Also in the July 8 JNCI

Reductions in Iron Blood Levels Associated with Decreased Cancer Risk in Men with Peripheral Arterial Disease

Men with peripheral arterial disease who participated in a randomized controlled trial in which their iron stores were reduced by blood drawing had a reduced incidence of cancer relative to men in the trial who did not undergo blood letting.

Observational studies have suggested that lower levels of iron in the blood may be associated with a reduced risk of cancer. Data from animal studies are consistent with the observation, and researchers hypothesize that iron catalyzes the production of free radicals that damage cellular components, including DNA.

The current randomized controlled trial enrolled individuals with peripheral arterial disease from Veterans Administration facilities. The primary goal of the trial was to examine the effect of reducing of iron stores on the development of vascular disease. In the current analysis, Leo Zacharski, M.D., of the Department of Veterans Affairs Medical Center in White River Junction, Vt., and colleagues compared the rate of new visceral malignancies and cause-specific mortality in the trial participants, 98.8 percent of whom were men. The malignancy and mortality data were collected prospectively.

The 636 participants who underwent phlebotomy were 37 percent less likely to develop cancer during the 4.5-year follow-up period than were the 641 participants assigned to the control arm (38 versus 60 cancers). Individuals in the experimental arm also had a lower cancer-specific and all cause-mortality compared with individuals in the control arm.

"Findings from this study support the hypothesis that ambient levels of body iron stores represented by the serum ferritin level are associated with cancer risk and that lowering iron levels reduces cancer risk," the authors write.

In an accompanying editorial, Gustaf Edgren, Ph.D., Olof Nyrén, M.D., Ph.D., and Mads Melbye, M.D., Ph.D., of the Karolinska Institute in Stockholm and Statens Serum Institut in Copenhagen commend the study authors for their innovative and well-executed trial. The editorialists caution, however, that the trial was not designed to investigate cancer incidence and the current report is based on an ad hoc analysis. "The results are so unexpected that all possibilities for bias must be carefully examined," the editorialists write, particularly because of the timing and magnitude of the effect. "For the present, the results have to be interpreted with caution."

Contact:

• Article: Ken Thibodeaux, (802) 295-9363, extension 5424
• Editorial: Mads Melbye, mme@ssi.dk, +45-32683163

Cancer Patients Less Likely to Disenroll from Medicare Managed Care Plans Than Cancer-Free Peers

Medicare participants with a cancer diagnosis are less likely to switch from a managed care plan to traditional fee-for-service Medicare than matched subjects who do not have a cancer diagnosis.

In many locations, Medicare beneficiaries can choose between traditional fee-for-service insurance and managed care plans. Managed care plan participants incur fewer out-of-pocket costs than those enrolled in traditional Medicare but may be restricted in their access to particular healthcare providers.

To determine whether Medicare participants are likely to disenroll from managed care plans following a cancer diagnosis, Elena Elkin, Ph.D., of Memorial Sloan-Kettering Cancer Center in New York and colleagues used the Surveillance, Epidemiology, and End Results (SEER) database and linked Medicare enrollment files. The researchers identified 28,331 women with breast cancer, 26,494 individuals with colorectal cancer, 29,046 men with prostate cancer, and 31,243 individuals with lung cancer who were diagnosed between 1995 and 2002. The researchers compared the frequency of voluntary disenrollment during the two years after diagnosis with enrollment changes by matched control subjects who did not have a cancer diagnosis.

Cancer patients were statistically significantly less likely to disenroll from a Medicare managed care plan than individuals who were cancer-free. The results were consistent across age, disease site and stage, race, and location in the United States.

"If voluntary disenrollment from Medicare managed care is, in fact, beneficiaries' way of 'voting with their feet,' then our results suggest that enrollees facing a serious, potentially life-threatening illness are as satisfied with Medicare managed care, if not more so, than their cancer-free peers," the authors write.

Contact: Jeanne D'Agostino, dagostij@mskcc.org, (646) 227-3573

Cyclin A1 Expression Promotes Prostate Cancer Invasion and Metastases

Cyclin A1 promotes prostate cancer invasion and metastasis by increasing the expression of key signaling proteins and extracellular proteins.

Cyclin A1 is a cell cycle regulatory protein and is thought to play a role in a variety of cancers. Recently, Jenny Liao Persson, Ph.D., of the Lund University Hospital in Malmö, Sweden, and colleagues found that it was highly expressed in prostate tumor samples and was associated with aggressive tumor histology and expression of vascular endothelial growth factor (VEGF), one of the key factors in angiogenesis.

In the current study, Persson's team examined expression of cyclin A1, VEGF, metalloproteinases (MMPs) in primary malignant tumors, and adjacent benign prostatic tissues from 482 patients with prostate cancers of various stages. The team further tested the impact of increased cyclin A1 expression in tumor invasion and metastasis in a mouse model of prostate cancer.

The researchers found that prostate cancer cells engineered to overexpress cyclin A1 caused lung and liver metastases, while cells that did not overexpress cyclin A1 did not cause lung and liver metastases. The team also found that cyclin A1 works with the androgen receptor to directly increase expression of VEGF and a MMP, which has previously been found to influence cancer cell invasiveness.

"The finding that cyclin A1 regulates the expression of a growth factor signaling molecule (VEGF) and extracellular proteases (MMPs) and promotes tumor cell invasion and metastasis in part through MMPs and [urokinase-type plasminogen activator] suggests that cyclin A1 may be a key regulator of tumor invasion and metastasis," the authors write.

Contact: Jenny Persson, jenny_l.persson@med.lu.se, +46-40338391

Also in the July 8 JNCI:

• http://www.eurekalert.org/emb_releases/2008-07/jotn-spd070308.php
• http://www.eurekalert.org/emb_releases/2008-07/jotn-aoe070308.php
• http://www.eurekalert.org/emb_releases/2008-07/jotn-hea070308.php

Note to Reporters:

We have started up an e-mail list to alert reporters when papers are available on the EurekAlert site. If you would be interested on being on this list, please let us know at jncimedia@oxfordjournals.org. The content will continue to be available through EurekAlert's e-mail system and our EurekAlert page.

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://jnci.oxfordjournals.org/.