Second Primary Lung Cancer Associated With Family History of Lung Cancer

Familial clustering of initial primary lung cancer (IPLC) may be related to shared smoking habits, other environmental exposures and hereditary factors, but whether familial risk also influences the risk of second primary LC (SPLC) is not well known. We aimed to carry out a family study between first-degree relatives on SPLCs in Sweden.

Population data on Swedish family relationships and the diagnosed cancers were obtained from the national registers from 1961 to 2021. IPLC was diagnosed in 54,429 patients of whom 534 were diagnosed with SPLC. Familial risk was assessed through the standardized incidence ratio (SIR with 95% confidence interval) adjusted for several potential confounders, including sex, age, calendar period, educational level and geographic region. Familial risks were analyzed by type of proband, histology and sex. In addition, we estimated the effect of family history on the cumulative proportion of patients developing SPLC by sex and histology.

The estimated SIR for SPLC was 3.98 in patients without family history and 5.24 among those with a history of lung cancer in first-degree relatives. The SIR values depended on the histology of IPLC and of SPLC, with the highest SIRs for concordant histologies. For the adenocarcinoma-adenocarcinoma sequence, SIR estimates were 5.60 and 7.51 for non-familial and familial patients, respectively. The familial risks were further modulated by sex and type of affected relative, with the highest SIR for females with affected mothers (9.14).

The results showed a positive association of family history of LC with risk of SPLC on top of high risk for SPLC in non-familial patients. The risks differed by sex, histology and type of affected relative. The data on family history of LC should alert about surveillance for SPLC and may be used in future risk stratification when eligibility for population screening is considered.