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Also in the April 7 JNCI

Subsequent Malignancy a Major Cause of Death in Long-Term Survivors of Hereditary Retinoblastoma

Long-term survivors of hereditary retinoblastoma are at an increased risk of death due to a second cancer, according to a large cohort study.

Retinoblastoma is a very rare cancer of the eye that affects approximately 300 children in the U.S. each year. Survivors of retinoblastoma are at risk of subsequent malignancies but information on the risk of death due to these subsequent cancers is limited among long-term survivors.

In the current study, Chu-Ling Yu, Sc.D., of the National Cancer Institute in Rockville, Md., and colleagues examined the cause of death in a cohort of 1,092 survivors of hereditary retinoblastoma and in 762 survivors of nonhereditary retinoblastoma who were diagnosed between 1914 and 1996.

The mortality rate due to cancers was 35-fold higher in the hereditary retinoblastoma survivors and 2.5-fold higher in the survivors of nonhereditary retinoblastoma, compared with the general population. A total of 151 hereditary retinoblastoma survivors died due to a subsequent cancer, as did 12 survivors of nonhereditary retinoblastoma. Hereditary retinoblastoma survivors were at particular risk of death due to sarcoma, melanoma, and cancers of the brain and nervous system; the risk extended more than 40 years after their initial diagnosis.

"The temporal patterns of site-specific excess risks of subsequent malignant neoplasms in retinoblastoma survivors should inform screening programs designed for the early detection and treatment of subsequent malignant neoplasms," the authors write. Contact NCI press office,, 301-496-6641

Disruption of Cytokine Signaling Promotes Gastric Cancer Growth in Mouse Models

Disruption of transforming growth factor- (TGF-) signaling in gastric cancer cells promotes tumor growth in mouse models.

TGF- is a cytokine that promotes cell proliferation in a variety of tissues and its expression has been associated with progression of diffuse-type gastric cancer. The role of TGF- in gastric cancer is controversial, however.

In the current study, Kohei Miyazono, M.D., of the University of Tokyo and colleagues disrupted TGF- signaling by introducing a dominant-negative TGF- receptor into gastric cancer cell lines. They then investigated proliferation of these cells in culture and tumor growth and angiogenesis in mice injected with these cells.

Expression of the dominant-negative receptor did not increase cancer cell proliferation in vitro but increased tumor growth when the cells were injected into mice. Treatment of tumor-bearing mice with antiangiogenesis compounds slowed tumor growth, suggesting that TGF- signaling accelerated tumor growth by stimulating blood vessel development.

"In conclusion, we have shown that disruption of TGF- signaling in a mouse model of diffuse-type gastric carcinoma, which may be analogous to what occurs during progression of this disease in humans, promotes tumorigenesis by accelerating angiogenesis," the authors write. Based on these data, they hypothesize that angiogenesis inhibitors may be useful treatments for those cancers with disrupted TGF- signaling pathways. Contact Kohei Miyazono, email: or, +03-5841-3345

Perfluorinated Chemicals Not Associated with Cancer in General Population

Perfluorooctanoate and perfluorooctanesulfonate plasma concentrations are not associated with the risk of prostate, bladder, pancreatic, or liver cancer.

The two chemicals, commonly used in manufacturing, are widely found in the environment. Previous studies show that they are found in the blood of both occupationally exposed individuals and the general public. High concentrations of the chemicals have been associated with cancer in animals, but their association with cancer in humans is unknown.

To investigate whether exposure the the two chemicals increases the risk of certain cancers, Kirsten T. Eriksen of the Danish Cancer Society in Copenhagen, and colleagues used a large prospective cohort of Danish-born individuals who were cancer-free when they were enrolled in the study between 1993 and 1997. Within this cohort, the researchers identified 713 participants who were later diagnosed with prostate cancer, 332 with bladder cancer, 128 with pancreatic cancer, and 67 with liver cancer, and they also randomly selected 772 control participants without cancer. They divided the participants into four groups on the basis of their perfluorooctanoate and perfluorooctanesulfonate plasma levels.

There was no association between the plasma concentration of perfluorooctanoate or perfluorooctanesulfonate and risk of prostate, bladder, pancreatic, or liver cancer.

"Additional research is warranted to investigate this relationship further in other cohorts, because this is, to our knowledge, the first study on perfluorinated chemicals and risk for cancer in a general population.," the authors write. Contact Ole Raaschou-Nielsen,, +0045 3525 7617

Meeting Participants Call for Integrated Research on COPD and Lung Cancer Participants at a meeting on chronic obstructive pulmonary disease (COPD) and lung cancer called for integrated research into the two diseases, according to a commentary by Antonello Punturieri, M.D., Ph.D., of the National Heart, Lung, and Blood Institute (NHLBI) and colleagues.

Individuals with chronic obstructive pulmonary disease (COPD) are at increased risk of lung cancer, and smoking is a risk factor for both diseases. However, only a fraction of smokers develop either disease, suggesting that there are genetic factors involved as well.

To better understand how COPD and lung cancer are related and begin to identify opportunities for chemoprevention, the National Cancer Institute and the NHLBI recently co-sponsored a workshop. Meeting participants identified four key research aims:

  • clarify common epidemiological characteristics of lung cancer and COPD,
  • identify shared genetic risk factors,
  • identify and validate biomarkers and gene expression patterns associated with each disease, and
  • determine shared disease mechanisms.

Additionally, to strengthen research interactions, the participants recommended that future longitudinal studies of lung cancer or COPD incorporate baseline and outcome measures for both diseases and that collaborations between the National Cancer Institute and the NHLBI be expanded. Contact NHLBI Communications Office,, (301) 496-4236


Contact: Caroline McNeil
Journal of the National Cancer Institute

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