Central adiposity, obesity during early adulthood, and pancreatic cancer mortality in a pooled analysis of cohort studies.

BACKGROUND: Body mass index (BMI), a measure of obesity typically assessed in middle age or later, is known to be positively associated with pancreatic cancer. However, little evidence exists regarding the influence of central adiposity, a high BMI during early adulthood, and weight gain after early adulthood on pancreatic cancer risk. DESIGN: We conducted a pooled analysis of individual-level data from 20 prospective cohort studies in the National Cancer Institute BMI and Mortality Cohort Consortium to examine the association of pancreatic cancer mortality with measures of central adiposity (e.g. waist circumference; n = 647 478; 1947 pancreatic cancer deaths), BMI during early adulthood (ages 18-21 years) and BMI change between early adulthood and cohort enrollment, mostly in middle age or later (n = 1 096 492; 3223 pancreatic cancer deaths). Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models. RESULTS: Higher waist-to-hip ratio (HR = 1.09, 95% CI 1.02-1.17 per 0.1 increment) and waist circumference (HR = 1.07, 95% CI 1.00-1.14 per 10 cm) were associated with increased risk of pancreatic cancer mortality, even when adjusted for BMI at baseline. BMI during early adulthood was associated with increased pancreatic cancer mortality (HR = 1.18, 95% CI 1.11-1.25 per 5 kg/m(2)), with increased risk observed in both overweight and obese individuals (compared with BMI of 21.0 to <23 kg/m(2), HR = 1.36, 95% CI 1.20-1.55 for BMI 25.0 < 27.5 kg/m(2), HR = 1.48, 95% CI 1.20-1.84 for BMI 27.5 to <30 kg/m(2), HR = 1.43, 95% CI 1.11-1.85 for BMI ≥30 kg/m(2)). BMI gain after early adulthood, adjusted for early adult BMI, was less strongly associated with pancreatic cancer mortality (HR = 1.05, 95% CI 1.01-1.10 per 5 kg/m(2)). CONCLUSIONS: Our results support an association between pancreatic cancer mortality and central obesity, independent of BMI, and also suggest that being overweight or obese during early adulthood may be important in influencing pancreatic cancer mortality risk later in life.

Autoantibodies to the nuclear phosphoprotein nucleophosmin in breast cancer patients.

Nucleophosmin (NPM) is an estrogen-regulated nucleolar phosphoprotein; a substrate for phosphorylation by p34cdc2 kinase, protein kinase C, and casein kinase II; and a repressor of the transcriptional regulating activities of the YY1 and IFN regulatory factor-1 transcription factors. We have completed a pilot study to determine whether autoantibodies to NPM are present in breast cancer patients and explored the ability of these autoantibodies to predict recurrence in breast cancer patients. One hundred breast cancer patients were studied: 50 who recurred, and 50 matched for age and length of follow-up but who did not recur. Patients' sera were collected at the times of diagnosis (T1), six months before recurrence (T2), and at recurrence (T3). Recurrent and nonrecurrent patients did not differ in autoantibody levels at the times of diagnosis or recurrence. However, antiNPM autoantibody levels increase significantly between diagnosis and six months before recurrence in recurrent patients, whereas no change occurs over the comparable time period in nonrecurrent patients (repeated measures ANOVA; P = 0.041). At recurrence, the levels return to those seen at diagnosis. The greater the change in levels between T1 and T2, the greater the risk of recurrence within the next 6 months (conditional logistic regression: increase in risk for highest versus lowest tertile of change from T1 to T2; odds ratio, 3.25; 95% confidence interval, 1.04-10.18; P = 0.043). Consistent with the estrogenic/antiestrogenic regulation of the antigen in breast cancer cells, the levels of antiNPM autoantibodies are decreased 6 months before recurrence in patients treated with the antiestrogen tamoxifen (P = 0.012). The association between antiNPM levels and recurrence remained after adjustment for confounding factors. Further study of antiNPM autoantibody levels as a new and simple, intermediate serum biomarker for predicting both the timing of recurrence and monitoring response to endocrine manipulations in breast cancer patients is warranted.