Objective To explore risk factors for lung cancer among non-smoking women by using the random forest method, and provide a reference for preventing lung cancer among non-smoking women.

Methods From August 2017 to August 2021, a hospital-based multicenter case-control study was conducted, involving 1 315 participants from Liaoning, Jiangsu, Anhui, and Qinghai province, with 679 non-smoking women with newly diagnosed lung cancer at tertiary or higher-level hospitals in the case group and 636 non-cancer female patients or healthy women who sought care or underwent physical examination at the same hospitals in the control group. A revised questionnaire based on Female Lung Cancer Consortium in Asia and Xuanwei Female Lung Cancer Questionnaire was adopted to collect information on demography, exposure factors, behavioral factors, past history and family history. The random forest model and multivariate logistic regression analysis were used to analyze risk factors for lung cancer among non-smoking women.

Results A total of 1 294 female participants were finally included in analysis. There was no significant difference in age, nation, and education level (P>0.05) between the case group (n=668) and the control group (n=626). After running 10-fold cross-validation 5 times, the random forest analysis showed that the following ten factors were the main risk factors for lung cancer in non-smoking women: passive smoking, living on the ground floor or in the basement for at least 20 years, the presence of a smelter plant near residence for at least 20 years, a history of chronic bronchitis, maternal smoking during pregnancy, a family history of lung cancer of first-degree relatives, a history of pneumonia, and occupational exposure to radiation, pesticides, or other chemicals for at least 10 years. The logistic regression analysis showed that passive smoking (OR: 1.42, 95%CI: 1.07-1.89), living on the ground floor or in the basement for at least 20 years (OR: 1.56, 95%CI: 1.17-2.10), and the presence of a smelter plant within 5 km around residence for at least 20 years (OR: 2.27, 95%CI: 1.19-4.56) were the risk factors for lung cancer among non-smoking women; a family history of lung cancer of first-degree relatives, a history of pneumonia and occupational exposure to chemicals for at least 10 years were marginally associated with the risk of lung cancer among non-smoking women (P < 0.10).

Conclusion Besides exposure to indoor and outdoor air pollution, pneumonia and occupational exposure to chemicals may also be risk factors for lung cancer in non-smoking women.