Other highlights in the June 1 JNCI


Study Examines Cancer Risk in ATM Mutation Carriers

Women who carry one mutated copy of the ATM gene have twice the risk of developing breast cancer during their lifetime and almost five times the risk of developing breast cancer before age 50 compared with the general population, according to a new study.

Mutations in both of the ATM gene are responsible for ataxia telangiectasia (A-T), a rare autosomal recessive neurologic disorder. A-T patients have a higher risk of developing childhood lymphoid leukemias and lymphomas in addition to epithelial tumors later in life. Studies have also indicated that individuals who carry one mutated copy of the ATM gene (i.e., heterozygous mutation carriers) may have a higher risk of breast cancer and perhaps other cancers, but the precise risk is uncertain.

To determine the risk of cancer among heterozygous ATM mutation carriers, Douglas F. Easton, Ph.D., of Cambridge University in England, and colleagues obtained cancer incidence and mortality information for 1,160 relatives of 169 British A-T patients.

Female ATM mutation carriers had twice the risk of breast cancer overall compared with the general population. This is equivalent of a lifetime risk of breast cancer of one in six among mutation carriers compared with one in 11 in the general population of England and Wales. Among women younger than age 50, mutation carriers had five times the risk of breast cancer as the general population.

The estimated risk of cancer before age 80 was only slightly greater among male ATM mutation carriers than in the general male population (39% versus 36%), but this risk was much greater among female ATM mutation carriers than in the general female population (35% versus 21%). There was also some evidence of an increased risk of colorectal cancer and stomach cancer among ATM mutation carriers. Contact: Nick Stewart, Cancer Research UK, (44) 20 7061 8317, [email protected]

Drug May Reduce Recurrence of High-Grade Colorectal Adenomas

A new study has found that ursodeoxycholic acid (UDCA) treatment is associated with a 39% relative reduction in the risk of recurrence of high-grade colorectal adenomas.

Secondary bile acids in stool, particularly deoxycholic acid (DCA), have been implicated in the pathogenesis of colorectal cancer. Preclinical research and early-phase trials have indicated that treatment with UDCA, which suppresses many of the biological pathways turned on by DCA, is associated with a reduced incidence of colorectal neoplasia.

David S. Alberts, M.D., of the Arizona Cancer Center in Tucson, and colleagues conducted a phase III double-blind, placebo-controlled trial of UDCA in 1,285 patients who had undergone removal of a colorectal adenoma. The participants were randomly assigned to received UDCA treatment or a placebo for 3 years or until a follow-up colonoscopy.

UDCA treatment was associated with a 12% reduction in adenoma recurrence compared with placebo (43.9% of the placebo group versus 41.0% of the UDCA group had at least one recurrent adenoma), but this result was not statistically significant. However, UDCA treatment was associated with a statistically significant 39% reduction in the recurrence of adenomas with high-grade dysplasia (8.7% in the placebo group versus 5.5% in the UDCA group). "Because severely dysplastic lesions have a greater potential for progression to invasive colorectal carcinoma than lesions with less dysplasia, this finding warrants further investigation in future chemoprevention trials of UDCA in this population," the authors write.

Contact: Donna Breckenridge, Communications, Arizona Cancer Center, 520-626-2277, [email protected]

Molecule May Be Target for Treatment of Malignant Glioma

A new study has found that a molecule--the formylpeptide receptor (FPR), which is expressed in highly malignant human glioma cells and appears to mediate cell movement and growth and angiogenesis in human glioblastoma--may be a molecular target for the development of treatments for glioma.

Glioma is the most common malignant neoplasm of the central nervous system. Because FPR, which was believed to be mainly involved in proinflammatory and antibacterial responses, was discovered to be expressed by some glioma cells, Ji Ming Wang, M.D., Ph.D., of the National Cancer Institute, and colleagues investigated the relationship between FPR and the biologic behavior of glioma cells.

They found that highly malignant human glioblastoma cell lines, grade IV glioblastoma multiforme, and grade III anaplastic astrocytomas express FPR. Inhibiting FPR with its short interfering RNA substantially reduced tumorigenicity of glioblastoma cells injected into nude mice. The authors conclude that FPR may mediate cell movement and growth and angiogenesis of malignant human gliomas.

Contact: National Cancer Institute Press Office, 301-496-6641, [email protected]

Lack of NM23 Gene Expression Contributes to Metastasis in Mouse Model of Cancer

Lack of expression of the mouse equivalent of the human gene NM23 promotes metastasis in a mouse model of liver cancer, according to a new study.

The NM23 gene is thought to suppress the metastatic spread of solid tumors. Marie-Lise Lacombe, Ph.D., of INSERM in Paris, and colleagues used transgenic mice that lacked the mouse NM23-M1 gene (the mouse equivalent of NM23) in two mouse models of liver cancer to examine the role of NM23 in hepatic tumor development and metastatic dissemination.

They found that in both models, the NM23 protein was overexpressed in the primary liver tumors of mice that had the NM23-M1 gene compared with non-tumor liver tissue. However, the lack of the NM23-M1 gene had no effect on the primary tumor in either model. In the model that developed pulmonary metastases, more mice that lacked the NM23-M1 gene developed metastases than mice that expressed the gene. The authors conclude that a lack of NM23-M1 expression promotes metastasis in this animal model of liver carcinogenesis.

Contact: INSERM Press Office, 33-1-44 23 60 98, [email protected]

Also in the June 1 JNCI:

  • Shorter Course of Radiotherapy Effective for Palliation of Painful Bone Metastases: http://www.eurekalert.org/emb_releases/2005-05/jotn-sco052505.php
  • Cancer Patients Have Increased Risk of Cognitive Dysfunction, Study Finds: http://www.eurekalert.org/emb_releases/2005-05/jotn-cph052505.php
  • Study Examines NSAID Use and Breast Cancer Risk: http://www.eurekalert.org/emb_releases/2005-05/jotn-sen052505.php

    Source: Eurekalert & others

    Last reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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