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Discovering the causes of cancer and the means of prevention
 

DCEG Award Recipients - Anand Pathak, MD, PhD, MPH, Olusegun Onabajo, PhD, Clara Lam, PhD, MPH

DCEG Events

April 16, 2015 | 10:30 AM – 11:30 AM

NCI Shady Grove

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Title: Translational Application of GWAS Data: The Potential of the Testicular Cancer Polygenic Risk Score

Anand Pathak, M.D., Ph.D., M.P.H., Postdoctoral Fellow
Recipient of the: 2015 DCEG Fellows Awards for Research Excellence (D-FARE) AND 2014 Intramural Research Award

Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics 
National Cancer Institute

Description:  Testicular germ cell tumors (TGCT) have an estimated heritability that ranks as the 3rd highest for all cancers. Despite this, two genome-wide genetic linkage studies did not uncover any major, highly-penetrant genes predisposing to TGCT. Instead, TGCT risk appears to be driven by multiple genetic loci. To investigate this, we were the first group to generate a polygenic risk score (PRS) for testicular cancer. The PRS score was constructed as the weighted sum of the risk allele counts for a locus multiplied by the log odds ratio of its association with testicular cancer for 21 independent SNPs from 18 GWAS loci. We demonstrated the effectiveness of the PRS in distinguishing cases from controls in three cohorts. There are limited metrics (microlithiasis, undescended testis) to predict risk in a man with a family history of testicular cancer. We showed, for the first time in testicular cancer, the potential of the PRS to translate GWAS findings into a clinically useful tool for cancer risk stratification.

Title: Interferon lambda 4 (IFN-λ4), a novel interferon created by a common genetic variant: how does it interfere with clearance of hepatitis C virus?

Olusegun (Segun) Onabajo, Ph.D., Postdoctoral Fellow
Recipient of the 2015 DCEG Fellows Awards for Research Excellence (D-FARE)
Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics

Description:  Recently we discovered and characterized interferon lambda 4 (IFN-λ4), a novel type-III interferon. A frame-shift allele (dG) of an exonic genetic variant (rs368234815-dG/TT), which creates IFN-λ4 in carriers of this allele, is the strongest host factor associated with decreased clearance of HCV, spontaneously or after treatment.   More than 3% of the world population is infected with hepatitis C virus (HCV). Of all acutely infected individuals, 80% fail to clear the virus and develop chronic HCV infection, which is a significant cause of hepatocellular carcinoma.

To understand the role of IFN-λ4 during HCV infection, we performed detailed functional analysis of IFN-λ4. We suggest that a pathogenic effect of IFN-λ4 expression in human hepatic cells is associated with inhibition of cell proliferation causing increased cell death and induction of pro-inflammatory cytokines. Chronic induction of IFN-λ4 in HCV-infected hepatocytes leading to cell death and tissue repair may result in hepatic fibrosis and cirrhosis, which are relevant factors affecting clearance of HCV and, possibly progression to hepatocellular carcinoma.

AND

Title: Identifying risk factors for second melanoma among survivors of non-Hodgkin lymphoma in SEER-Medicare

Clara Kim Lam, Ph.D., M.P.H., Postdoctoral Fellow
Recipient of the 2015 DCEG Fellows Awards for Research Excellence (D-FARE)
Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics

Description: Previous studies have reported that non-Hodgkin lymphoma (NHL) survivors have an increased risk of developing cutaneous melanoma, however, risks associated with specific treatments and immune-related risk factors have not been quantified.  Second malignancies are a major cause of morbidity and mortality among NHL survivors, thus understanding second malignancy etiology can provide important clinical information and insight into carcinogenesis.  Dr. Lam will present results providing understanding of the contributions of cancer treatments (chemotherapy, radiotherapy) and medical history risk factors (autoimmune conditions, infections) to second melanoma etiology in adult NHL survivors using the SEER-Medicare database.