Colorectal cancer is common in the United States and other Western countries. The biology of colorectal cancer provides unique opportunities for etiologic research. Because colorectal cancer arises from an ordered series of pathological precursor stages, epidemiologists can conduct studies that examine where various potential risk factors operate in the cancer sequence. This is a competing renewal application of a study that has been examining the epidemiologic aspects of colorectal cancer precursors for the past twelve years. The proposed study will explore the insulin-like growth factor (IGF) axis as it relates to events in rectal mucosa that lead to neoplasia. In so doing, the study will test a more mature set of hypotheses that link lifestyle and exposure information with specific endocrine and paracrine factors.
The specific aims of the study are: (1) To compare body weight (and anthropometric measures), glycemic load, and physical activity in patients with colorectal adenomas to adenoma-free controls. (2) To evaluate the association between circulating levels of IGF-I and IGF-II and adenomas/apoptosis. (3) To evaluate the association between circulating levels of IGF binding proteins IGFBP 1, IGFBP3 and adenomas/apoptosis. (4) To evaluate the association between tissue levels of IGF-I, IGF-II and IGFBP3 and adenomas/apoptosis. As a secondary aim the study will collect buffy coat specimens from blood. The white cell and tissue archive, combined with extensive exposure information, will provide a resource for future studies. Study subjects will be 400 consenting male and female patients who meet eligibility criteria. Rectal mucosal pinch biopsies will be taken during routine colonoscopy and immediately processed. Apoptosis will be measured using in-situ end-labeling and light microscopy. Circulating levels of IGF-axis hormones will be measured by ELISA. Tissue levels of IGF's and binding protein will be measured by quantitative competitive RT-PCR. The study is a logical extension of current research. The concept that lifestyle factors operate through endocrine and paracrine effects on the rectal mucosa has not been previously examined in comprehensive epidemiologic studies. By using meticulous laboratory methods, and by obtaining detailed information on diet and lifestyle, the proposed study has the potential to improve our understanding of mucosal factors associated with colorectal carcinogenesis.
| Jackson, John W; VanderWeele, Tyler J; Blacker, Deborah et al. (2015) Mediators of First- Versus Second-generation Antipsychotic-related Mortality in Older Adults. Epidemiology 26:700-9 |
| Keku, Temitope O; Dulal, Santosh; Deveaux, April et al. (2015) The gastrointestinal microbiota and colorectal cancer. Am J Physiol Gastrointest Liver Physiol 308:G351-63 |
| Mack, Christina DeFilippo; Brookhart, M Alan; Glynn, Robert J et al. (2015) Comparative Effectiveness of Oxaliplatin Versus 5-flourouricil in Older Adults: An Instrumental Variable Analysis. Epidemiology 26:690-9 |
| Murphy, Caitlin C; Martin, Christopher F; Sandler, Robert S (2015) Racial differences in obesity measures and risk of colorectal adenomas in a large screening population. Nutr Cancer 67:98-104 |
| Dulal, Santosh; Keku, Temitope O (2014) Gut microbiome and colorectal adenomas. Cancer J 20:225-31 |
| Santoro, M Agostina; Andres, Sarah F; Galanko, Joseph A et al. (2014) Reduced insulin-like growth factor I receptor and altered insulin receptor isoform mRNAs in normal mucosa predict colorectal adenoma risk. Cancer Epidemiol Biomarkers Prev 23:2093-100 |
| Nugent, Julia L; McCoy, Amber N; Addamo, Cassandra J et al. (2014) Altered tissue metabolites correlate with microbial dysbiosis in colorectal adenomas. J Proteome Res 13:1921-9 |
| Kang, Melissa; Peery, Anne F; Locklear, Cameron et al. (2013) Plasma insulin, glucose, IGF-I, IGF-II, and IGFBP-3 and risk of recurrent colorectal adenomas. J Gastroenterol Hepatol Res 2:531-535 |
| Frantz, David J; Crockett, Seth D; Galanko, Joseph A et al. (2013) Percent Body Fat Measured by Bioelectrical Impedance is Not Associated with Colorectal Adenoma Status. J Gastroenterol Hepatol Res 2:445-448 |
| Kang, Melissa; Edmundson, Patrick; Araujo-Perez, Felix et al. (2013) Association of plasma endotoxin, inflammatory cytokines and risk of colorectal adenomas. BMC Cancer 13:91 |
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