|Grant Number:||5R01CA151993-03 Interpret this number|
|Primary Investigator:||Ogino, Shuji|
|Organization:||Dana-Farber Cancer Inst|
|Project Title:||Epigenetic Events and Colorectal Cancer Epidemiology|
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.
Lifecourse Epidemiology and Molecular Pathological Epidemiology.
Authors: Nishi A, Kawachi I, Koenen KC, Wu K, Nishihara R, Ogino S
Source: Am J Prev Med, 2015 Jan;48(1), p. 116-119.
Alcohol, one-carbon nutrient intake, and risk of colorectal cancer according to tumor methylation level of IGF2 differentially methylated region.
Authors: Nishihara R, Wang M, Qian ZR, Baba Y, Yamauchi M, Mima K, Sukawa Y, Kim SA, Inamura K, Zhang X, Wu K, Giovannucci EL, Chan AT, Fuchs CS, Ogino S, Schernhammer ES
Source: Am J Clin Nutr, 2014 Dec;100(6), p. 1479-88.
EPub date: 2014 Oct 8.
RNF43 is frequently mutated in colorectal and endometrial cancers.
Authors: Giannakis M, Hodis E, Jasmine Mu X, Yamauchi M, Rosenbluh J, Cibulskis K, Saksena G, Lawrence MS, Qian ZR, Nishihara R, Van Allen EM, Hahn WC, Gabriel SB, Lander ES, Getz G, Ogino S, Fuchs CS, Garraway LA
Source: Nat Genet, 2014 Dec;46(12), p. 1264-6.
EPub date: 2014 Oct 26.
Red Meat Intake, NAT2, and Risk of Colorectal Cancer: A Pooled Analysis of 11 Studies.
Authors: Ananthakrishnan AN, Du M, Berndt SI, Brenner H, Caan BJ, Casey G, Chang-Claude J, Duggan D, Fuchs CS, Gallinger S, Giovannucci EL, Harrison TA, Hayes RB, Hoffmeister M, Hopper JL, Hou L, Hsu L, Jenkins MA, Kraft P, Ma J, Nan H, Newcomb PA, Ogino S, Potter JD, Seminara D, Slattery ML, Thornquist M, White E, Wu K, Peters U, Chan AT
Source: Cancer Epidemiol Biomarkers Prev, 2015 Jan;24(1), p. 198-205.
EPub date: 2014 Oct 23.
Prognostic Significance and Molecular Features of Signet-Ring Cell and Mucinous Components in Colorectal Carcinoma.
Authors: Inamura K, Yamauchi M, Nishihara R, Kim SA, Mima K, Sukawa Y, Li T, Yasunari M, Zhang X, Wu K, Meyerhardt JA, Fuchs CS, Harris CC, Qian ZR, Ogino S
Source: Ann Surg Oncol, 2014 Oct 18;null, p. null.
EPub date: 2014 Oct 18.
Challenges and opportunities in international molecular cancer prevention research: An ASPO Molecular Epidemiology and the Environment and International Cancer Prevention Interest Groups Report.
Authors: Epplein M, Bostick RM, Mu L, Ogino S, Braithwaite D, Kanetsky PA
Source: Cancer Epidemiol Biomarkers Prev, 2014 Nov;23(11), p. 2613-7.
EPub date: 2014 Oct 2.
Tumor LINE-1 methylation level and microsatellite instability in relation to colorectal cancer prognosis.
Authors: Inamura K, Yamauchi M, Nishihara R, Lochhead P, Qian ZR, Kuchiba A, Kim SA, Mima K, Sukawa Y, Jung S, Zhang X, Wu K, Cho E, Chan AT, Meyerhardt JA, Harris CC, Fuchs CS, Ogino S
Source: J Natl Cancer Inst, 2014 Sep;106(9), p. null.
EPub date: 2014 Sep 4.
IGF2 differentially methylated region hypomethylation in relation to pathological and molecular features of serrated lesions.
Authors: Naito T, Nosho K, Ito M, Igarashi H, Mitsuhashi K, Yoshii S, Aoki H, Nomura M, Sukawa Y, Yamamoto E, Adachi Y, Takahashi H, Hosokawa M, Fujita M, Takenouchi T, Maruyama R, Suzuki H, Baba Y, Imai K, Yamamoto H, Ogino S, Shinomura Y
Source: World J Gastroenterol, 2014 Aug 7;20(29), p. 10050-61.
SMO expression in colorectal cancer: associations with clinical, pathological, and molecular features.
Authors: Li T, Liao X, Lochhead P, Morikawa T, Yamauchi M, Nishihara R, Inamura K, Kim SA, Mima K, Sukawa Y, Kuchiba A, Imamura Y, Baba Y, Shima K, Meyerhardt JA, Chan AT, Fuchs CS, Ogino S, Qian ZR
Source: Ann Surg Oncol, 2014 Dec;21(13), p. 4164-73.
EPub date: 2014 Jul 15.
Progress and opportunities in molecular pathological epidemiology of colorectal premalignant lesions.
Authors: Lochhead P, Chan AT, Giovannucci E, Fuchs CS, Wu K, Nishihara R, O'Brien M, Ogino S
Source: Am J Gastroenterol, 2014 Aug;109(8), p. 1205-14.
EPub date: 2014 Jun 17.
Etiologic field effect: reappraisal of the field effect concept in cancer predisposition and progression.
Authors: Lochhead P, Chan AT, Nishihara R, Fuchs CS, Beck AH, Giovannucci E, Ogino S
Source: Mod Pathol, 2015 Jan;28(1), p. 14-29.
EPub date: 2014 Jun 13.
Predicted 25(OH)D score and colorectal cancer risk according to vitamin D receptor expression.
Authors: Jung S, Qian ZR, Yamauchi M, Bertrand KA, Fitzgerald KC, Inamura K, Kim SA, Mima K, Sukawa Y, Zhang X, Wang M, Smith-Warner SA, Wu K, Fuchs CS, Chan AT, Giovannucci EL, Ng K, Cho E, Ogino S, Nishihara R
Source: Cancer Epidemiol Biomarkers Prev, 2014 Aug;23(8), p. 1628-37.
EPub date: 2014 Jun 11.
Analyses of clinicopathological, molecular, and prognostic associations of KRAS codon 61 and codon 146 mutations in colorectal cancer: cohort study and literature review.
Authors: Imamura Y, Lochhead P, Yamauchi M, Kuchiba A, Qian ZR, Liao X, Nishihara R, Jung S, Wu K, Nosho K, Wang YE, Peng S, Bass AJ, Haigis KM, Meyerhardt JA, Chan AT, Fuchs CS, Ogino S
Source: Mol Cancer, 2014 May 31;13, p. 135.
EPub date: 2014 May 31.
Urinary PGE-M levels are associated with risk of colorectal adenomas and chemopreventive response to anti-inflammatory drugs.
Authors: Bezawada N, Song M, Wu K, Mehta RS, Milne GL, Ogino S, Fuchs CS, Giovannucci EL, Chan AT
Source: Cancer Prev Res (Phila), 2014 Jul;7(7), p. 758-65.
EPub date: 2014 May 13.
Aspirin and the risk of colorectal cancer in relation to the expression of 15-hydroxyprostaglandin dehydrogenase (HPGD).
Authors: Fink SP, Yamauchi M, Nishihara R, Jung S, Kuchiba A, Wu K, Cho E, Giovannucci E, Fuchs CS, Ogino S, Markowitz SD, Chan AT
Source: Sci Transl Med, 2014 Apr 23;6(233), p. 233re2.
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;106(4), p. dju016.
EPub date: 2014 Feb 24.