Alpha-1 Antitrypsin Deficiency and Lung Cancer Risk: A Case-Control Study in Never-Smokers.
BACKGROUND
Never-smokers comprise up to 25% of all lung cancer cases. They could have different molecular pathways for lung cancer induction compared with smokers. Alpha-1 antitrypsin (AAT) deficiency is a hereditary trait whose main characteristic is early onset of lung emphysema. Our aim is to know if AAT-deficient carriers have a higher risk of lung cancer in a study performed exclusively in never-smokers.


METHODS
We designed a multicentre hospital-based case-control study, which included incident never-smoking lung cancer cases. Controls were never-smokers attending nonmajor surgery at the participating hospitals. Controls were frequency matched on age and gender with cases. We determined AAT variants (alleles S and Z) through polymerase chain reaction.


RESULTS
Two hundred and twelve cases and 318 controls were included. PiSS individuals showed a lung cancer risk of 4.64 (95% confidence interval: 1.08-19.92) compared with those with normal genotype (PiMM). When the analysis was restricted to women, the risk for PiSS increased to 7.58 (95% confidence interval: 1.40-40.87). This risk for homozygous SS was even higher for individuals exposed to environmental tobacco smoke (greater than 20 years). The presence of other alleles did not show any effect on lung cancer risk.


CONCLUSIONS
Never smoking SS homozygous individuals pose an increased risk of lung cancer. The risk is higher for individuals exposed to environmental tobacco smoke.
Service of Pneumology, University Hospital Complex of Vigo, Vigo, Spain.
María
M
Torres-Durán
Department of Preventive Medicine and Public Health, University of Santiago de Compostela, Santiago de Compostela, Spain; CIBER de Epidemiología y Salud Pública, CIBERESP Madrid, Spain. Electronic address: alberto.ruano@usc.es.
Alberto
A
Ruano-Ravina
Service of Pneumology, Ourense Hospital Complex, Ourense, Spain.
Isaura
I
Parente-Lamelas
Service of Pneumology, Ourense Hospital Complex, Ourense, Spain.
José
J
Abal-Arca
Service of Pneumology, University Hospital Complex of Vigo, Vigo, Spain.
Virginia
V
Leiro-Fernández
Service of Pneumology, University Hospital Complex of A Coruña, A Coruña, Spain.
Carmen
C
Montero-Martínez
Service of Oncology, Pontevedra Hospital Complex, Pontevedra, Spain.
Carolina
C
Pena
Service of Pneumology, Hospital Lucus Augusta, Lugo, Spain.
Olalla
O
Castro-Añón
Service of Pneumology, Santiago de Compostela University Clinic Hospital, Santiago de Compostela, Spain.
Antonio
A
Golpe-Gómez
Service of Pneumology, Santiago de Compostela University Clinic Hospital, Santiago de Compostela, Spain; CIBER de Enfermedades Respiratorias, CIBERES, Madrid, Spain.
Francisco J
FJ
González-Barcala
National Institute of Silicosis, University Hospital of Asturias, Oviedo, Spain.
Cristina
C
Martínez
National Institute of Silicosis, University Hospital of Asturias, Oviedo, Spain.
Rosirys
R
Guzmán-Taveras
Service of Oncology, Puerta de Hierro University Hospital, Madrid, Spain.
Mariano
M
Provencio
Service of Pneumology, Arquitecto Marcide Hospital, Ferrol, Spain.
María José
MJ
Mejuto-Martí
Service of Pneumology, University Hospital Complex of Vigo, Vigo, Spain.
Alberto
A
Fernández-Villar
Department of Preventive Medicine and Public Health, University of Santiago de Compostela, Santiago de Compostela, Spain; CIBER de Epidemiología y Salud Pública, CIBERESP Madrid, Spain; Service of Preventive Medicine, University Hospital Complex of Santiago de Compostela, Santiago de Compostela, Spain.
Juan Miguel
JM
Barros-Dios
D000368:Aged; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D019896:alpha 1-Antitrypsin Deficiency / Q000150:complications*