly higher than the 4.7% found in the general lung cancer patient group. The analysis also showed that prevalence of pathogenic variants tended to be higher when the average age of the patient group was lower and when more genes were tested.
Differences in overall prevalence by genetic background were not statistically significant, but variants in major DNA damage repair genes appeared more frequently in non-Asian and mixed-race populations than in East Asians.
"This study found a high prevalence of germline pathogenic variants in patients with high-risk characteristics such as a family history or early onset," Lee said. "It could help with cancer prevention and early diagnosis for patients and their families."
Kim said genetic predispositions such as BRCA1 and BRCA2 mutations are well established in breast and ovarian cancer, but the distribution and characteristics of genetic factors in lung cancer have been relatively poorly understood. "The significance lies in systematically presenting the genetic predispositions for lung cancer," Kim said. The findings were published in the online edition of the Journal of Thoracic Oncology, an international academic journal.
