ASSOCIATION BETWEEN THE CYP1A1 GENE POLYMORPHISM AND SUSCEPTIBILITY TO EMPHYSEMA AND LUNG-CANCER

Aim-To investigate cytochrome P4501A1 (CYP1A1) polymorphism and suscep tibility to emphysema and lung cancer. Methods-A novel polymerase chai n reaction (PCR) for genotyping the CYP1A1 polymorphism, corresponding to putative low or high enzyme activity, was developed to genotype lu ng cancer resection samples which had been assessed macroscopically fo r the presence of centriacinar and panacinar emphysema. Samples were c ollected and genotyped from a group of patients with chronic obstructi ve airways disease. A control group of anonymous blood donations was g enotyped to determine the basal levels of the polymorphism in the Scot tish population. Results-The high activity allele of the CYP1A1 gene i s associated with susceptibility to centriacinar emphysema and lung ca ncer but not panacinar emphysema. CYP1A1 polymorphism is not linked to lung cancer in the absence of emphysema, nor to chronic obstructive a irways disease which is the clinical manifestation of emphysema, parti cularly of the panacinar type. Conclusions-Susceptibility to emphysema and lung cancer is associated with polymorphism of the P4501A1 gene. A trend towards damage of centriacinar pattern has been detected, whic h supports the theory that centriacinar emphysema results from local, direct damage to the respiratory bronchioles from exposure to cigarett e smoke.