Screening and Risk Factors of Colon Neoplasia

For this aim, we will recruit a sub-sample of the study participants to perform the sDNA test for aberrantly methylated markers in addition to their colonoscopy to assess willingness to participate, compliance with test protocol and patient satisfaction to determine potential for a larger study to evaluate the effectiveness of this test for detection of colon adenomas.

For the sDNA test aims, the primary goals are to assess the sensitivity and specificity of sDNA testing for the detection of advanced adenomas, and to compare the performance of the Exact sDNA Panel with that of FIT. The sensitivity and specificity of sDNA and FIT will be estimated based on the concordance and discordance of advanced adenomas detected against that of colonoscopy as the gold standard

Biopsies of rectal and colon mucosa collected at the beginning of the colonoscopy for analysis of 15-PGDH pathway factors [levels of prostaglandin E2 (PG E2), and mRNA for 15-PGDH, COX-1 and COX-2 expression] as markers of risk of developing adenoma.

For this aim we will follow-up participants who have had positive sDNA tests and at least one advanced adenoma removed during colonoscopy. At 12 months after their initial sDNA test and colonoscopy, we will ask them to repeat the sDNA test in addition to colonoscopy recommended by their physician as standard of care.

For this aim we will follow-up participants who have had positive sDNA tests and negative colonoscopy (i.e., no adenomatous polyps observed at initial colonoscopy). At 12 months after their initial sDNA test and colonoscopy, we will ask them to repeat the sDNA test. If this second sDNA test is also positive, the participant will be offered the opportunity to have both a colonoscopy and an upper GI endoscopy (also called esophagogastroduodenoscopy or EGD)

Use latent structural equation models to fully incorporate information on the overall relations among insulin resistance syndrome pathway factors and colon polyps, including both direct and indirect effects as well as interactions between these factors.

The analysis by ethnicity is of particular interest in sDNA testing as there is evidence that large right-sided adenomas are more prevalent among African Americans, and this ethnic population is less likely to receive screening colonoscopy as compared to Caucasians. Furthermore, the ability of sDNA and FIT for the detection of nonadvanced adenomas will be evaluated. These lesions will be defined as adenomas that are less than 1 cm in diameter and without evidence of high grade dysplasia.

Evaluate whether each of the following candidate gene polymorphisms and their haplotypes are linked to colon polyps: 1) Insulin; 2) Growth Hormone; 3) IGF-1; and 4) IRS-1.

Conceptually, dietary patterns represent a broader picture of human diet, and thus may be more predictive of disease risk than individual foods or nutrients. In addition, there is growing evidence relating GI and/or GL to risks of obesity, type 2 diabetes as well as colon neoplasia. Therefore, we hypothesize that high dietary GL and/or GI, and/or a Western dietary pattern defined by a diverse array of dietary factors are associated with increased risk of colon polyps.

• investigate their potential joint actions [i.e., gene-diet and gene-gene]; 2) use a latent structural equation modeling approach to comprehensively evaluate these factors' potential direct as well as indirect (mediated by insulin resistance syndrome) impact, on colon polyps.

We will compare the immunohistochemistry of phosphorylated IRS1, AKT and mTOR in colon adenoma tissues with that in colon tissues from healthy control patients. Investigate the effect of obesity on the activation of the IRS1, AKT and mTOR by stratifying our cases and controls into lean and obese individuals. Evaluate the effects of serum levels of insulin, glucose, and insulin resistance index (HOMA-IR) on the activation of the IRS1, AKT and mTOR in colonic tissue.