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Other highlights in the November 17 JNCI

Journal of the National Cancer Institute

Higher Levels of Selenium in Blood Associated With Decreased Risk of Colorectal Cancer

A new study finds that higher levels of selenium in the blood may be associated with a decreased risk of colorectal cancer.

Selenium is a trace element found in meats and grains, but dietary intake can vary by geographic area because of different concentrations of the element in the soil. People living in regions where selenium intake is low have higher rates of several cancers, including colorectal cancer. In addition, secondary analyses of data from a large randomized clinical trial suggested that selenium intake reduces the risk of colorectal cancer, but epidemiologic data has not found a consistent association.

Elizabeth T. Jacobs, Ph.D., of the Arizona Cancer Center in Tucson, and colleagues pooled data from three randomized trials--the Wheat Bran Fiber Trial, the Polyp Prevention Trial, and the Polyp Prevention Study--to assess the effect of selenium levels in the blood on colorectal adenoma recurrence.

Trial participants who were in the highest quartile for blood selenium levels had a 34% decreased risk of developing a new adenoma compared with participants in the lowest quartile. The researchers conclude that these results support previous findings that higher levels of selenium in the blood may be associated with a decreased risk of colorectal cancer.

In an editorial, Scott M. Lippman, M.D., of the University of Texas M. D. Anderson Cancer Center in Houston, and colleagues discuss possible biologic mechanisms for this association, including selenium's effects on gene promoter methylation and polyunsaturated fatty acid metabolism.


  • Article: Donna Breckenridge, Arizona Cancer Center, 520-626-2277,
  • Editorial: Laura Sussman, M. D. Anderson Cancer Center, 713-745-2457,

    Study Examines Long-Term Effects of Neoadjuvant Chemotherapy for Head and Neck Cancer

    The addition of neoadjuvant chemotherapy to concurrent chemoradiation may be a promising approach for treating patients with inoperable advanced head and neck cancer, according the authors of a 10-year follow-up of a randomized trial.

    In 1986, a randomized phase III trial began in which 237 patients with nonmetastatic stage III or IV head and neck squamous cell carcinoma were treated with either four cycles of neoadjuvant chemotherapy followed by locoregional treatment (surgery and radiotherapy or radiotherapy alone) or locoregional treatment alone. Two years after treatment began, there was no difference in survival between the two groups.

    In a follow-up at 5 and 10 years after treatment, Adriano Paccagnella, M.D., of SS Giovanni and Paolo Hospital in Venice, and colleagues report again that there was no difference in survival between the two groups. However, among patients who did not receive surgery because their tumors were inoperable, those who received neoadjuvant chemotherapy had a higher rate of survival than patients who did not receive chemotherapy.

    In an editorial, Arlene A. Forastiere, M.D., of the Johns Hopkins Kimmel Cancer Center in Baltimore, notes that these promising follow-up results bolster soon-to-be activated trials of chemoradiotherapy--the current standard of treatment for advanced head and neck cancer--with and without neoadjuvant chemotherapy.


  • Article: Laura McMahon, Ospedale Umberto I, 0039-041-2608339,
  • Editorial: Vanessa Wasta, Johns Hopkins Kimmel Cancer Center, 410-614-2916,

    Trial Compares Docetaxel to Paclitaxel for First-Line Treatment of Ovarian Cancer

    The combination of docetaxel and carboplatin for first-line treatment of ovarian cancer appears to result in similar rates of survival compared with the current standard, paclitaxel and carboplatin--although the toxicities of the drugs are different--according to a new study.

    Chemotherapy with a platinum agent and the taxane paclitaxel is considered the standard of care for treatment of ovarian cancer. However, another taxane, docetaxel, has shown superiority over paclitaxel in the treatment of metastatic breast cancer. In addition, studies have shown that the combination of docetaxel and carboplatin is a feasible treatment for ovarian cancer.

    To compare docetaxel-carboplatin and paclitaxel-carboplatin for the treatment of ovarian cancer, Paul A. Vasey, M.D., of the Royal Brisbane and Women's Hospital in Herston, Australia, and the Scottish Gynaecological Cancer Trials Group randomly assigned 1,077 patients with ovarian or primary peritoneal cancer to receive either treatment. Both groups had similar rates of progression-free survival and response. In the group treated with docetaxel-carboplatin, there was less neurotoxicity, higher rates of neutropenia, and improvement in many quality-of-life parameters. The researchers conclude that docetaxel-carboplatin should be viewed as an alternative to treatment with paclitaxel-carboplatin for women newly diagnosed with ovarian cancer.

    Contact: Margaret Cochran, Media and Communications, Royal Brisbane and Women's Hospital, 04-1255-7831,

    Arthritis Treatment May Reactivate Virus Responsible for Some Lymphomas

    Methotrexate, a treatment for rheumatoid arthritis and polymyositis, may promote the development of Epstein-Barr virus (EBV)-positive lymphomas in patients with autoimmune diseases by reactivating latent EBV and by the drug's immunosuppressive properties, according to a new study.

    EBV is a human herpesvirus that is found in more than 90% of the adult population. The virus establishes a lifelong persistent infection of B cells and is associated with a variety of B-cell disorders, including mononucleosis and Hodgkin lymphoma. EBV-positive lymphomas occur more frequently in rheumatoid arthritis and polymyositis patients taking the drug methotrexate than in patients treated with other equally immunosuppressive drugs.

    By studying the effect of methotrexate on EBV-infected cell lines, Shannon Kenney, M.D. of the Lineberger Comprehensive Cancer Center at the University of North Carolina Chapel Hill, and colleagues demonstrate that methotrexate induces reactivation of EBV from latent infection, leading to the release of infectious virions. The researchers also found that rheumatoid arthritis and polymyositis patients treated with methotrexate had higher EBV loads than patients treated with other immunosuppressive regimens. They conclude that the combination of methotrexate's ability to induce EBV replication in such patients while promoting immunosuppression might explain the association of the drug with EBV-positive lymphomas.

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

    Heartburn Medication May Reduce Tumor Resistance to Cytotoxic Drugs

    Proton pump inhibitors--a type of heartburn medication--may be able to reverse tumor resistance to cytotoxic drugs such as cisplatin or 5-fluorouracil, according to a new study.

    Some solid tumors may be resistant to cytotoxic drugs because the pH outside the tumor cells is more acidic than that of normal tissues, impairing the ability of the cells to take up these drugs. Proton pump inhibitors, a class of drugs that includes omeprezole (Prilosec) and esomeprazole (Nexium), can increase the extracellular pH, which might reverse the inability of tumor cells to take up cytotoxic drugs.

    In a study of tumor cell lines and an animal tumor model, Stefano Fais, M.D., Ph.D., of the Instituto Superiore di Sanitá in Rome, and colleagues show that pretreatment with proton pump inhibitors caused tumor cells resistant to cisplatin to become sensitive to the anticancer drugs. They suggest that this strategy may be useful for treating human solid tumors that are drug resistant or even for increasing the efficacy of antitumor drugs in drug-sensitive tumors.

    Contact: Mirella Taranto, Press Office, Instituto Superiore di Sanitá, 39-06-4990-2264-2950,

    Altered Protein Expression May Reduce p53 Activity in Lung Tumors

    The tumor suppressor protein p53 is a key regular of the cell cycle, and the p53 gene is the most frequent genetic defect in human tumors. The protein Pirh2 was recently discovered to negatively regulate p53 by targeting the protein for degradation.

    In a new study of human and mouse lung tumors, Miguel A. Villalona-Calero, M.D., of Ohio State University in Columbus, and colleagues found that Pirh2 protein expression was higher in most of the lung tumors compared with normal lung tissue. In addition, in the mouse tumors, p53 was more ubiquinated--marked for degradation or destruction--compared with normal tissue, and overall p53 expression was lower in the tumors than in normal tissue. The authors conclude that increased Pirh2 expression can affect the development of lung tumors by reducing the activity of the p53 protein.

    Contact: Michelle Gailiun, Ohio State University, 614-293-6054,

    Also in the November 17 JNCI:

  • Researchers Call for Studies on Role of BRCA1 Mutations in Chemotherapy Response:
  • Paclitaxel Chemotherapy for Breast Cancer Not Associated With Serious Radiation Pneumonitis:


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