Fred Tabung

PhD, MSPH

The Ohio State University

Assistant Professor

PLCO (Learn more about this study)

PLCO-780

May 7, 2021

Associations of inflammatory and insulinemic dietary patterns and risk of colorectal adenomas in men and women: Findings from the PLCO cohort

Background: Colorectal cancer (CRC) is the third most commonly diagnosed malignancy and the second leading cause of cancer deaths in the U.S. Modifiable exposures like diet may play a major role in colorectal cancer etiology, but underlying mechanisms are not well understood. We previously developed the empirical dietary inflammatory pattern (EDIP) score that represents the pattern of foods consumed as part of a whole diet that affects circulating inflammatory biomarkers including C-reactive protein, interleukin-6 and TNF-R2. We also developed the hypothesis-oriented empirical dietary index for hyperinsulinemia (EDIH) score that represents the pattern of foods consumed as part of a whole diet that affects circulating C-peptide, a marker of insulin resistance and β-cell secretory activity. Higher EDIP and EDIH scores link to higher inflammatory or insulinemic potential of the diet, respectively. While these novel dietary patterns have been strongly associated with CRC risk, including young-onset CRC, whether they influence earlier stages of colorectal carcinogenesis is not known.

Objective: to calculate the EDIP and EDIH scores at baseline and assess their associations with risk of incident adenoma, advanced adenoma and recurrent adenoma. We will also assess the associations of EDIH and EDIP with concentrations of IGF system biomarkers.

Study participants: 77,445 men and women were randomized to the trial arm of PLCO, and 79% completed a study questionnaire and food frequency questionnaire at baseline. At the 3rd and 5th year of follow-up (T3/T5), 26,766 participants aged 55-74 years who had no history of colorectal cancer, completed sigmoidoscopy examinations. Incident colorectal adenoma cases were defined as individuals with a positive follow-up sigmoidoscopy, which was subsequently confirmed during diagnostic endoscopy. This sample will also be free from history of colorectal polyps, Crohn’s disease, ulcerative colitis, familial polyposis, or Gardner’s syndrome at baseline. The analytic sample for the incident adenoma analysis will comprise about 21,000 participants, including ~51% men and ~1,200 incident adenoma cases. We will also examine the risk of advanced adenoma (n~260 cases), defined as large polyps (≥1cm), had high-grade dysplasia (including carcinoma in situ), or had villous elements (including tubulo-villous adenomas). For recurrent adenoma analysis, we will include participants who were diagnosed with adenoma at baseline endoscopy (verified by medical record abstraction), received a subsequent endoscopy between 6 months and 10 years after baseline endoscopy (surveillance endoscopy), and completed baseline questionnaires. After exclusions similar to the incident adenoma analysis, we expect to retain about 1700 participants including ~63% men and 750 recurrent adenoma cases. There are ~8,743 participants with IGF system biomarkers.

Analysis: We will use multivariable-adjusted Cox proportional hazards regression to examine associations between the two dietary scores and risk of incident adenoma, advanced incident adenoma, and recurrent adenoma. For the biomarkers, we will conduct multivariable-adjusted linear regression to determine associations between EDIH and EDIP with concentrations of IGF system biomarkers, including IGF-1, IGF-2, IGF binding protein (BP)-1, IGFBP-2 and IGFBP-3. All analyses will be adjusted for the following potential confounding variables: age, sex, smoking status, total alcohol intake, marital status, educational level, physical activity, body mass index and NSAID use.

Our objective is to calculate the EDIP and EDIH scores at PLCO baseline and assess their associations with risk of colorectal adenomas, based on the hypothesis that higher intake of proinflammatory and hyperinsulinemic dietary patterns (higher EDIP and EDIH scores, respectively) is associated with higher risk of both incident adenomas and recurrent adenomas.

We will conduct multivariable-adjusted linear regression models to determine associations between EDIH and EDIP with concentrations of IGF system biomarkers, adjusting for the aforementioned covariates. IGF outcome markers will include IGF-1, IGF-2, IGF binding protein (BP)-1, IGFBP-2 and IGFBP-3.