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Other highlights in the August 3 JNCI

Journal of the National Cancer Institute

Other highlights in the August 3 JNCI include a study that finds body size associated with the risk of myeloid leukemia, the identification of a potential colon cancer biomarker, an evaluation of the revised American Joint Committee on Cancer (AJCC) tumor-node-metastasis staging system and its use after neoadjuvant chemotherapy for breast cancer, and a study of how imiquimod (Aldara) works against skin cancer.

Body Size Associated With Increased Risk of Myeloid Leukemia

A new study has found that greater body size--including higher body mass index, fat-free mass, and waist circumference--was associated with an increased risk of myeloid leukemia.

To determine if body size and composition was associated with risk of lymphohematopoietic malignancies (cancers of the blood and lymph systems), Graham G. Giles, Ph.D., of the Cancer Council Victoria in Melbourne, Australia, and colleagues followed 40,909 people aged 27 to 75 for an average of 8.4 years. They measured waist and hip circumference, height, and weight, calculated the waist-to-hip ratio and the body mass index, and measured the fat mass and fat-free mass of each participant. They also gathered information about malignancies from the population cancer registry.

The authors found that risk of myeloid leukemia was positively associated with body mass index, fat-free mass, and waist circumference, whereas risks of multiple myeloma, lymphocytic leukemia, hairy cell leukemia, Hodgkin lymphoma, and non-Hodgkin lymphoma were not associated with body size or composition.

Contact: Zoe Furman, Cancer Council Victoria, 61-3-9635-5517,

Study Identifies Potential Colon Cancer Biomarker

A new study has found that specific modifications of the vimentin gene can be detected in fecal DNA of some people with colon cancer and may have use as a biomarker of the disease.

Surgical cure rates for colon cancer are high when the cancer is detected in an early stage. Although there are several methods available for colon cancer detection, researchers have been searching for better methods, such as biomarkers. In cancer cells, the transcription of tumor suppressor genes is often silenced by increased or aberrant DNA methylation, and aberrantly methylated DNA has been proposed as a potential tumor biomarker.

To determine whether methylation of the vimentin gene could be a possible biomarker for colon cancer, Sanford D. Markowitz, M.D., Ph.D., of Case Western Reserve University and the Ireland Cancer Center of University Hospitals in Cleveland, and colleagues at Case and at Exact Sciences in Marlborough, Mass., compared methylation of the gene in cancer tissues and fecal DNA from colon cancer patients versus control samples from healthy subjects.

Aberrant vimentin methylation was detected in 83% and 53% of tumors from two independent groups of colon cancer patients, respectively, and in 46% of fecal DNA from a third set of colon cancer patients, with 43% sensitivity (proportion of true-positive results) for detecting stage I and II cancers. The specificity (proportion of true-negative results) of the test with fecal DNA was 90%. The authors now plan to use their assay in prospective studies designed to determine optimal biomarkers for colon cancer detection.

In an editorial, Dean E. Brenner, M.D., of the University of Michigan Cancer Center in Ann Arbor, and Gad Rennert, M.D., Ph.D., of the Clalit Health Service National Israeli Cancer Control Center in Haifa, emphasize need to create more sensitive non-invasive colorectal cancer screening methods that are cost-effective and can detect adenomas. They also discuss potential technical problems of fecal-based DNA testing.


  • Article: Goerge Stamatis, Case Western Reserve University, 216-368-3635,
  • Editorial: Nicole Fawcett, University of Michigan Comprehensive Cancer Center, 734-764-2220,

    Stage of Tumor After Neoadjuvant Chemotherapy for Breast Cancer Associated With Survival, Study Finds

    The stage of the tumor left after neoadjuvant chemotherapy for breast cancer--as determined by the revised American Joint Committee on Cancer (AJCC) tumor-node-metastasis staging system--is associated with both distant disease-free survival and overall survival, according to a new study.

    In breast cancer, the extent of tumor left behind after neoadjuvant chemotherapy is an established intermediate endpoint for relapse and survival. In January 2003, the AJCC modified their tumor-node-metastasis staging system. To determine whether this new system is able to predict patient survival after neoadjuvant chemotherapy for breast cancer, Lisa A. Carey, M.D., of the University of North Carolina at Chapel Hill, and colleagues assessed the stage of the residual tumor in 132 patients with nonmetastatic breast cancer after they had undergone neoadjuvant chemotherapy. The patients were then followed for a median of 5 years.

    The authors found that the pathologic stage of residual tumor was strongly associated with both distant disease-free survival and overall survival. They conclude that classification of residual tumor in the breast after neoadjuvant chemotherapy using the revised AJCC tumor-node-metastasis system is useful for predicting distant relapse and survival.

    Contact: Dianne Shaw, Communications, UNC Lineberger Comprehensive Cancer Center, 919-966-5905,

    Study Elucidates How Skin Cancer Treatment Works

    A new study has found that a type of immune system cell found in blood and lymphoid organs called plasmacytoid predendritic cells (PDCs) may play a role in response to imiquimod (Aldara), a drug used topically to treat some types of skin cancer.

    Imiquimod induces production of proinflammatory cytokines that stimulates an antitumor immune response, but the nature of this immune response had not been elucidated. Mirjana Urosevic, M.D., of the University Hospital Zurich in Switzerland, and colleagues studied gene expression profiles from skin cancer patients treated with imiquimod. They found that imiquimod induced gene expression patterns that were associated with the number of PDCs recruited to the treatment site and that the strength of the imiquimod-induced immune response was directly associated with the number of PDCs recruited to the tumor. They concluded that PDCs appear to have a role in the responsiveness of lesions to imiquimod treatment.

    Contact: Mirjana Urosevic ( or Reinhard Dummer (, University Hospital Zurich

    Also in the August 3 JNCI:

  • Study Evaluates Averted Costs of Neuroblastoma Screening
  • Few Benefits, Many Costs Associated With Changing Definition of "Abnormal" PSA Level


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