Current colorectal cancer screening modalities are not universally acceptable, and, for reasons of cost and low specificity, unlikely to be widely applied. To address the exigent need for further screening strategies, we propose to evaluate a biologically based screening approach that will incorporate a variety of cellular and molecular pathways to neoplasia. The focus of this project-and the entire P01- is on oxidative damage and apoptosis. Additionally, several pathways that are unique to colorectal carcinogenesis will be evaluated as possible targets for early detection efforts. Both human and animal studies will be conducted. To identify markers that discriminate patients with adenomas, hyperplastic polyps, ulcerative colitis, and adenocarcinomas from healthy controls, we propose to collect a variety of biologic materials (blood, colonic biopsies, primary lesions, rectal brushings, stool) and risk factor information on Group Health Cooperative of Puget Sound patients (n=800) undergoing clinically indicated colonoscopy. Specimens from individuals in each of the diagnostic categories will be evaluated for: specific markers of oxidative damage; aberrations in apoptosis proteins (bcl-2, bcl-x, bax); glutathione and GST expression; hypermethylation of the estrogen receptor gene; abnormalities in cell proliferation (Ki-67); and aspects of cell-cell interaction (connexins and E-cadherin). Analyses will explore the sensitivity and specificity of each of this group of biologically relevant markers that represent several pathways to carcinogens, with the goal of establishing an ensemble of markers that can facilitate the identification of individuals carrying neoplastic and pre-neoplastic lesions. Ultimately, we plan to evaluate the efficacy of screening using these markers in a prospective screening trial, which we will plan for the P01 renewal.
| Passarelli, Michael N; Newcomb, Polly A; Makar, Karen W et al. (2015) Blood lipids and colorectal polyps: testing an etiologic hypothesis using phenotypic measurements and Mendelian randomization. Cancer Causes Control 26:467-73 |
| Adams, Scott V; Newcomb, Polly A; Burnett-Hartman, Andrea N et al. (2014) Rare circulating microRNAs as biomarkers of colorectal neoplasia. PLoS One 9:e108668 |
| Burnett-Hartman, Andrea N; Newcomb, Polly A; Hutter, Carolyn M et al. (2014) Variation in the association between colorectal cancer susceptibility loci and colorectal polyps by polyp type. Am J Epidemiol 180:223-32 |
| Burnett-Hartman, Andrea N; Newcomb, Polly A; Potter, John D et al. (2013) Genomic aberrations occurring in subsets of serrated colorectal lesions but not conventional adenomas. Cancer Res 73:2863-72 |
| Burnett-Hartman, Andrea N; Passarelli, Michael N; Adams, Scott V et al. (2013) Differences in epidemiologic risk factors for colorectal adenomas and serrated polyps by lesion severity and anatomical site. Am J Epidemiol 177:625-37 |
| Burnett-Hartman, Andrea N; Newcomb, Polly A; Phipps, Amanda I et al. (2012) Colorectal endoscopy, advanced adenomas, and sessile serrated polyps: implications for proximal colon cancer. Am J Gastroenterol 107:1213-9 |
| Burnett-Hartman, Andrea N; Newcomb, Polly A; Mandelson, Margaret T et al. (2011) No evidence for human papillomavirus in the etiology of colorectal polyps. Cancer Epidemiol Biomarkers Prev 20:2288-97 |
| Adams, Scott V; Newcomb, Polly A; Burnett-Hartman, Andrea N et al. (2011) Circulating 25-hydroxyvitamin-D and risk of colorectal adenomas and hyperplastic polyps. Nutr Cancer 63:319-26 |
| Chia, Victoria M; Newcomb, Polly A; Lampe, Johanna W et al. (2007) Leptin concentrations, leptin receptor polymorphisms, and colorectal adenoma risk. Cancer Epidemiol Biomarkers Prev 16:2697-703 |
| O'Sullivan, Jacintha; Risques, Rosa Ana; Mandelson, Margaret T et al. (2006) Telomere length in the colon declines with age: a relation to colorectal cancer? Cancer Epidemiol Biomarkers Prev 15:573-7 |
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