According to current clinical practice guidelines, hyperplastic polyps are benign lesions that can be safely ignored. However, recent evidence suggests that hyperplastic polyps, a common finding in nearly 30% of adults, may indeed be pre-neoplastic lesions. While only a minority of hyperplastic polyps progress to malignancy, the characteristics of those at-risk lesions are not fully known. In molecular terms, the presence of microsatellite instability (MSI) and/or CpG island methylation (CIMP) may be the hallmark of hyperplastic polyps that give rise to sporadic colorectal carcinomas. In this emerging paradigm, there is a great need to confirm these findings on a well-characterized sample, and more importantly, to understand the environmental and genetic characteristics that are associated with hyperplastic polyps, particularly in comparison to the better understood adenomas. To investigate the relationship between risk factors, epigenetic characteristics, and polyps, we propose to conduct a population based case-control study of hyperplastic polyps, adenomatous polyps, and normal controls. Individuals with a new diagnosis of polyps (hyperplastic polyps n=700, adenomas n=700) will be identified by a centralized review of the pathology files of Group Health Cooperative (GHC) of Puget Sound a large health maintenance organization. Similarly aged individuals with normal screening colonoscopies (n=700) will be identified from procedure files. All subjects will complete a standardized interview and provide a buccal sample. The diagnostic materials of all cases will be reviewed, DNA extracted from lesional blocks, and MSI and CIMP status will be assessed using standard panels of markers. Polymorphisms in epoxide hydrolase (mEH), which are involved in the detoxification of polyaromatic hydrocarbons in smoke and cooked meat, will be evaluated for their modifying effect on environmental exposures. This study will provide the largest study of risk factors for hyperplastic polyps, their genetic characterization, and comparisons to adenomas and normals. In this study neoplastic pathways will be classified on the basis of genetic instability, DNA methylation phenotype, and epidemiologic risk factors. The results of this study will have implications for understanding the biology and prevention of colorectal cancer.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
1R01CA097325-01A2
Application #
6723317
Study Section
Epidemiology and Disease Control Subcommittee 2 (EDC)
Program Officer
Starks, Vaurice
Project Start
2004-05-17
Project End
2009-04-30
Budget Start
2004-05-17
Budget End
2005-04-30
Support Year
1
Fiscal Year
2004
Total Cost
$527,307
Indirect Cost
Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
078200995
City
Seattle
State
WA
Country
United States
Zip Code
98109
Hardikar, Sheetal; Burnett-Hartman, Andrea N; Phipps, Amanda I et al. (2018) Telomere length differences between colorectal polyp subtypes: a colonoscopy-based case-control study. BMC Cancer 18:513
Hardikar, Sheetal; Burnett-Hartman, Andrea N; Chubak, Jessica et al. (2017) Reproductive factors and risk of colorectal polyps in a colonoscopy-based study in western Washington State. Cancer Causes Control 28:241-246
Passarelli, Michael N; Newcomb, Polly A (2016) Blood Lipid Concentrations and Colorectal Adenomas: A Systematic Review and Meta-Analysis of Colonoscopy Studies in Asia, 2000-2014. Am J Epidemiol 183:691-700
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
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) Colorectal polyp type and the association with charred meat consumption, smoking, and microsomal epoxide hydrolase polymorphisms. Nutr Cancer 63:583-92
Wernli, Karen J; Newcomb, Polly A; Wang, Yinghui et al. (2010) Body size, IGF and growth hormone polymorphisms, and colorectal adenomas and hyperplastic polyps. Growth Horm IGF Res 20:305-9

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