14P MMP-2 1306 C/T promoter polymorphism and smoking: A possible role as risk factors in lung cancer

Abstract

Background: Lung cancer is the leading cause of cancer death in both gender accounting for 15% of deaths among young people (0–49 years), 30% among adults (50–69 years) and 27% among those over seventy. Matrix metalloproteases (MMPs) are a large family of proteins consisting of at least 26 human MMPs. They are zincdependent endopeptidases that cleave components of the extracellular matrix (ECM) and basement membrane and has been reported that play an important role in several steps of cancer development. Many studies have shown that a nucleotide polymorphism (–1306C3T) in the MMP2 promoter in addition to smoking and age are major risk factors for the onset of lung cancer. The aim of this study was to examine the association of MMP-2 polymorphism and smoke as a risk for cancer in 71 Italians lung cancer patients. Methods: Seventy-one patients (56 men and 15 women) aged between 44 and 84 years with adeno or squamous carcinoma in inoperable stage IIIA/IIIB/IV were enrolled in this study; information about clinical and histopathological data and smoking habits were collected through the clinical charts; genotyping was performed using direct DNA sequencing. Results: 44/71 patients (62%) had the CC genotype, 15/71 (21%) patients had CT genotype and 12/71 (16%) had TT genotype. About smoking 47/71 (66%) patients were smokers, 5/71 (7%) patients had never smoked and 19/71 (26%) of them were ex-smokers and had stopped for at least 3 years. In subgroup of smokers patients, the overall average number of years of smoke was 44, the average number of smoked cigarettes was 25 and the number of pack-year 48; the smoker group was divided into heavy smokers smoking from 50 to 60 cigarettes/day, a group of heavy smokers smoking from 11 to 49 cigarettes/day and light smokers smoking from 2 to 10 cigarettes/day. A higher allelic frequency of CC genotype and stage IV disease in the heavy and mean smoking group were observed compared to light smokers (p < 0.001 and p < 0.0001 respectively) while the TT genotype was much more frequent in stage III and in subgroup of light smokers (p < 0.05). Conclusions: These preliminary results suggest a significant association between the mmp2-1306c/t polymorphism and smoke that could represent a significant risk factors of developing lung cancer. Legal entity responsible for the study: IRCCS Istituto Tumori Giovanni Paolo II Funding: Has not received any funding Disclosure: All authors have declared no conflicts of interest.