Familial risk associated with lung cancer as a second primary malignancy in first-degree relatives

Background: Aggregation of lung cancer (LCa) in family members is well-documented. However, little is known on the familial risk of LCa when first-degree relatives (FDRs, parents or siblings) are diagnosed with LCa as a second primary malignancy (LCa-2). We aimed to investigate whether and to what extent a family history of LCa-2 was associated with an increased LCa risk. Methods: In this Swedish national cohort we identified 127,865 individuals who had one FDR affected by LCa as a first primary cancer (LCa-1) and 15,490 individuals who had one FDR affected by LCa-2, respectively. We then estimated relative risk (RR) of LCa using those without cancer family history as reference. Results: The number of LCa-2 has been increasing annually and rather similarly in men and women in the last decade. Familial RR of LCa was 1.96 (95%, 1.85–2.07) for LCa-1 family history and 1.89 for LCa-2 (1.62–2.21). Risk was especially high when FDR was diagnosed with early-onset LCa-2 and when siblings were affected by LCa-2. The RR was 1.53 (1.10–2.12) when LCa-2 in FDR was diagnosed within 26 months after first primary cancer, and it increased to 2.16 (1.62–2.90) when LCa-2 was diagnosed between 74 to 154 months. Higher risk was observed for first primary cancer of the ovary (4.45, 1.85–10.7), nervous system (3.49, 1.45–8.38), upper aerodigestive tract (2.83, 1.78–4.49) and cervix (2.55, 1.41–4.61), and for non-Hodgkin lymphoma (3.13, 1.57–6.27). Conclusions: LCa risk is associated with diagnosis of LCa-2 in FDR to a similar degree as LCa-1 in FDRs.