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Grant Details

Grant Number: 5R01CA151993-03 Interpret this number
Primary Investigator: Ogino, Shuji
Organization: Dana-Farber Cancer Inst
Project Title: Epigenetic Events and Colorectal Cancer Epidemiology
Fiscal Year: 2012
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Abstract

DESCRIPTION (provided by applicant): As the first independent application led by a recipient of NCI K07 Award ("Molecular Epidemiology of Colorectal Cancer"), this proposal addresses hypotheses in epigenetics and epidemiology of colorectal cancer, in response to NIH Program Announcement PA- 09-234 ("Diet, Epigenetic Events, and Cancer Prevention"). Colorectal cancer is the second leading cause of cancer death in the United States. Abnormal DNA methylation patterns are a hallmark of most cancers including colorectal cancer. Furthermore, DNA methylation alterations (such as loss of imprinting) in non-cancerous cells may predispose to cancer development. Importantly, epigenetic changes, including DNA methylation alterations, are reversible and thus can be targets for therapy or chemoprevention. Accumulating evidence suggests that dietary factors (e.g., alcohol and one-carbon nutrients such as B vitamins) may affect cellular epigenetic status. Examining how dietary factors influence epigenetic alterations is important for better understanding of colorectal cancer development and progression, which can provide a scientific basis for dietary recommendations and help optimize preventive strategies. For that purpose, we will utilize the resources of two large prospective cohort studies, the Nurses' Health Study (NHS) and the Health Professionals Follow-up Study (HPFS). Both cohort studies provide dietary data over a 20-year period, DNA from blood cells, long-term survival data, and paraffin-embedded tissue of colorectal cancers. We anticipate over 4500 incident colorectal cancer cases up to 2012 in these cohorts, and among those, paraffin-embedded tissue materials will be available in over 3000 cases. We propose to examine the interrelationship between intake of dietary one-carbon nutrients and alcohol, colorectal cancer risk, cellular epigenetic changes, and clinical outcome. In addition, we will utilize data resulting from genome-wide expression profiling of 1000 colorectal cancers in the cohorts (which has been ongoing with separate funding supports) to discover genes potentially related to abnormal one-carbon metabolism as well as specific epigenomic aberrations in colorectal cancer. Thus, we are in a unique position to examine the relations between modifiable dietary factors, epigenetic and epigenomic aberrations, and genome-wide expression patterns in tumor cells. Through better understanding of epigenetic mechanisms of carcinogenesis, we can propose preventive measures for the incidence and mortality from colorectal cancer. PUBLIC HEALTH RELEVANCE: Prevention of colorectal cancer occurrence and mortality is of great public interest, because approximately 140,000 Americans develop colorectal cancer and approximately 50,000 individuals die from the disease every year. We propose to examine the relations between modifiable dietary factors, colorectal cancer risk, cellular epigenetic changes, and patient survival. Through better understanding of epigenetic mechanisms of colorectal cancer development and progression, we can provide a scientific basis for dietary recommendations and help optimize preventive strategies.

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Publications

A Prospective Study of Macrophage Inhibitory Cytokine-1 (MIC-1/GDF15) and Risk of Colorectal Cancer.
Authors: Mehta RS, Song M, Bezawada N, Wu K, Garcia-Albeniz X, Morikawa T, Fuchs CS, Ogino S, Giovannucci EL, Chan AT
Source: J Natl Cancer Inst, 2014 Apr 1;106(4), p. dju016.
EPub date: 2014 Feb 24.
PMID: 24565956
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Total calcium intake and colorectal adenoma in young women.
Authors: Massa J, Cho E, Orav EJ, Willett WC, Wu K, Giovannucci EL
Source: Cancer Causes Control, 2014 Apr;25(4), p. 451-60.
EPub date: 2014 Feb 22.
PMID: 24562904
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An integrative analysis reveals functional targets of GATA6 transcriptional regulation in gastric cancer.
Authors: Sulahian R, Casey F, Shen J, Qian ZR, Shin H, Ogino S, Weir BA, Vazquez F, Liu XS, Hahn WC, Bass AJ, Chan V, Shivdasani RA
Source: Oncogene, 2013 Dec 9;null, p. null.
EPub date: 2013 Dec 9.
PMID: 24317510
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Aspirin use, 8q24 single nucleotide polymorphism rs6983267, and colorectal cancer according to CTNNB1 alterations.
Authors: Nan H, Morikawa T, Suuriniemi M, Imamura Y, Werner L, Kuchiba A, Yamauchi M, Hunter DJ, Kraft P, Giovannucci EL, Fuchs CS, Ogino S, Freedman ML, Chan AT
Source: J Natl Cancer Inst, 2013 Dec 18;105(24), p. 1852-61.
EPub date: 2013 Dec 7.
PMID: 24317174
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Predictive and prognostic analysis of PIK3CA mutation in stage III colon cancer intergroup trial.
Authors: Ogino S, Liao X, Imamura Y, Yamauchi M, McCleary NJ, Ng K, Niedzwiecki D, Saltz LB, Mayer RJ, Whittom R, Hantel A, Benson AB 3rd, Mowat RB, Spiegelman D, Goldberg RM, Bertagnolli MM, Meyerhardt JA, Fuchs CS, Alliance for Clinical Trials in Oncology
Source: J Natl Cancer Inst, 2013 Dec 4;105(23), p. 1789-98.
EPub date: 2013 Nov 14.
PMID: 24231454
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Long-term use of multivitamins and risk of colorectal adenoma in women.
Authors: Massa J, Cho E, Orav EJ, Willett WC, Wu K, Giovannucci EL
Source: Br J Cancer, 2014 Jan 7;110(1), p. 249-55.
EPub date: 2013 Nov 12.
PMID: 24220696
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Long-term colorectal-cancer incidence and mortality after lower endoscopy.
Authors: Nishihara R, Wu K, Lochhead P, Morikawa T, Liao X, Qian ZR, Inamura K, Kim SA, Kuchiba A, Yamauchi M, Imamura Y, Willett WC, Rosner BA, Fuchs CS, Giovannucci E, Ogino S, Chan AT
Source: N Engl J Med, 2013 Sep 19;369(12), p. 1095-105.
PMID: 24047059
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Microsatellite instability and BRAF mutation testing in colorectal cancer prognostication.
Authors: Lochhead P, Kuchiba A, Imamura Y, Liao X, Yamauchi M, Nishihara R, Qian ZR, Morikawa T, Shen J, Meyerhardt JA, Fuchs CS, Ogino S
Source: J Natl Cancer Inst, 2013 Aug 7;105(15), p. 1151-6.
EPub date: 2013 Jul 22.
PMID: 23878352
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Plasma adiponectin and soluble leptin receptor and risk of colorectal cancer: a prospective study.
Authors: Song M, Zhang X, Wu K, Ogino S, Fuchs CS, Giovannucci EL, Chan AT
Source: Cancer Prev Res (Phila), 2013 Sep;6(9), p. 875-85.
EPub date: 2013 Jul 19.
PMID: 23872505
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Anatomic subsite of primary colorectal cancer and subsequent risk and distribution of second cancers.
Authors: Phipps AI, Chan AT, Ogino S
Source: Cancer, 2013 Sep 1;119(17), p. 3140-7.
EPub date: 2013 Jul 15.
PMID: 23856984
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Aspirin use and risk of colorectal cancer according to BRAF mutation status.
Authors: Nishihara R, Lochhead P, Kuchiba A, Jung S, Yamauchi M, Liao X, Imamura Y, Qian ZR, Morikawa T, Wang M, Spiegelman D, Cho E, Giovannucci E, Fuchs CS, Chan AT, Ogino S
Source: JAMA, 2013 Jun 26;309(24), p. 2563-71.
PMID: 23800934
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Discovery of colorectal cancer PIK3CA mutation as potential predictive biomarker: power and promise of molecular pathological epidemiology.
Authors: Ogino S, Lochhead P, Giovannucci E, Meyerhardt JA, Fuchs CS, Chan AT
Source: Oncogene, 2013 Jun 24;null, p. null.
EPub date: 2013 Jun 24.
PMID: 23792451
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A prospective study of duration of smoking cessation and colorectal cancer risk by epigenetics-related tumor classification.
Authors: Nishihara R, Morikawa T, Kuchiba A, Lochhead P, Yamauchi M, Liao X, Imamura Y, Nosho K, Shima K, Kawachi I, Qian ZR, Fuchs CS, Chan AT, Giovannucci E, Ogino S
Source: Am J Epidemiol, 2013 Jul 1;178(1), p. 84-100.
EPub date: 2013 Jun 20.
PMID: 23788674
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Physical activity, tumor PTGS2 expression, and survival in patients with colorectal cancer.
Authors: Yamauchi M, Lochhead P, Imamura Y, Kuchiba A, Liao X, Qian ZR, Nishihara R, Morikawa T, Shima K, Wu K, Giovannucci E, Meyerhardt JA, Fuchs CS, Chan AT, Ogino S
Source: Cancer Epidemiol Biomarkers Prev, 2013 Jun;22(6), p. 1142-52.
EPub date: 2013 Apr 29.
PMID: 23629521
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A prospective study of plasma inflammatory markers and risk of colorectal cancer in men.
Authors: Song M, Wu K, Ogino S, Fuchs CS, Giovannucci EL, Chan AT
Source: Br J Cancer, 2013 May 14;108(9), p. 1891-8.
EPub date: 2013 Apr 16.
PMID: 23591192
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Exome and whole-genome sequencing of esophageal adenocarcinoma identifies recurrent driver events and mutational complexity.
Authors: Dulak AM, Stojanov P, Peng S, Lawrence MS, Fox C, Stewart C, Bandla S, Imamura Y, Schumacher SE, Shefler E, McKenna A, Carter SL, Cibulskis K, Sivachenko A, Saksena G, Voet D, Ramos AH, Auclair D, Thompson K, Sougnez C, Onofrio RC, Guiducci C, Beroukhim R, Zhou Z, Lin L, Lin J, Reddy R, Chang A, Landrenau R, Pennathur A, Ogino S, Luketich JD, Golub TR, Gabriel SB, Lander ES, Beer DG, Godfrey TE, Getz G, Bass AJ
Source: Nat Genet, 2013 May;45(5), p. 478-86.
EPub date: 2013 Mar 24.
PMID: 23525077
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Prospective analysis of body mass index, physical activity, and colorectal cancer risk associated with ?-catenin (CTNNB1) status.
Authors: Morikawa T, Kuchiba A, Lochhead P, Nishihara R, Yamauchi M, Imamura Y, Liao X, Qian ZR, Ng K, Chan AT, Meyerhardt JA, Giovannucci E, Fuchs CS, Ogino S
Source: Cancer Res, 2013 Mar 1;73(5), p. 1600-10.
EPub date: 2013 Feb 26.
PMID: 23442321
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