DF/HCC Program Affiliation

Cancer Epidemiology
Gastrointestinal Malignancies

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

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