title: The TP53 Arg72Pro polymorphism and lung cancer risk in a population of Northern Spain.
abstract: Polymorphisms in tumor suppressor genes might contribute to the individual susceptibility to develop different types of cancer. Alterations in genes involved in cell cycle regulation and apoptosis, as tumor suppressor gene TP53, can lead to malignant transformations increasing the risk of developing cancer. We have investigated effects of polymorphism Arg72Pro on lung cancer risk, focusing on smoking and histology. Our study is a hospital-based case-control study designed with 589 lung cancer patients mainly with squamous cell carcinoma (215), adenocarcinoma (156) and small cell carcinoma (90), and 582 control subjects, matched in ethnicity, age and gender. Genotypes were determined by PCR-RFLP and the results were analysed using multivariate unconditional logistic regression, adjusted for age, gender and smoking status. The analysis showed a statistically significant increase of lung cancer risk in Pro carriers (Arg/Pro and Pro/Pro) (adjusted OR=1.32; 95% CI=1.03-1.69), especially for ever smokers (adjusted OR=1.34; 95% CI=1.04-1.73), heavy smokers (adjusted OR=1.48; 95% CI=1.01-2.16) and smokers of exclusively black tobacco (adjusted OR=1.45; 95% CI=1.04-2.00). Moreover, Pro carriers present an increased risk of developing small cell lung cancer (adjusted OR=1.70; 95% CI=1.07-2.69) and cancer in stage IV for NSCLC (adjusted OR=1.56; 95% CI=1.07-2.27). Our results suggest that polymorphism Arg72Pro in tumor suppressor gene TP53 increases the risk of lung cancer. The effect is especially strong for small cell lung cancer (SCLC) and heavy smokers.
authors.affiliation: Departamento de Medicina, Facultad de Medicina, Unidad de Epidemiología Molecular del Instituto Universitario de Oncología, Universidad de Oviedo, 33006 Oviedo, Spain.
authors.forename: Aida
authors.initials: A
authors.lastname: Fernández-Rubio
authors.forename: M Felicitas
authors.initials: MF
authors.lastname: López-Cima
authors.forename: Patricia
authors.initials: P
authors.lastname: González-Arriaga
authors.forename: Laura
authors.initials: L
authors.lastname: García-Castro
authors.forename: Teresa
authors.initials: T
authors.lastname: Pascual
authors.forename: Manuel G
authors.initials: MG
authors.lastname: Marrón
authors.forename: Adonina
authors.initials: A
authors.lastname: Tardón
mesh_terms: D018288:Carcinoma, Small Cell / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D016147:Genes, Tumor Suppressor; D016158:Genes, p53 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008175:Lung Neoplasms / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012306:Risk; D012907:Smoking / Q000453:epidemiology / Q000235:genetics; D013030:Spain / Q000453:epidemiology