BackgroundSomatic genetic CDKN2A, TP53, and DNA content abnormalities are common in many human cancers and their precursors, including esophageal adenocarcinoma (EA) and Barrett's esophagus (BE), conditions for which aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) have been proposed as possible chemopreventive agents; however, little is known about the ability of a biomarker panel to predict progression to cancer nor how NSAID use may modulate progression. We aimed to evaluate somatic genetic abnormalities with NSAIDs as predictors of EA in a prospective cohort study of patients with BE.Methods and FindingsEsophageal biopsies from 243 patients with BE were evaluated at baseline for TP53 and CDKN2A (p16) alterations, tetraploidy, and aneuploidy using sequencing; loss of heterozygosity (LOH); methylation-specific PCR; and flow cytometry. At 10 y, all abnormalities, except CDKN2A mutation and methylation, contributed to EA risk significantly by univariate analysis, ranging from 17p LOH (relative risk [RR] = 10.6; 95% confidence interval [CI] 5.2–21.3, p < 0.001) to 9p LOH (RR = 2.6; 95% CI 1.1–6.0, p = 0.03). A panel of abnormalities including 17p LOH, DNA content tetraploidy and aneuploidy, and 9p LOH was the best predictor of EA (RR = 38.7; 95% CI 10.8–138.5, p < 0.001). Patients with no baseline abnormality had a 12% 10-y cumulative EA incidence, whereas patients with 17p LOH, DNA content abnormalities, and 9p LOH had at least a 79.1% 10-y EA incidence. In patients with zero, one, two, or three baseline panel abnormalities, there was a significant trend toward EA risk reduction among NSAID users compared to nonusers (p = 0.01). The strongest protective effect was seen in participants with multiple genetic abnormalities, with NSAID nonusers having an observed 10-y EA risk of 79%, compared to 30% for NSAID users (p < 0.001).ConclusionsA combination of 17p LOH, 9p LOH, and DNA content abnormalities provided better EA risk prediction than any single TP53, CDKN2A, or DNA content lesion alone. NSAIDs are associated with reduced EA risk, especially in patients with multiple high-risk molecular abnormalities.

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Purpose: Leukocyte telomere length has gained attention as a marker of oxidative damage and age-related diseases, including cancer. We hypothesize that leukocyte telomere length might be able to predict future risk of cancer and examined this in a cohort of patients with Barrett's esophagus, who are at increased risk of esophageal adenocarcinoma and thus were enrolled in a long-term cancer surveillance program. Patients and Methods: In this prospective study, telomere length was measured by quantitative PCR in baseline blood samples in a cohort of 300 patients with Barrett's esophagus followed for a mean of 5.8 years. Leukocyte telomere length hazard ratios (HR) for risk of esophageal adenocarcinoma were calculated using multivariate Cox models. Results: Shorter telomeres were associated with increased esophageal adenocarcinoma risk (age-adjusted HR between top and bottom quartiles of telomere length, 3.45; 95% confidence interval, 1.35-8.78; P = 0.009). This association was still significant when individually or simultaneously adjusted for age, gender, nonsteroidal anti-inflammatory drug (NSAID) use, cigarette smoking, and waist-to-hip ratio (HR, 4.18; 95% confidence interval, 1.60-10.94; P = 0.004). The relationship between telomere length and cancer risk was particularly strong among NSAID nonusers, ever smokers, and patients with low waist-to-hip ratio. Conclusion: Leukocyte telomere length predicts risk of esophageal adenocarcinoma in patients with Barrett's esophagus independently of smoking, obesity, and NSAID use. These results show the ability of leukocyte telomere length to predict the risk of future cancer and suggest that it might also have predictive value in other cancers arising in a setting of chronic inflammation. (Cancer Epidemiol Biomarkers Prev 2007;16(12):2649-55)

Exercise effect on weight and body fat in men and women. Obesity. 2007;15: 1496 -1512. Objectives: The effect of national exercise recommendations on adiposity is unknown and may differ by sex. We examined long-term effects of aerobic exercise on adiposity in women and men. Research Methods and Procedures: This was a 12-month randomized, controlled clinical trial testing exercise effect on weight and body composition in men (N ϭ 102) and women (N ϭ 100). Sedentary/unfit persons, 40 to 75 years old, were recruited through physician practices and media. The intervention was facility-and home-based moderate-tovigorous intensity aerobic activity, 60 min/d, 6 days/wk vs. controls (no intervention). Results: Exercisers exercised a mean 370 min/wk (men) and 295 min/wk (women), and seven dropped the intervention. Exercisers lost weight (women, Ϫ1.4 vs. ϩ0.7 kg in controls, p ϭ 0.008; men, Ϫ1.8 vs. Ϫ0.1 kg in controls, p ϭ 0.03), BMI (women, Ϫ0.6 vs. ϩ0.3 kg/m 2 in controls, p ϭ 0.006; men, Ϫ0.5 kg/m 2 vs. no change in controls, p ϭ 0.03), waist circumference (women, Ϫ1.4 vs. ϩ2.2 cm in controls, p Ͻ 0.001; men, Ϫ3.3 vs. Ϫ0.4 cm in controls, p ϭ 0.003), and total fat mass (women, Ϫ1.9 vs. ϩ0.2 kg in controls, p ϭ 0.001; men, Ϫ3.0 vs. ϩ0.2 kg in controls, p Ͻ 0.001). Exercisers with greater increases in pedometer-measured steps per day had greater decreases in weight, BMI, body fat, and intra-abdominal fat (all p trend Ͻ 0.05 in both men and women). Similar trends were observed for increased minutes per day of exercise and for increases in maximal oxygen consumption. Discussion: These data support the U.S. Department of Agriculture and Institute of Medicine guidelines of 60 min/d of moderate-to-vigorous physical activity.

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Compared to Westerners, Chinese patients have a slightly lower prevalence of colon neoplasia (but not advanced neoplasia), more distal distribution of neoplasia, and higher likelihood of concomitant proximal advanced neoplasia and distal neoplasia. Colonoscopy is safe, well-tolerated, and a viable screening option in Chinese patients, but its advantage over sigmoidoscopy as a screening tool may be smaller.

The extent of LGD is a significant risk factor for the development of EA in BE in this study. Although the presence of HGD is significantly associated with a greater relative risk for development of EA, the extent of HGD was not an independent risk factor for progression.