Association between a family history of cancer and multiple primary lung cancer risks: a population-based analysis from China

Abstract

Objectives: The incidence of multiple primary lung cancer (MPLC) has increased in recent years. The risk factors of MPLC are not well studied, especially in the Asian population. This case-control study investigated the association between a family history of cancer and MPLC risk. Methods: We used data from people who surgically confirmed MPLC with at least 2 nodes of Fujian Medical University Union Hospital and matched 1:2 normal individuals as controls between 2016 and 2017. Information on age, sex, lifestyle, personal history, and family history of cancer was collected using a self-administered questionnaire, and odds ratios (OR) were estimated using unconditional logistic regression. Results: We included 2 104 patients. In total, 321 patients with histologically confirmed MPLC and 642 healthy controls were studied. The significantly higher ratio of current smokers was observed for the cases than the controls (54.1% vs. 30.0%). A family history of LC in first-degree relatives of the cases reported a significantly higher proportion than in the controls (15.3% vs. 8.6%). Family history of all cancers and LC significantly increased the risk of MPLC (OR = 1.64, P = 0.009 and OR = 2.59, P = 0.000, respectively). The multivariate analysis identified a significantly increased risk of MPLC (OR = 2.45, P = 0.000) associated with parents and siblings influenced by LC history. The younger age (aged < 55 years) of LC cases at diagnosis exhibited a significantly increased risk of MPLC (OR = 2.39, P = 0.000). A significant association with a family history of LC was found for male squamous carcinoma and male adenocarcinoma (OR = 1.59, p = 0.037 and OR = 1.64, p = 0.032, respectively). A positive association with LC history was only observed for female adenocarcinoma (OR = 2.23, p = 0.028). The risk of MPLC was not significantly associated with A family history of cancers in non-smokers (OR = 0.91, P = 0.236). Ever-smokers with a positive family history of cancer or LC had a significantly elevated risk of MPLC (OR = 4.01, P = 0.000 and OR = 6.49, P = 0.000, respectively). We also observed a very elevated risk for smokers with no family history (OR = 3.49, P = 0.000). Such a positive association was also observed in ever-smokers with no family history of LC (OR = 3.55, P = 0.000). Adenocarcinoma in females was prevalent and significantly associated with a family history of LC in risk of MPLC compared with other histologic subtypes. Conclusions: Our findings suggest an association between a family history of LC and MPLC risk among an Asian population. Smoking status and family history of LC have a synergistic effect on MPLC. These findings indicate that MPLC exhibits familiar aggregation and that inherited genetic susceptibility may contribute to the development of MPLC.