Association of p21 Ser31Arg and p53 Arg72Pro polymorphisms with lung cancer risk in CAPUA study

Abstract

Ana Souto-García,1,2 Ana Fernández-Somoano,1,2 Teresa Pascual,3 Sara M Álvarez-Avellón,1,2 Adonina Tardón1,21Molecular Epidemiolgy of Cancer Unit, University Institute of Oncology, University of Oviedo, Oviedo, Asturias, Spain; 2Consortium for Research in Epidemiology and Public Health (CIBERESP), Spain; 3Pneumology Department, Cabueñes Hospital, Gijón, Asturias, SpainBackground: The aim of this study was to investigate how Ser31Arg polymorphisms in p21 may modify lung cancer susceptibility. Because p21 is the major downstream mediator of p53, we analyzed the combined effect of two polymorphisms, p21 Ser31Arg and TP53 Arg72Pro, to elucidate whether polymorphic variants determine the risk of lung cancer.Methods: This was designed as a hospital-based case-control study, and included 675 cases and 675 control subjects matched by ethnicity, gender, and age. Genotypes were determined by polymerase chain reaction restriction fragment length polymorphism, and multivariate unconditional logistic regression was performed to analyze the results.Results: Subjects who carried the p21 Ser31Arg allele had a higher risk of lung cancer (adjusted odds ratio [OR] 1.38; 95% confidence interval [CI] 0.99–2.03). This risk was increased in men aged younger than 55 years (adjusted OR 2.35; 95% CI 1.00–5.51). Smokers had an increased risk of lung cancer (adjusted OR 2.23; 95% CI 1.24–4.02). Men younger than 55 years carrying risk alleles for both genes (p21 Ser31Arg and TP53 Arg72Pro) had an increased risk (adjusted OR 5.78; 95% CI 1.38–24.19), as did smokers with both risk alleles (adjusted OR 4.52; 95% CI 1.52–13.50).Conclusion: The presence of both variant alleles increased the risk of developing lung cancer in men, particularly in smokers younger than 55 years.Keywords: molecular epidemiology, cell cycle, tobacco, susceptibility, oncology