A mutational signature of non-smoking female lung adenocarcinoma in Taiwan
Lung adenocarcinoma (LUAD) is the leading cause of cancer-related mortality worldwide. While lung tumorigenesis is frequently associated with non-genetic risk factors, such as tobacco smoking, the majority of Asian female LUAD patients are non-smokers. Notably, many people are chronically exposed to cooking oil fumes (COFs) from traditional cooking practices, suggesting a potential environmental carcinogen. This study aimed to identify distinct somatic mutation signatures associated with COFs exposure by comparing 17 non-smoking female LUAD patients (aged 20-75) with documented COFs exposure recruited from Kaohsiung Medical University Hospital (KMUH), Taiwan (2019-2021), and 37 non-smoking female LUAD patients of the same age range from The Cancer Genome Atlas (TCGA). Whole-exome sequencing was performed on the KMUH cohort to assess genomic alterations. We found that 14 of the 17 KMUH cases exhibited the SBS15 signature, which was absent in all TCGA cases (0/37; p = 2.1 × 10-10; false discovery rates q = 1.7 × 10??). SBS15 is associated with defective DNA mismatch repair and microsatellite instability. These findings suggest that SBS15 is a potential biomarker for LUAD among Asian non-smoking females and underscore the importance of incorporating environmental exposures, such as COFs, into risk assessment, early detection, and precision cancer prevention strategies.