Profiling CpG island field methylation in both morphologically normal and neoplastic human colonic mucosa.

Aberrant CpG island (CGI) methylation occurs early in colorectal neoplasia. Quantitative methylation-specific PCR profiling applied to biopsies was used to quantify low levels of CGI methylation of 18 genes in the morphologically normal colonic mucosa of neoplasia-free subjects, adenomatous polyp patients, cancer patients and their tumours. Multivariate statistical analyses distinguished tumour from mucosa with a sensitivity of 78.9% and a specificity of 100% (P=3 x 10(-7)). In morphologically normal mucosa, age-dependent CGI methylation was observed for APC, AXIN2, DKK1, HPP1, N33, p16, SFRP1, SFRP2 and SFRP4 genes, and significant differences in CGI methylation levels were detected between groups. Multinomial logistic regression models based on the CGI methylation profiles from normal mucosa correctly identified 78.9% of cancer patients and 87.9% of non-cancer (neoplasia-free+polyp) patients (P=4.93 x 10(-7)) using APC, HPP1, p16, SFRP4, WIF1 and ESR1 methylation as the most informative variables. Similarly, CGI methylation of SFRP4, SFRP5 and WIF1 correctly identified 61.5% of polyp patients and 78.9% of neoplasia-free subjects (P=0.0167). The apparently normal mucosal field of patients presenting with neoplasia has evidently undergone significant epigenetic modification. Methylation of the genes selected by the models may play a role in the earliest stages of the development of colorectal neoplasia.

Tracking of 24-hour and casual blood pressure: a 1-year follow-up study in adolescents.

OBJECTIVE: Tracking of blood pressure begins in childhood but the relationship between casual blood pressure in childhood and adult levels is not strong enough to predict adult hypertension. The variability of blood pressure in children might suggest that 24 recordings would have less consistency than casual readings when repeated even a relatively short time later. This study compares the short-term tracking ability of casual versus 24-h blood pressure. DESIGN: An ambulatory blood pressure device was placed on 50 teenagers. Readings were taken at rest and the device was then worn for approximately 24 h, which included the schoolday. The protocol was repeated 1 year later. RESULTS: The correlation coefficient for systolic readings taken 1 year later were: 0.4 for casual, 0.6 for school, 0.6 for home, 0.5 for night-time and 0.8 for 24-h mean systolic blood pressures. When divided into upper and lower tertiles of systolic blood pressure the relationship between tertile ranking 1 year later was stronger for 24-h blood pressure than the casual readings. Casual diastolic pressure was more consistent than the 24-h mean diastolic measurement. CONCLUSIONS: In adolescents, in whom tracking of casual blood pressure has been shown to be poor, 24-h mean systolic blood pressure tracks better than any other time period and significantly better than the casual systolic readings. This study needs to be extended and the ability of 24-h blood pressure to track from childhood to adult life investigated.