Other highlights of the March 17 issue of JNCI

Infection with a high-risk type of human papillomavirus (HPV) in oral epithelial cells may be an independent risk factor for head and neck cancer, according to a new study.

HPV has been associated with the development of head and neck cancers. Elaine M. Smith, Ph.D., of the University of Iowa, and colleagues conducted a case–control study to determine the risk factors for head and neck cancer in relation to HPV infection. The authors detected high-risk HPV types in oral cells from 22.9% of the 201 case patients and 10.8% of the 333 control subjects. Individuals with high-risk HPV types, but not individuals with nononcogenic or low-risk HPV types, had an increased risk of head and neck cancer compared with HPV-negative individuals.

High-risk HPV types detected in oral exfoliated cells were predictive of high-risk HPV types in tumor tissue. The authors found a synergistic effect between detection of high-risk HPV and heavy alcohol consumption, but only an additive effect between detection of high-risk HPV and tobacco use. The authors conclude that HPV testing using an oral rinse may provide an early biomarker for HPV-associated head and neck cancer.

Contact: Dan McMillan, University of Iowa, 319-335-6835, daniel-mcmillan@uiowa.edu

Letrozole Extends Time to Tumor Progression in Mouse Model

In a mouse model of human breast cancer, the drug letrozole more effectively extends time to tumor progression than tamoxifen or various combinations and dosing schedules of tamoxifen plus letrozole.

Clinical data from patients with estrogen receptor-positive breast cancer suggest that aromatase inhibitors, such as letrozole, are more effective and better tolerated than the antiestrogen tamoxifen. To investigate ways to optimize treatment using letrozole and tamoxifen, Brian J. Long and Angela M. Brodie, Ph.D., of the University of Maryland School of Medicine, Baltimore, and colleagues treated a mouse xenograft breast cancer model with various combinations of these drugs.

First-line treatment with letrozole was superior, in terms of time to tumor progression, to that with tamoxifen or with tamoxifen plus letrozole. Treatment with alternating courses of the two drugs was also not as effective as treatment with letrozole alone. Tumors progressing on tamoxifen were sensitive to second-line therapy with letrozole, but tumors progressing on letrozole were not sensitive to second-line therapy with tamoxifen or with fulvestrant, another antiestrogen. The authors note that further studies will be needed to determine the most effective second-line therapies for tumors that progress on letrozole.

Contact: Larry Roberts, University of Maryland, 410-706-7590, LRoberts@som.umaryland.edu

Also in the March 17 JNCI:

• Arsenic Exposure and Estrogen Signaling: Exposure of pregnant mice to arsenic results in the development of a range of tumor types--including hepatocellular carcinoma (HCC)--in their adult offspring that are similar to those induced in adult mice by exposure to estrogenic compounds. A new study suggests that arsenic exposure alters estrogen signaling, which may in turn be associated with the development of HCC. Specifically, the authors found that adult mice that had been exposed to arsenic in utero overexpressed estrogen receptor-alpha in their livers. "Thus, the accumulated results from the present study suggest that overexpression of [estrogen receptor-alpha] is an important molecular event in arsenic carcinogenesis, at least in the liver." The study was conducted by Michael P. Waalkes, Ph.D., of the National Cancer Institute at the National Institute of Environmental Health Sciences, Research Triangle Park, N.C.

• Melatonin and Breast Cancer: Experiments in animals have suggested that melatonin, a pineal hormone, has a protective role in the development of breast cancer, but results from several human studies have been inconsistent. Ruth C. Travis, M.Sc., of Cancer Research U.K., and colleagues compared levels of a metabolite of melatonin in the urine of 127 patients diagnosed with breast cancer with those of 353 control women to determine whether low levels of melatonin were associated with an increased risk for developing breast cancer. They found no evidence that the level of melatonin is associated with the risk for breast cancer. However, they note that other prospective studies are needed to further explore the relationship.

• Assessing the Probability That a Positive Report is False: In a commentary, Sholom Wacholder, Ph.D., of the National Cancer Institute, and colleagues examine the statistical methods used in reports of associations between genetic variants and common cancers. They argue that the practice of using the P value alone to declare a finding to be statistically significant is no longer appropriate for deciding which of the many reports of associations between genetic variants and common cancer sites are truly significant. They propose, instead, that investigators use another test--one that determines the probability of no true association between a genetic variant and a disease, given a statistically significant association--to evaluate whether a finding is noteworthy. The authors conclude that this alternative approach, the false positive report probability, helps formalize what investigators have always been performing informally that is, tempering enthusiasm for surprising findings with consideration of plausibility.

• Hypermethylation and transcriptional downregulation of the carboxyl-terminal modulator protein gene in glioblastomas, Christiane B. Knobbe, et al., Heinrich-Heine-University, Dusseldorf, Germany.

• Trends in the Treatment of Ductal Carcinoma In Situ of the Breast, Nancy Baxter, et al., University of Minnesota, complete press release available at: http://www.eurekalert.org/emb_releases/2004-03/jotn-tod031104.php

Note: The Journal of the National Cancer Institute is published by Oxford University Press and is not affiliated with the National Cancer Institute. Attribution to the Journal of the National Cancer Institute is requested in all news coverage. Visit the Journal online at http://jncicancerspectrum.oupjournals.org/.