The p53 R72P polymorphism does not influence cervical cancer development in a Portuguese population: a study in exfoliated cervical cells.

The interaction between the E6 protein of the high-risk human papillomaviruses (HPVs) with p53 seems to be crucial in cervical carcinogenesis. The presence of Arg/Arg genotype at codon 72 of TP53 gene was characterized as a risk factor in development of cervical cancer. However, the role of this polymorphism remains controversial and some authors suggested that the origin of DNA (blood or exfoliated cervical cells) might influence these results. This study analyzed the effect of the p53 codon 72 polymorphism (R72P) in exfoliated cervical cells of women from the northern region of Portugal using two methodologies: allele-specific polymerase chain reaction and real-time polymerase chain reaction. We studied 700 cervical exfoliated cells which showed: 334 cases from women without cervical cancer or cervical lesion (N), 114 low-grade squamous intraepithelial lesions (LSIL), 107 high-grade squamous intraepithelial lesions (HSIL), 20 invasive cervical cancers (ICC) and 125 atypical squamous cells of unknown significance (ASCUS). No statistically significant differences between cases and controls were found, regarding the influence of the R72P polymorphism with cytological classification, high risk-HPV infection and HPV16 presence (P = 0.336, P = 0.945, and P = 0.964, respectively). Also, the influence of this polymorphism in the median age of onset for LSIL, HSIL, and ICC was not statistically significant (P = 0.674, P = 0.810, and P = 0.928, respectively). Therefore, the hypothesis that women with Arg/Arg genotype have an increased risk of developing cervical cancer failed to be proven in this study. Moreover, our study reveals that results using exfoliated cervical cells are reliable as compared with studies on blood.

Long-term gallbladder stone recurrence and risk factors after successful lithotripsy.

OBJECTIVE: The risk of recurrence has limited the acceptability of conservative therapies of gallbladder stones. The aim of the present study was to determine the rate of stone recurrence and its risk factors, after successful shock-wave lithotripsy. DESIGN: Prospective ultrasound follow-up at yearly intervals or whenever biliary pain was reported. METHODS: One hundred and fifty-eight consecutive patients (single stone, n = 130; two or three stones, n = 28) were followed up to 70 months (median, 33 months) after stone disappearance and discontinuation of ursodeoxycholic acid. RESULTS: Forty-three patients developed recurrent stones. By actuarial analysis, the recurrence rates (as a percent) at 1, 2, 3, 4 and 5 years were, respectively: 6+/-2, 14+/-3, 27+/-4, 35+/-5, and 44+/-6 (observed +/- SE). Cox's regression analysis identified high body mass indexes to be a risk factor (P = 0.02) for newly formed stones. Having had a single primary stone did not seem to be protective. Fourteen of the 43 patients (33%) had early symptoms of recurrence. Thirty-eight patients (89%) chose to undergo oral dissolution again, which was complemented by lithotripsy in eight patients (19%). CONCLUSION: The 5-year gallbladder stone recurrence after lithotripsy and ursodeoxycholic acid is not substantially smaller than that reported by post-bile acid studies. Obesity is a risk factor for recurrent stones as it is for primary stones. Most patients with secondary stones choose to have conservative therapy again. Gallbladder stone recurrence still is one of the major drawbacks of these treatments and cost-effective strategies are needed to prevent it.