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

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.

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.

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).

LCa risk is associated with diagnosis of LCa-2 in FDR to a similar degree as LCa-1 in FDRs.