DF/HCC Program Affiliation

Member, Cancer Epidemiology Program
Member, Gastrointestinal Malignancies Program

Research Abstract

I am conducting molecular epidemiologic research on colorectal and pancreatic cancers utilizing two large prospective cohorts, Nurses' Health Study (NHS) and Health Professionals Follow-up Study (HPFS) (N=121,700 and N=51,500, when the studies began in 1976 and 1986, respectively), in collaborations with Harvard School of Public Health and Channing Laboratory of the Brigham and Women’s Hospital. My primary research interests are: (1) to detect molecular alterations in colorectal cancer in these cohorts; (2) to investigate how exogenous modifiable factors (lifestyle factors such as diet, alcohol, smoking, exercise, aspirin intake, etc.) cause specific molecular alterations in cells during cancer development; and (3) to examine combined effects of exogenous factors and specific molecular alterations in tumor on patient survival. Therefore, we try to link molecular changes in cancer cells, modifiable lifestyle factors, and mechanisms of aggressive behavior of cancer. Unifying these areas could substantially enhance our understanding of colorectal cancer development and behavior, and ultimately help us decrease colorectal cancer cases and deaths. To accomplish these aims, I perform a number of assays to characterize molecular features of tumor. I have been conducting quantitative DNA methylation analysis using MethyLight on a panel of 8 gene promoters to determine CpG island methylator phenotype (CIMP) of colorectal cancer, and using Pyrosequencing to measure LINE-1 methylation as a surrogate marker for genome-wide DNA methylation level. I analyze KRAS, BRAF and PIK3CA mutations in tumors by Pyrosequencing technology, and perform microsatellite instability (MSI) analysis by a 10-marker panel, and LOH analyses on 18q. I also perform immunohistochemical analyses for TP53, CDKN1A (p21), CDKN1B (p27), CDKN2A (p16), PTGS2 (COX2), FASN, MGMT, MLH1, MSH2, CTNNB1 (beta-catenin), CCND1 (cyclin D1), and p-RPS6, using tissue microarrays (TMAs).

Publications

• Ogino S, Goel A. Molecular classification and correlates in colorectal cancer. J Mol Diagn 2008 Jan; 10(1):13-27
  PMID: 18165277
• Kawasaki T, Nosho K, Ohnishi M, Suemoto Y, Kirkner GJ, Fuchs CS, Ogino S. IGFBP3 promoter methylation in colorectal cancer: relationship with microsatellite instability, CpG island methylator phenotype, and p53. Neoplasia 2007 Dec; 9(12):1091-8
  PMID: 18084616
• Ogino S, Hazra A, Tranah GJ, Kirkner GJ, Kawasaki T, Nosho K, Ohnishi M, Suemoto Y, Meyerhardt JA, Hunter DJ, Fuchs CS. MGMT germline polymorphism is associated with somatic MGMT promoter methylation and gene silencing in colorectal cancer. Carcinogenesis 2007 Jul 9;
  PMID: 17621591
• Chan AT, Ogino S, Fuchs CS. Aspirin and the Risk of Colorectal Cancer in Relation to the Expression of COX-2. N Engl J Med 2007 May 24; 356(21):2131-2142
  PMID: 17522398
• Ogino S, Kawasaki T, Kirkner GJ, Kraft P, Loda M, Fuchs CS. Evaluation of Markers for CpG Island Methylator Phenotype (CIMP) in Colorectal Cancer by a Large Population-Based Sample. J Mol Diagn 2007 May 3;
  PMID: 17478565
• Ogino S, Kawasaki T, Kirkner GJ, Suemoto Y, Meyerhardt JA, Fuchs CS. Molecular correlates with MGMT promoter methylation and silencing support CpG island methylator phenotype-low (CIMP-low) in colorectal cancer. Gut 2007 Mar 5;
  PMID: 17339237
• Ogino S, Gulley ML, den Dunnen JT, Wilson RB. Standard Mutation Nomenclature in Molecular Diagnostics: Practical and Educational Challenges. J Mol Diagn 2007 Feb; 9(1):1-6
  PMID: 17251329
• Chan AT, Ogino S, Fuchs CS. Aspirin use and risk of colorectal cancer according to cyclooxygenase-2 expression Eval & Prog Plan 2007; ?:in press
  PMID: 0
• Ogino S, Kawasaki T, Kirkner GJ, Kraft P, Loda M, Fuchs CS. Evaluation of markers for CpG island methylator phenotype (CIMP) in colorectal cancer using a large population-based sample J Mol Diagn 2007; 9:in press
  PMID: 0
• Ogino S, Kawasaki T, Kirkner GJ, Kraft P, Loda M, Fuchs CS. Evaluation of markers for CpG island methylator phenotype (CIMP) in colorectal cancer using a large population-based sample J Mol Diagn 2007; 9:in press
  PMID: 0
• Chan AT, Ogino S, Fuchs CS. Aspirin use and risk of colorectal cancer according to cyclooxygenase-2 expression Eval & Prog Plan 2007; ?:in press
  PMID: 0
• Ogino S, Kawasaki T, Kirkner GJ, Kraft P, Loda M, Fuchs CS. Evaluation of markers for CpG island methylator phenotype (CIMP) in colorectal cancer using a large population-based sample J Mol Diagn 2007; 9:in press
  PMID: 0
• Ogino S, Kawasaki T, Kirkner GJ, Kraft P, Loda M, Fuchs CS. Evaluation of markers for CpG island methylator phenotype (CIMP) in colorectal cancer using a large population-based sample J Mol Diagn 2007; 9:in press
  PMID: 0
• Chan AT, Ogino S, Fuchs CS. Aspirin use and risk of colorectal cancer according to cyclooxygenase-2 expression Eval & Prog Plan 2007; ?:in press
  PMID: 0
• Ogino S, Kawasaki T, Kirkner GJ, Kraft P, Loda M, Fuchs CS. Evaluation of markers for CpG island methylator phenotype (CIMP) in colorectal cancer using a large population-based sample J Mol Diagn 2007; 9:in press
  PMID: 0
• Ogino S, Kawasaki T, Kirkner GJ, Kraft P, Loda M, Fuchs CS. Evaluation of markers for CpG island methylator phenotype (CIMP) in colorectal cancer using a large population-based sample J Mol Diagn 2007; 9:in press
  PMID: 0
• Ogino S, Kawasaki T, Kirkner GJ, Yamaji T, Loda M, Fuchs CS. Loss of nuclear p27 (CDKN1B/KIP1) in colorectal cancer is correlated with microsatellite instability and CIMP. Mod Pathol 2007 Jan; 20(1):15-22
  PMID: 17086168
• Ogino S, Odze RD, Kawasaki T, Brahmandam M, Kirkner GJ, Laird PW, Loda M, Fuchs CS. Correlation of pathologic features with CpG island methylator phenotype (CIMP) by quantitative DNA methylation analysis in colorectal carcinoma. Am J Surg Pathol 2006 Sep; 30(9):1175-83
  PMID: 16931963
• Ogino S, Kawasaki T, Kirkner G, Ogawa A, Dorfman I, Loda M, Fuchs C. Down-regulation of p21 (CDKN1A/CIP1) is inversely associated with microsatellite instability and CpG island methylator phenotype (CIMP) in colorectal cancer. J Pathol 2006 Jul 19;
  PMID: 16850502
• Ogino S, Kawasaki T, Brahmandam M, Cantor M, Kirkner GJ, Spiegelman D, Makrigiorgos GM, Weisenberger DJ, Laird PW, Loda M, Fuchs CS. Precision and Performance Characteristics of Bisulfite Conversion and Real-Time PCR (MethyLight) for Quantitative DNA Methylation Analysis. J Mol Diagn 2006 May; 8(2):209-217
  PMID: 16645207
• Ogino S, Cantor M, Kawasaki T, Brahmandam M, Kirkner G, Weisenberger DJ, Campan M, Laird PW, Loda M, Fuchs CS. CpG island methylator phenotype (CIMP) of colorectal cancer is best characterized by quantitative DNA methylation analysis and prospective cohort studies. Gut 2006 Jan 11;
  PMID: 16407376
• Giovannucci E, Ogino S. DNA methylation, field effects, and colorectal cancer. J Natl Cancer Inst 2005 Sep 21; 97(18):1317-9
  PMID: 16174847
• Ogino S, Meyerhardt JA, Cantor M, Brahmandam M, Clark JW, Namgyal C, Kawasaki T, Kinsella K, Michelini AL, Enzinger PC, Kulke MH, Ryan DP, Loda M, Fuchs CS. Molecular alterations in tumors and response to combination chemotherapy with gefitinib for advanced colorectal cancer. Clin Cancer Res 2005 Sep 15; 11(18):6650-6
  PMID: 16166444
• Ogino S, Wilson RB. Bayesian analysis and risk assessment in genetic counseling and testing. J Mol Diagn 2004 Feb; 6(1):1-9
  PMID: 14736820
• Ogino S, Wilson RB. Genotype and haplotype distributions of MTHFR677C>T and 1298A>C single nucleotide polymorphisms: a meta-analysis. J Hum Genet 2003; 48(1):1-7
  PMID: 12560871
• Ogino S, Wilson RB. Genetic testing and risk assessment for spinal muscular atrophy (SMA). Hum Genet 2002 Dec; 111(6):477-500
  PMID: 12436240