The role of TP53 PRO47SER and ARG72PRO single nucleotide polymorphisms in the susceptibility to bladder cancer

Abstract

Several studies have investigated the association between TP53 Arg72Pro and an increased risk of developing bladder tumors, with controversial results. Taking advantage of the high admixture rates in the Brazilian population, we genotyped 94 bladder cancer patients (76 males and 18 females; aged 21–96 years old; 67 ± 13 years old; 79 smokers and 15 nonsmokers) carefully paired with 159 controls (104 males and 55 females; aged 20–100 years old; 65 ± 21 years old; 126 smokers and 33 nonsmokers) with respect to environmental exposure, diet routine, lifetime occupational history, smoking history, general health conditions, and previous diseases. Arg/Pro genotype was under-represented in the patient population, and conferred a 44% lower risk of bladder cancer. Univariate logistic regression analysis also identified male sex (OR = 6.87, 95% CI = 3.78–12.50; P < 0.001), age over 65 years (OR = 4.44, 95% CI = 2.56–7.71; P < 0.001), and smoking habits (OR = 18.61, 95% CI = 9.62–36.03; P < 0.001) as important risk factors for bladder cancer. However, the TP53Arg72Pro genotype disappeared as a susceptibility factor both in the multivariate regression analysis and in a univariate regression analysis adjusted for gender, age, and smoking, suggesting that it was connected with one of these factors in the predisposition to bladder cancer. Indeed, a further analysis demonstrated that both alleles and genotype variants of TP53Arg72Pro are less frequent in older patients ( P = 0.029). We concluded that the effect of TP53Arg72Pro, described in some studies as an important risk factor, may not be an independent, but an age-related factor of susceptibility to bladder cancer.