Fibre-rich Foods to Treat Obesity and Prevent Colon Cancer trial study protocol: a randomised clinical trial of fibre-rich legumes targeting the gut microbiome, metabolome and gut transit time of overweight and obese patients with a history of noncancerous adenomatous polyps.

INTRODUCTION: Recently published studies support the beneficial effects of consuming fibre-rich legumes, such as cooked dry beans, to improve metabolic health and reduce cancer risk. In participants with overweight/obesity and a history of colorectal polyps, the Fibre-rich Foods to Treat Obesity and Prevent Colon Cancer randomised clinical trial will test whether a high-fibre diet featuring legumes will simultaneously facilitate weight reduction and suppress colonic mucosal biomarkers of colorectal cancer (CRC). METHODS/DESIGN: This study is designed to characterise changes in (1) body weight; (2) biomarkers of insulin resistance and systemic inflammation; (3) compositional and functional profiles of the faecal microbiome and metabolome; (4) mucosal biomarkers of CRC risk and (5) gut transit. Approximately 60 overweight or obese adults with a history of noncancerous adenomatous polyps within the previous 3 years will be recruited and randomised to one of two weight-loss diets. Following a 1-week run-in, participants in the intervention arm will receive preportioned high-fibre legume-rich entrées for two meals/day in months 1-3 and one meal/day in months 4-6. In the control arm, entrées will replace legumes with lean protein sources (eg, chicken). Both groups will receive in-person and written guidance to include nutritionally balanced sides with energy intake to lose 1-2 pounds per week. ETHICS AND DISSEMINATION: The National Institutes of Health fund this ongoing 5-year study through a National Cancer Institute grant (5R01CA245063) awarded to Emory University with a subaward to the University of Pittsburgh. The study protocol was approved by the Emory Institutional Review Board (IRB approval number: 00000563). TRIAL REGISTRATION NUMBER: NCT04780477.

Oxidative balance score and risk for incident prostate cancer in a prospective U.S. cohort study.

PURPOSE: Oxidative stress is defined as an imbalance between pro-oxidants and antioxidants. Previous research found that a single comprehensive oxidative balance score (OBS) that includes individual pro- and anti-oxidant exposures may be associated with various conditions (including prostate cancer) in the absence of associations with the individual factors. We investigated an OBS-incident prostate cancer association among 43,325 men in the Cancer Prevention Study II Nutrition Cohort. METHODS: From 1999-2007, 3386 incident cases were identified. Twenty different components, used in two ways (unweighted or weighted based on literature reviews), were incorporated into the OBS, and the resulting scores were then expressed as three types of variables (continuous, quartiles, or six equal intervals). Multivariable-adjusted rate ratios were calculated using Cox proportional hazards models. RESULTS: We hypothesized that the OBS would be inversely associated with prostate cancer risk; however, the rate ratios (95% confidence intervals) comparing the highest with the lowest OBS categories ranged from 1.17 (1.04-1.32) to 1.39 (0.90-2.15) for all cases, 1.14 (0.87-1.50) to 1.59 (0.57-4.40) for aggressive disease (American Joint Committee on Cancer stage III/IV or Gleason score 8-10), and 0.91 (0.62-1.35) to 1.02 (1.02-1.04) for nonaggressive disease. CONCLUSIONS: Our findings are not consistent with the hypothesis that oxidative balance-related exposures collectively affect risk for prostate cancer.

First-trimester maternal plasma cytokine levels, pre-pregnancy body mass index, and spontaneous preterm delivery.

OBJECTIVE: To examine associations between first-trimester plasma cytokines and spontaneous preterm delivery (sPTD). DESIGN: A case-control study was nested within the Danish National Birth Cohort, a cohort of women with 101,042 pregnancies from 1997 to 2002 who were recruited during pregnancy and followed prospectively. SAMPLE: Subjects included 107 women delivering singleton infants at 24-29 weeks, 353 at 30-33 weeks, 422 at 34-36 weeks, and 1,372 at > or =37 weeks. METHODS: Maternal plasma interleukin (IL)-2, IL-6, tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, and granulocyte-macrophage colony-stimulating factor (GM-CSF) were measured at a median of eight weeks gestation using multiplex flow cytometry. Adjusted odds ratios (ORs) were obtained using polytomous logistic regression. MAIN OUTCOME MEASURES: sPTD categorized as: 24-29 weeks, 30-33 weeks, 34-36 weeks, and > or =37 weeks (controls). RESULTS: Elevated TNF-alpha and GM-CSF were associated with an increased risk of delivery at 34-36 weeks. In underweight women, sPTD <34 weeks was associated with elevated (>75th percentile) IL-6 (OR=5.62, 95% confidence interval (CI): 1.73, 18.26) and TNF-alpha (OR=3.02, CI: 1.02, 8.91) compared with term delivery. Conversely, among obese women, elevated IL-2 (OR=0.30, CI: 0.11, 0.78) and TNF-alpha (OR=0.15, CI: 0.05, 0.47) were associated with a reduced risk of delivering at <34 weeks. Cytokines were not related to delivery at <34 weeks in normal-weight and overweight women. CONCLUSIONS: These findings suggest that the association between first-trimester plasma cytokine levels and sPTD may depend on pre-pregnancy body mass index.

TGF-alpha expression as a potential biomarker of risk within the normal-appearing colorectal mucosa of patients with and without incident sporadic adenoma.

BACKGROUND: Transforming growth factor-alpha (TGF-alpha), a stimulatory growth factor and member of the epidermal growth factor family, is a mediator of oncogenesis and malignant progression in colorectal carcinogenesis. Limited evidence suggests its utility as a growth-related biomarker of risk for colorectal cancer. METHODS: We measured expression of TGF-alpha in biopsies of normal-appearing colorectal mucosa using automated immunohistochemistry and quantitative image analysis in a subsample of 29 cases and 31 controls from a colonoscopy-based case-control study (n = 203) of biomarkers of risk for incident sporadic colorectal adenoma. Diet, lifestyle, and medical history were assessed with validated questionnaires. RESULTS: TGF-alpha expression in the rectum was 51% higher in cases compared with controls (P = 0.05) and statistically significantly associated with accepted risk factors for colorectal neoplasms (36% lower among nonsteroidal anti-inflammatory drug users, 49% lower among women using hormone replacement therapy, 79% higher among persons with a family history of colorectal cancer). CONCLUSIONS: TGF-alpha expression in the normal-appearing rectal mucosa shows promise as an early, potentially modifiable biomarker of risk for colorectal cancer.