Lung cancer risk in non-smoking females with a familial history of cancer: a multi-center prospective cohort study in China

Familial risk of lung cancer has been widely studied but whether this association holds in non-smoking females is largely unknown. We sought to determine the relationship between a family history of cancer and lung cancer risk among Chinese non-smoking females based on a multi-center prospective population-based cohort study involving 547,218 individuals between 2013 and 2019. A total of 1620 lung cancer cases occurred during a median follow-up of 3.9 years. Multivariable Cox regression showed that a family history of lung cancer in first-degree relatives significantly increased the risk of lung cancer (HR: 1.50, 95%CI: 1.29, 1.75, P<0.001). Relative to those with no relatives affected, the risk of lung cancer was 51% higher in females with one relative affected (HR: 1.51, 95%CI: 1.29-1.76, P<0.001), 123% higher in females with two relatives affected (HR: 2.23, 95%CI: 1.57-3.15, P<0.001) and 143% higher in females with three or more relatives affected (HR: 2.43, 95%CI: 1.21-4.91, P=0.013). Two nested case control studies stratified by age at diagnosis were conducted to verify potential disparities in this association between the early or late onset of lung cancer. A family history of lung cancer in first-degree relatives was significantly correlated with an elevated risk of lung cancer for both cases before and after age 65 (OR: 1.36, 95%CI: 1.07-1.74, P=0.013; OR: 1.64, 95%CI: 1.15-2.33, P=0.006). Our analysis confirmed the importance of familial history of cancers on lung cancer risk in non-smoking females and highlighted the possibility of interaction between genetic and environmental effect on lung cancer.