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Transcript for Summary of Issue 22

Hi and welcome to the JNCI podcast. I’m Steve Graff, JNCI’s assistant news and media editor, and I’ll be taking you through the next issue of the Journal of the National Cancer Institute.

Issue 22 includes a study and editorial that looked at emerging patterns in smoking and bladder cancer. Also: researchers from Italy found that people living in volcanic areas may be a greater risk for thyroid cancer. Another study in this issue found that the small-molecule inhibitor nutlin-3 may be a viable treatment option for children with neuroblastoma with wild-type p53 activity. One study looked at recent changes in breast cancer incidence in Spain. In this issue’s commentary, a researcher argues that a relative utility curve is a simple method to evaluate risk prediction in a medical decision-making framework.

More on these studies coming up next.

A study published online November 16 found that risk of bladder cancer for smokers has increased since the mid-1990s, with a risk progressively increasing to a level five times higher among current smokers in New Hampshire than that among nonsmokers in 2001-2004.

Dalsu Baris, of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, in Bethesda, Md., and her colleagues from NCI, Dartmouth Medical School, and the departments of health for the states of Maine, New Hampshire and Vermont, examined bladder cancer risk in relation to smoking practices based on data from a large, population-based case–control study conducted in Maine, New Hampshire, and Vermont from 2001 to 2004. To examine changes in smoking-induced bladder cancer risk over time, the researchers compared odds ratios for New Hampshire residents in this study with those from two, case–control studies.

Among New Hampshire residents, there was a statistically significant, progressive increase in bladder cancer risk among both former and current smokers compared with nonsmokers over each time period. According to the authors, this may be partly attributable to changes over time in the concentration of bladder carcinogens in cigarette smoke, as well as the introduction and increased popularity of low-tar/low-nicotine cigarettes.

In an accompanying editorial, Anthony J. Alberg, of the Medical University of South Carolina in Charleston, and James R. Hebert, of the Department of Epidemiology and Biostatistics at the University of South Carolina in Columbia, note that given the substantial body of evidence linking bladder cancer and smoking, the most important aspect of this finding was that the association has substantially increased from 1994 to 2004. The editorialists agree that the data suggest that an increase in the carcinogenic content of cigarettes over time could be partly responsible.

People living in volcanic areas may be at a higher risk for thyroid cancer, according to a study published online November 5.

The increasing incidence of thyroid cancer has been attributed to more sensitive screening, but recent evidence indicates that this may not be the only cause.

To study this, Gabriella Pellegriti, of the endocrinology division, University of Catania Medical School, in Italy, and colleagues collected incidence of thyroid cancers in Sicily from January 1, 2002 through December 31, 2004 to compare the cancer rates of residents living in the volcanic area of Mt. Etna of Catania with those in the rest of Sicily.

The researchers found that residents of the Catania province had a more than two times higher incidence of papillary thyroid cancer than elsewhere on the island. Also, papillary tumors from patients in Catania more frequently carried the BRAF V600E gene mutation, which has been associated with more aggressive thyroid cancer.

The authors point out that a volcanic environment—which can produce toxic compounds and elements that may pollute the water—may increase the incidence of thyroid cancer; however, the mechanism by which it affects risk is unknown.

The small-molecule inhibitor nutlin-3 may be a viable treatment option for neuroblastoma patients with wild-type p53 activity, according to a new study published online November 10.

In this study in mice, Tom Van Maerken, , Center for Medical Genetics, Ghent University Hospital in Belgium, and colleagues evaluated the antitumor efficacy of nutlin-3, a potent and selective antagonist of the p53–MDM2 interaction.

Researchers found that nutlin-3 activates the p53 pathway and suppresses tumor growth in the mice models of chemoresistant neuroblastoma, provided that wild-type p53 is present. (Neuroblastoma is a childhood tumor that often has a poor outcome). Oral administration of nutlin-3 as a single agent reduced tumor growth and metastasis.

In an accompanying editorial, Eugene Kim, and Jason Shohet, of the Baylor College of Medicine in Houston, review the role of MDM2 and ARF in suppressing p53 during neuroblastoma pathogenesis and the sensitivity of this tumor to MDM2 inhibition. They suggest that the next step is to test agents that “re-activate” p53 in high-risk neuroblastoma by inhibiting MDM2 in human trials.

After a steady increase of invasive breast cancer cases in Spanish women during the 1980s and 1990s, incidence rates abruptly declined starting in 2001—a trend most likely explained by a period effect linked to screening saturation, according to this study published online October 26.

Marina Pollán, of the Centro Nacional de Epidemiología, Instituto de Salud Carlos III in Madrid, and colleagues identified invasive breast cancer cases from population-based cancer registries in Spain that had at least 10 years of uninterrupted registration over the period 1980–2004. The researchers took into account the starting year of the corresponding breast cancer screening program for the population and the year in which the screening program achieved full coverage of the target population.

Overall incidence rates rose by 2.9% annually during the 1980s and 1990s, but there was a statistically significant change in this trend in 2001, when incidence declined annually by 3.0%. There was a steady increase in incidence for women younger than 45 years, an abrupt downturn in 2001 for women aged 45–64 years, and a gradual leveling off in 1995 for women aged 65 years or older.

The sharp decline could be a result of the introduction of screening programs, according to the authors. When screening programs are introduced, cancer incidence can rise because diagnoses occur earlier than they would have without screening. But this rise is temporary.

In commentary published online October 20, Stuart G. Baker, of the National Cancer Institute in Bethesda, Md., said that a relative utility curve is a simple method to evaluate risk prediction in a medical decision-making framework.

Risk prediction models that are based on medical history or the results of tests are becoming common in the cancer literature and are used to provide additional information to those who are involved in making treatment decisions on the basis of estimated risk.

In the commentary, Baker elaborates on the relative utility curve as a method for evaluating risk prediction. He illustrates the application of relative utility curves in an analysis of previously published data involving the addition of breast density to a risk prediction model for invasive breast cancer.

That’s it for this edition of the JNCI podcast.

As always, find these studies online at . Also check out this month’s JNCI interview with Dr. Gadi Rennert, who discussed the recent JNCI article that found Jewish survivors of World War II who were potentially exposed to the Holocaust are at a higher risk for cancer occurrence.

I’m Steve Graff and thanks for listening