High Prevalence and impact of lung cancer in Surfactant related gene mutation carriers

Abstract

The prevalence of lung cancer is high in patients with interstitial lung disease (ILD). Several germline mutations are associated with ILD, mutations of surfactant related genes (SRG: SFTPA1, A2, B and C, ABCA3 and NKX2.1) are second in frequency but seem associated with a higher prevalence of lung cancer. We conducted a cohort study in the OrphaLung network of all adult patients diagnosed with SRG mutations to determine the penetrance and phenotype of lung cancer in this population. We retrieved 76 adults (SFTPA2 n=29; SFTPA1 n=18; NKX2.1 n=12; SFTPC n=11, ABCA3 n=6) including 17 lung cancer (SFTPA1 n=7; SFTPA2 n=6; SFTPC n=3; NKX2.1 n=1, ABCA3 n=0). Median age at lung cancer diagnosis was 50 years-old vs 46.5 at last follow-up visit in non-cancer patients (p=0.04). Sex-ratio was not different (1.1 vs 0.9, OR 1.2, [0.3-4], p=0.8). Smoking was more frequent in the cancer group (88% vs 19%, OR 30, [5-312], p<0.001). Adenocarcinoma (invasive mucinous 40%, acinar 40%, lepidic 20%) was the only histological type, with PDL1 expression <1% in all cases. Four tumors showed K-RAS mutation without any other driver somatic mutation/translocation described in lung cancer. Staging showed localized cancer (I-II) for 7 patients (35%), locally advanced (III) for 1 (12%) and metastatic cancer (IV) for 9 (53%). Five cancers were surgically removed, 9 got systemic treatment (including 1 adjuvant) and 3 got best standard of care. The median OS was 16 months (stage I-II: 60 months; stage III : 24 months; stage IV : 14 months). Lung cancer prevalence was 22% in this adult patients with SRG mutations, and increased by age and smoking. Adenocarcinoma was more frequent compared to other cohorts of cancer and ILD.