Public Release: 

JNCI tip sheet -- June 17

Journal of the National Cancer Institute

Polyomavirus Infection in Merkel Cell Carcinoma Is Associated with Better Outcomes

A polyomavirus known as MCPyV is associated with clinical outcomes, including fewer metastases and better survival, in patients with a rare form of skin cancer called Merkel cell carcinoma, according to a new study published online June 17 in the JNCI.

Integration of the Merkel cell carcinoma polyomavirus (MCPyV) genome into the tumor genome was recently found to be frequent in skin cancers, but the clinical consequences of MVPyV genomic integration was unclear.

To examine the consequences of viral DNA integration, Heikki Joensuu, M.D., of the Department of Oncology at Helsinki University Central Hospital, and colleagues, conducted histopathologic and molecular biological analyses of tumor tissue and DNA from 109 Finnish patients who were diagnosed with Merkel cell carcinoma from 1979 to 2004.

Approximately 50% of the tumors were positive for MCPyV DNA. These cancers tended to be located in a limb, to have less frequent nodal or distant metastases at the time of diagno¬sis, and to be associated with better survival compared with MCPyV DNA-negative cancers.

"Identification of MCPyV as a contributing factor to the pathogenesis of Merkel cell carcinoma might provide novel choices for future therapeutic strategies," the authors write.

In an accompanying editorial, James A. DeCaprio, M.D., of the Dana-Farber Cancer Institute in Boston, points out parallels between MCPyV infection in Merkel cell carcinoma and human papillomavirus infection in head and neck cancers, suggesting reasons that the presence of these viruses would predict a better prognosis.

"Perhaps expression of the viral oncogenes can induce or promote the development of cancers that have fewer host cell chromosomal abnormalities, which may result in tumors with simpler genomic abnormalities," the editorialist writes. "Alternatively, the viral oncogenes may specifically perturb host signaling pathways, including immune surveillance, that render them less aggressive or lethal."

Article: Joensuu Heikki,
Editorial: James DeCaprio,

Survivors of Childhood Central Nervous System Cancer Face Persistent Risks as Adults

Long-term survivors of childhood central nervous system (CNS) malignancies remain at risk for death and are at increasing risk for developing subsequent cancers and chronic medical conditions over time, according to a new study published online June 17 in the JNCI.

It was known that survivors of childhood CNS malignancies faced long-term side effects, but this large, 30-year study is one of the first to examine their long-term risks of subsequent cancers and debilitating medical conditions, as well as sociodemographic outcomes into adulthood.

To address these risks, Gregory Armstrong, M.D., M.S.C.E., at St. Jude Children's Research Hospital in Memphis, Tenn., and colleagues collected information on treatment, mortality, chronic medical conditions, and neurocognitive functioning from patients who had been diagnosed between 1970 and 1986 within the Childhood Cancer Survivor Study and had survived for 5 or more years after diagnosis.

The researchers found that these survivors had a risk of death that was 13 times that of the general population. Recurrence or progression of primary disease was the most common cause of death in the first 30 years after diagnosis. The risk of developing a subsequent cancer was associated with radiation exposure during initial treatment, and this risk continues to increase over time in this population. For patients with certain tumor types, increased radiation therapy was also associated with neurocognitive impairment. Radiation of the frontal/temporal lobes was associated with lower levels of employment and marriage.

"Continued follow-up will help determine temporal patterns in incidence and late effects as this cohort ages," the authors write. "Modern therapeutic regimens that increasingly use chemotherapy to reduce [radiation therapy] dose or use limited [radiation therapy] fields will likely improve long-term outcomes and minimize the risk of adverse late effects."

Contact: Summer Freeman,, 901-595-3061

Adding SNPs to Breast Cancer Risk Model Does Not Increase Accuracy Meaningfully

Adding genotypes for seven single-nucleotide polymorphisms (SNPs) to the Breast Cancer Risk Assessment Tool (BCRAT) provided only a small improvement in the accuracy of the tool, according to a new study published online June 17 in the JNCI.

Previous research had recommended a comparison of BCRAT, commonly known as the Gail Model, and BCRATplus7, which includes the seven SNPs associated with breast cancer.

Based on that recommendation, Mitchell H. Gail, of the Division of Cancer Epidemiology and Genetics, National Cancer Institute in Bethesda, Md., investigated four medically important applications that are based on risks and benefits to compare the performance of BCRAT with BCRATplus7. The applications were used to decide which women could benefit from tamoxifen to prevent breast cancer; which should have screening mammography; assessing the extent of reclassification of breast cancer risk; and allocating access to screening mammography under cost constraints.

Gail found that for all applications, the value added with BCRATplus7 compared with BCRAT was very small.

"In view of these uncertainties and the small improvements from BCRATplus7 in these applications, further studies are needed to validate models with SNPs and to assess how much they improve performance over simpler models," the author writes.

Contact: NCI Press Officers,

Risk of Liver Cancer in Women with Hepatitis B Virus Infection Varies with Number of Pregnancies

Risk for hepatocellular carcinoma, a primary malignancy of the liver, was statistically significantly higher among women with hepatitis B virus (HBV) infection than among women without the virus, according to a study published online June 17 in the JNCI.

Because hepatocellular carcinoma mostly occurs in men, few women have been included in long-term studies of the association between HBV infection and this carcinoma.

In this study, Chien-Jen Chen, Sc.D., of the Genomics Research Center in Taipei, Taiwan, and colleagues used a nationwide cohort of more than 1.5 million pregnant Taiwanese women tested from 1983 to 2000 to study relationships of HBV infection and parity with hepatocellular risk.

The researchers found that risk for hepatocellular carcinoma during follow-up was statistically significantly higher among pregnant women who had chronic, active, or persistent HBV infections (and even in those who had seroclearance for hepatitis B surface antigen during follow-up) than among women who were not carriers of hepatitis B surface antigen at study entry.

The more children a woman had, the lower her risk appeared to be. This inverse relationship between parity and the risk of hepatocellular carcinoma was statistically significant. "Underlying biological mechanisms responsible for this...merit further investigation," the authors write.

Contact: Chien-Jen Chen,


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