High risk of lung cancer in surfactant-related gene variant carriers
Copyright ©The authors 2024. For reproduction rights and permissions contact permissionsersnet.org..
RATIONALE: Several rare surfactant-related genes variants associated with interstitial lung disease are suspected to be associated with lung cancer, but data are missing.
OBJECTIVES: We aimed to study the epidemiology and phenotype of lung cancer in an international cohort of surfactant-related gene (SRG) variant carriers.
METHODS: We conducted a cross-sectional study of all adults with SRG variants in the OrphaLung network and compared lung cancer risk with telomerase-related gene (TRG) variant carriers.
RESULTS: We identified 99 SRG adult variant carriers (SFTPA1 [n=18], SFTPA2 [n=31], SFTPC [n=24], ABCA3 [n=14] and NKX2-1 [n=12]), including 20 (20.2%) with lung cancer (SFTPA1 [n=7]; SFTPA2 [n=8], SFTPC [n=3], NKX2-1 [n=2] and ABCA3 [n=0]). Among SRG variant carriers, the odds of lung cancer was associated with age (odds ratio [OR] 1.04 [95% CI 1.01-1.08]), smoking (OR 20.7 [6.60-76.2]) and SFTPA1/SFTPA2 variants (OR 3.97 [1.39-13.2]). Adenocarcinoma was the only histological type reported, with PDL1 expression≥1% of tumor cells in 3 cases. Cancer staging was localized (I/II) in 8 (40%) individuals, locally advanced (III) in 2 (10%) and metastatic (IV) in 10 (50%). We found no somatic variant eligible for targeted therapy. Seven cancers were surgically removed, 10 received systemic therapy, and 3 received the best supportive care according to their stage and performance status. The median overall survival was 24 months, with stage I/II cancers showing better survival. We identified 233 TRG variant carriers. The comparative risk (subdistribution hazard ratio) for lung cancer in SRG patients versus TRG patients was 18.1 [7.1-44.7].
CONCLUSION: The high risk of lung cancer among SRG variant carriers suggests specific screening and diagnostic and therapeutic challenges. The benefit of regular CT scan follow-up should be evaluated.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
The European respiratory journal - (2024) vom: 04. Apr. |
| Sprache: |
Englisch |
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| Anmerkungen: |
Date Revised 04.04.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1183/13993003.01809-2023 |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
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| 245 | 1 | 0 | |a High risk of lung cancer in surfactant-related gene variant carriers |
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| 520 | |a Copyright ©The authors 2024. For reproduction rights and permissions contact permissionsersnet.org. | ||
| 520 | |a RATIONALE: Several rare surfactant-related genes variants associated with interstitial lung disease are suspected to be associated with lung cancer, but data are missing | ||
| 520 | |a OBJECTIVES: We aimed to study the epidemiology and phenotype of lung cancer in an international cohort of surfactant-related gene (SRG) variant carriers | ||
| 520 | |a METHODS: We conducted a cross-sectional study of all adults with SRG variants in the OrphaLung network and compared lung cancer risk with telomerase-related gene (TRG) variant carriers | ||
| 520 | |a RESULTS: We identified 99 SRG adult variant carriers (SFTPA1 [n=18], SFTPA2 [n=31], SFTPC [n=24], ABCA3 [n=14] and NKX2-1 [n=12]), including 20 (20.2%) with lung cancer (SFTPA1 [n=7]; SFTPA2 [n=8], SFTPC [n=3], NKX2-1 [n=2] and ABCA3 [n=0]). Among SRG variant carriers, the odds of lung cancer was associated with age (odds ratio [OR] 1.04 [95% CI 1.01-1.08]), smoking (OR 20.7 [6.60-76.2]) and SFTPA1/SFTPA2 variants (OR 3.97 [1.39-13.2]). Adenocarcinoma was the only histological type reported, with PDL1 expression≥1% of tumor cells in 3 cases. Cancer staging was localized (I/II) in 8 (40%) individuals, locally advanced (III) in 2 (10%) and metastatic (IV) in 10 (50%). We found no somatic variant eligible for targeted therapy. Seven cancers were surgically removed, 10 received systemic therapy, and 3 received the best supportive care according to their stage and performance status. The median overall survival was 24 months, with stage I/II cancers showing better survival. We identified 233 TRG variant carriers. The comparative risk (subdistribution hazard ratio) for lung cancer in SRG patients versus TRG patients was 18.1 [7.1-44.7] | ||
| 520 | |a CONCLUSION: The high risk of lung cancer among SRG variant carriers suggests specific screening and diagnostic and therapeutic challenges. The benefit of regular CT scan follow-up should be evaluated | ||
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