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© Oxford University Press 2007.
IN THIS ISSUE
Possible Tumor Suppressor and Aggressive Prostate Cancer RiskThe genetic factors that underlie the risk or progression of prostate cancer are largely unknown. In an exploratory study, Duggan et al. (p. 1836) analyzed 60,000 single-nucleotide polymorphisms (SNPs) for associations with a diagnosis of aggressive prostate cancer. The exploratory study identified seven candidate SNPs. Further testing in two cohorts—one composed of individuals of European descent and the other of African Americans—suggested that a possible tumor suppressor gene, DAB2IP, was in fact associated with an increased risk of aggressive prostate cancer.
In an editorial, Hsieh et al. (p. 1823) discuss experimental findings that implicate DAB2IP in the progression of prostate cancer and its possible role in signal transduction mechanisms that modulate cell proliferation and death.
Radiologist Characteristics and Diagnostic Mammograms
Radiologists are known to have high vari-ability in their interpretation of screening mammograms, but less is known about the variability in interpretation of diagnostic mammography. Miglioretti et al. (p. 1854) examined the performance of 123 radiologists who interpreted 35,895 diagnostic mammograms at 72 facilities that contribute data to the Breast Cancer Surveillance Consortium. They found considerable variation in interpretative performance across radiologists that was not explained by the characteristics of the patients. The authors conclude that this variability is concerning and likely affects many women with and without breast cancer. They recommend investigating ways of improving the interpretation of diagnostic mammography.
Extended Adjuvant Therapy for Postmenopausal Breast Cancer
Clinical trial data have shown that women who received 5 years of the nonsteroidal aromatase inhibitor letrozole after 5 years of adjuvant tamoxifen experienced a 42% reduction in the risk of breast cancer recurrence compared with women who received a placebo. However, the long-term efficacy and safety of extended adjuvant treatment were not examined because the trial was stopped early. Jakesz et al. (p. 1845) conducted a prospective randomized open-label clinical trial—Austrian Breast and Colorectal Cancer Study Group (ABCSG) Trial 6a—to compare the efficacy and tolerability of adjuvant therapy with another aromatase inhibitor, anastrozole, among patients who were disease free at the end of ABCSG Trial 6. That trial showed that tamoxifen alone was not superior to tamoxifen plus the aromatase inhibitor aminoglutethimide as an adjuvant therapy for patients with hormone receptor–positive postmenopausal breast cancer. At a median follow-up of more than 5 years, adjuvant therapy with 3 years of anastrozole reduced the risk of breast cancer recurrence by 38% in women who had taken tamoxifen for 5 years compared with no further treatment. Anastrozole was well tolerated, and no unexpected adverse events were reported.
In an editorial, Prowell and Stearns (p. 1825) review three approaches that have been used to incorporate aromatase inhibitors into adjuvant treatment for postmenopausal breast cancer. They discuss factors that should be considered when deciding on the duration of adjuvant endocrine therapy following tamoxifen and an aromatase inhibitor.
Cancer Incidence Over Time in Blood Transfusion Recipients
Blood transfusions can expose recipients to biologic agents that are known or suspected to be associated with cancer occurrence. They may also alter recipients’ immune systems, thereby increasing their risk for some cancers. Hjalgrim et al. (p. 1864) used computerized blood bank and health data to examine cancer rates among blood transfusion recipients in Sweden and Denmark. They observed a marked increase in the relative risk of most cancers and cancer overall during the first 6 months after transfusion, but the risk decreased over time to approach that of the general population. The risk for cancers that are associated with tobacco and alcohol use remained elevated for 10–20 years after the blood transfusion. The marked increase in cancer risk shortly after blood transfusion may reflect the presence of undiagnosed cancers that prompted the transfusion. The lasting risk of tobacco- and alcohol-related cancers suggests that lifestyle and other risk factors related to the conditions prompting transfusion—rather than transfusion-related exposures themselves—are important to the observed cancer occurrence in the recipients.
Understanding Trends in Prostate Cancer Incidence and Mortality
Using the high-quality cancer incidence and mortality data available in the Nordic countries, Kvåle et al. (p. 1881) analyzed trends in national prostate cancer incidence and mortality rates, focusing on the period from 1980 to 2004. Increases in prostate-specific antigen (PSA) screening in the Nordic countries beginning in the early 1990s account for increases in prostate cancer incidence that were observed over the same period. A stabilization or decline in prostate cancer mortality within the last decade was also seen, which is consistent with the moderate effects of increased detection and/or improvements in treatment. However, the authors conclude that the specific contributions of PSA screening and treatment of early and advanced disease remains to be determined.
Cancer Risk for Heterozygotes with the Founder NBN Mutation
Nijmegen breakage syndrome (NBS) is a recessive chromosomal instability disorder that is associated with an increased risk of lymphoid malignancies and other cancers. More than 90% of NBS patients are homozygous for a founder mutation, 657del5, in the NBN gene. Seemanova et al. (p. 1875) conducted a family study of 344 blood relatives (first through fourth degree) in 24 NBS families in the Czech Republic and Slovakia. Thirteen of these relatives had confirmed cases of cancer, and 11 of the 13 carried the 657del5 mutation. This cancer incidence was several times higher than expected. The authors conclude that the NBN founder mutation 657del5 appears to be associated with an elevated cancer risk in heterogyzous carriers.
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Del.icio.us What's this?
J Natl Cancer Inst 2007 99: 1854-1863.
J Natl Cancer Inst 2007 99: 1845-1853.
J Natl Cancer Inst 2007 99: 1864-1874.
J Natl Cancer Inst 2007 99: 1881-1887.
J Natl Cancer Inst 2007 99: 1836-1844.
J Natl Cancer Inst 2007 99: 1875-1880.
J Natl Cancer Inst 2007 99: 1823-1824.
J Natl Cancer Inst 2007 99: 1825-1827.
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