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© Oxford University Press 2007.
IN THIS ISSUE
Endotoxin Exposure and Lung Cancer in Female Textile WorkersLung cancer rates are reduced among workers in the cotton textile industry. To investigate whether this reduction is associated with exposure to bacterial endotoxin contamination, Astrakianakis et al. (p. 357) carried out a nested case–cohort study within a group of 267,400 female textile workers in Shanghai, China. Workers with a cumulative exposure to bacterial endotoxin contamination had a reduced risk of lung cancer, compared with workers who were not exposed. After 20 years of endotoxin exposure, lung cancer incidence was reduced by approximately 7.6 cases per 100,000 women in this worker population, compared with 19.1 cases per 100,000 in the general population of women in Shanghai. The authors conclude that long-term, high-level endotoxin exposure appears to be associated with a reduced risk of lung cancer in this group. They note that a plausible biologic mechanism may relate to innate and acquired immune responses that are triggered by exposure to high levels of this bacterial protein.
In an editorial, Boffetta (p. 339) writes that these results suggest endotoxin exposure is associated with a reduced risk of lung cancer. However, a stronger conclusion is precluded by potential confounding and a limited understanding of how endotoxins may reduce the risk of developing lung cancer. Great caution should be exercised when moving from the results of observational studies of complex mixtures to conclusions about interventions aimed at cancer prevention.
Cardiovascular Disease Risk Among Long-Term Breast Cancer Survivors
Radiation therapy given to breast cancer patients in the 1970s has been associated with an increased risk of cardiovascular disease among survivors. To determine whether modern radiation treatment regimens (i.e., those introduced in the early 1980s) are also associated with increased risk, Hooning et al. (p. 365) compared cardiovascular disease incidence among 10-year breast cancer survivors treated with radiation with that among both non-irradiated patients and the general population. Radiation to the internal mammary chain was associated with an increased risk of valvular dysfunction and congestive heart failure among patients treated in 1970–1979 and in 1980–1986, whereas the risk of myocardial infarction was increased during the earlier period but not during the later period. The association between radiotherapy and risk of myocardial infarction was stronger among smokers than nonsmokers. The authors conclude that radiotherapy for breast cancer as received from 1980 onward may be associated with an increased risk of cardiovascular disease and that smoking may be associated with additional risk.
In a related editorial, Giordano and Hortobagyi (p. 340) encourage researchers to investigate the long-term toxicities of modern breast cancer therapies to prevent reductions to patient quality of life.
Selective Estrogen Receptor Modulators as Multifunctional Medicines
After the recent success of tamoxifen and raloxifene as preventive treatments for breast cancer, Jordan (p. 350) provides a historical overview of the development—in the laboratory and in clinical trials—of the concept of selective estrogen receptor modulation. SERMs exert target tissue–specific effects on estrogen signaling, and these drugs have become the basis for the treatment and prevention of both breast cancer and osteoporosis. The author summarizes the results of the major clinical trials—including the Study of Tamoxifen and Raloxifene—that address the safety and effectiveness of tamoxifen and raloxifene as chemopreventive treatments for breast cancer, osteoporosis, and coronary heart disease and discusses the prospects for and obstacles to further progress in chemoprevention.
PSA-Activated Therapies as a Treatment for Prostate Diseases
Prostate-specific antigen (PSA) is a protease that is secreted by both the normal and diseased prostate but not by other tissues or organs. Drugs that are activated by PSA-catalyzed cleavage may be potential therapies for diseases of the prostate gland, including benign prostatic hyperplasia and prostate cancer. Williams et al. (p. 376) synthesized a PSA-activated protoxin, PRX302, and tested it in models of prostate cancer. PRX302 selectively decreased the viability of PSA-expressing prostate cancer cell lines and slowed growth of PSA-expressing tumor xenografts in mice when injected directly into the tumors. PRX302 injected directly into the PSA-expressing prostate glands of cynomolgus monkeys caused extensive, but organ-confined, damage. The authors conclude that PRX302 is safe and potentially effective for the treatment of localized prostate disease.
Changes in Breast Density Over Time and the Risk of Breast Cancer
High breast density as measured during screening mammography is associated with an increased risk of breast cancer. Kerlikowske et al. (p. 386) sought to determine whether a change in breast density over time was associated with increased breast cancer risk by analyzing data from more than 300,000 women who underwent breast density assessments during screening mammography. An increase in measured breast density over several years was predictive of an increased risk, and decreased density was predictive of decreased risk. This pattern held true for all women except those who were in the highest breast density category at the initial examination. The authors suggest that temporal changes in breast density could be useful in predicting breast cancer risk.
EXT1 Gene, Tumor Supression, and Nonhereditary Osteochondromas
Exostosis (multiple)-1 (EXT1) is a gene known to cause Multiple Osteochondromas, a rare hereditary syndrome that is characterized by the formation of cartilage-capped bony neoplasms (osteochondromas). However, it is not known whether the EXT1 gene is also involved in the development of nonhereditary osteochondromas, which are far more common. Hameetman et al. (p. 396) subjected eight nonhereditary osteochondromas—and the cartilage cap, perichondrium, and bony stalk of one of these osteochondromas—to various molecular analyses to determine whether EXT1 acts as a classical tumor suppressor gene for nonhereditary osteochondromas. Seven of eight osteochondromas had lost both alleles of EXT1; these homozygous EXT1 deletions were present only in the cartilage cap of an osteochondroma. The authors conclude that EXT1 functions as a classical tumor suppressor gene in the cartilage cap of nonhereditary osteochondromas.
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Del.icio.us What's this?
J Natl Cancer Inst 2007 99: 357-364.
J Natl Cancer Inst 2007 99: 339.
J Natl Cancer Inst 2007 99: 340-341.
J Natl Cancer Inst 2007 99: 350-356.
J Natl Cancer Inst 2007 99: 357-364.
J Natl Cancer Inst 2007 99: 365-375.
J Natl Cancer Inst 2007 99: 376-385.
J Natl Cancer Inst 2007 99: 386-395.
J Natl Cancer Inst 2007 99: 396-406.
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