The clinical impact of family history of cancer in female never-smoker lung adenocarcinoma

Abstract

Objectives: Accumulating evidence reveals the association between the risk of never-smoker lung cancer and family history of cancer. However, the clinicogenomic effect of family history of cancer in never-smoker lung cancer remains unknown.

Material and methods: We screened 3,241 lung cancer patients who (a) underwent curative resection at National Cancer Center (Goyang, Korea) between 2001-2014, and (b) completed a pre-designed interview about family/smoking history at the time of diagnosis and identified 604 female never smoker lung adenocarcinoma. A positive family history of cancer [categorized as pulmonary cancer (FH-PC) or non-pulmonary cancer (FH-NPC)] was defined as a self-reported history of cancer in first-degree relatives. Survival data were followed up until January 2017. Multiplexed targeted next-generation sequencing was performed for genetic profiling.

Results: Of 604 patients, 29.1% (n = 176) had a FH, including 132 (21.9%) with FH-NPC and 44 (7.3%) with FH-PC. Patients with the FH-NPC had a higher proportion of young patients (≤45 years) than those without the FH-NPC (FH-NPC, FH-PC, and no FH; 13.6%, 2.3%, and 8.2%, respectively; P = 0.032). Patients with the FH-NPC had an increased risk of recurrence (hazard ratio [HR]: 1.90; 95% confidence interval [CI]: 1.40-2.56; P<0.001) and death (HR: 1.67; 95% CI: 1.18-2.37; P=0.004). In contrast, the FH-PC had no prognostic effect on recurrence (HR: 1.23; 95% CI: 0.71-2.15; P = 0.456) and death (HR: 0.93; 95% CI: 0.45-1.91; P=0.838). Among three driver oncogene alterations, EGFR mutation was significantly associated with the FH-PC (53.8%, 84.1%, and 65.8%, respectively; P = 0.016), ALK/ROS1/RET fusions was significantly associated with the FH-NPC (13.7%, 0.0%, and 5.0%, respectively; P = 0.004), but KRAS mutation was not associated with any type of the FH (13.8% vs. 6.0% vs. 7.8%, respectively; P = 0.288).

Conclusion: The type of family history of cancer was associated with distinct clinocogenomic subtypes and prognosis of never-smoker lung adenocarcinoma.

Keywords: ALK; EGFR; Family history; Never smoker; Non-small-cell lung cancer; Prognosis.