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Gregory J. Riely, MD, PhD
Gregory J. Riely, MD, PhD
Germline variants play a significant role in lung cancer risk, particularly non-small cell lung cancer, according to a new study results published in JCO Precision Oncology. In individuals without a history of smoking, the MUTYH gene—typically linked to colorectal and other gastrointestinal malignancies—may warrant further investigation, according to Matthew R. Trendowski, MD, PhD, of the University of Michigan, and colleagues.
They used the ClinVar database to look at DNA damage response (DDR) in cases of lung cancer in non-Hispanic White and African American patients. Among 67 DDR genes, 49 unique rare pathogenic variants were found in 21 genes. Of 156 carriers, 5.9% of lung cancer cases and 4.2% of controls carried at least one variant, with variants more common in adenocarcinoma (odds ratio [OR], 1.46 [95% CI, 1.00 to 2.14]). The associations between MUTYH germline variants were most prominently seen in patients who never smoked (OR, 3.37 [95% CI, 1.08 to 10.26]), as well as in those who did not meet current United States Preventive Services Task Force lung cancer screening criteria (OR, 2.85 [95% CI, 1.20 to 7.53]).
“Although lung cancer is one of the most common malignancies and has the highest risk of cancer-related mortality, the underlying genetics contributing to susceptibility remain poorly understood,” the study authors explained. “We demonstrated association between carriers and lung cancer, providing evidence that rare variants within DNA damage pathways may increase susceptibility to lung cancer, regardless of age, sex, packyears, or race.”
Disclosure: For full disclosures of the study authors, visit ascopubs.org.
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