| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© Oxford University Press 2007.
IN THIS ISSUE
Arsenic in Drinking Water and Cancer Trends in ChileArsenic in drinking water is known to cause several cancers, including bladder and lung cancer. However, the latency period between exposure and cancer onset has not been determined, nor has the extent of the risk increase. Marshall et al. (p. 920) investigated these questions by taking advantage of a unique situation in Chile: one region of the country experienced a dramatic rise in arsenic water concentration beginning in 1958 and a subsequent decline in the 1970s. The authors compared lung and bladder cancer mortality over a 50-year period in this region with mortality in a similar region that did not experience an increase in arsenic levels. Mortality from these cancers began to increase about 10 years after the region's arsenic exposure increased and remained high for the next 40 years, long after the exposure level had dropped. At their peaks, the lung cancer mortality rate was increased by three- to fourfold in both men and women, and the bladder cancer mortality rate was increased by sixfold in men and 14-fold in women.
In an editorial, Lubin et al. (p. 906) note that large numbers of people worldwide are exposed to levels of inorganic arsenic in their drinking water that exceed the generally accepted standard of 10 µg/mL. They point out that the temporal patterns observed by the authors are intriguing but caution that analytic epidemiologic studies will be required to gain a better understanding of the mechanisms of arsenic carcinogenesis.
BRCA2 and Risk of Aggressive Prostate Cancer in Iceland
BRCA2 gene mutations are associated with an increased risk of prostate cancer. To determine whether the Icelandic BRCA2 999del5 founder mutation is associated with prostate cancer progression and mortality, Tryggvadóttir et al. (p. 929) used Iceland population-based registries to identify relatives of breast cancer patients who had been diagnosed with prostate cancer from 1955 through 2004. Each prostate cancer patient with the BRCA2 mutation was matched to two patients without the mutation by year of diagnosis and year of birth. The BRCA2 mutation was associated with a more advanced tumor stage and grade, a younger age at diagnosis, a shorter survival time, and an increased risk of dying from the disease. The authors conclude that the Icelandic BRCA2 999del5 founder mutation is associated with an aggressive and lethal form of prostate cancer.
In an editorial, Wacholder et al. (p. 908) write that the results may help to elucidate the role of BRCA2 mutations in prostate cancer tumorigenesis and improve the quality of information given to patients at diagnosis. However, they note that application of these findings is limited due to problems that are common in studies of this type: a small number of mutation carriers, changes in screening over time, and the assumption that the date of diagnosis corresponds to the date of disease onset. They suggest that genome-wide studies to determine the association between genetic factors and effectiveness of cancer therapies may improve treatment for patients.
Candidate Oncogene in Human Glioblastoma Multiforme
Identifying genes that control glioblastoma multiforme progression may help researchers devise new therapies, which are needed because patients currently have a median survival of only 12–15 months. Ng et al. (p. 936) investigated the involvement of the cell cycle–related kinase gene (CCRK) in glioblastoma multiforme tumorigenesis. CCRK mRNA levels were elevated in 74% of the samples from patients with high-grade glioblastoma multiforme and in 80% of the glioma cell lines examined compared with levels in normal brain tissue. Suppression of CCRK with small interfering RNA inhibited the proliferation of two glioblastoma cell lines in a time- and dose-dependent manner and led to cell cycle arrest at the G1/S phase and reduced phosphorylation of cyclin-dependent kinase 2. Reduced CCRK expression in a subcutaneous nude mouse xenograft model suppressed growth of glioma cells. The authors conclude that CCRK is a candidate oncogene in glioblastoma multiforme tumorigenesis and a potential target for therapies.
Antitumor Activity, Deguelin, and Heat Shock Protein 90
Deguelin, a natural plant product that is used as an insecticide, has shown antitumor activity, but its mechanism of action is not known. Oh et al. (p. 949) investigated deguelin's mechanism of action by examining xenograft mouse model systems of five human cancers. They found that tumor-bearing mice treated with deguelin showed a statistically significant decrease in tumor growth; the drug induced apoptosis and the degradation of proteins that require heat shock protein 90 (Hsp90) for their stability and function. Computer modeling of the interaction between deguelin and Hsp90 and binding inhibition experiments showed that deguelin binds to the ATP-binding pocket of Hsp90. The authors conclude that the antitumor activity of deguelin appears to involve its binding to the ATP-binding pocket of Hsp90, which leads to the suppression of Hsp90 function.
AIDS-Related Cancers, CD4 Counts, and Antiretroviral Therapy
The incidence of acquired immunodeficiency syndrome (AIDS)-related cancers (Kaposi sarcoma, non-Hodgkin lymphoma, and cervical cancer) has been declining among persons with AIDS since the introduction of highly active antiretroviral therapy (HAART) in 1996. Biggar et al. (p. 962) investigated the association between cancer risk and CD4 cell count (a reflection of immunosuppression) among AIDS patients treated before and after the HAART era. The incidence of Kaposi sarcoma and non-Hodgkin lymphoma decreased after the introduction of HAART, but cervical cancer incidence increased. The risk of Kaposi sarcoma and non-Hodgkin lymphoma—but not cervical cancer—was associated with the patient's CD4 cell count at the onset of AIDS. The authors conclude that the decreasing incidence of Kaposi sarcoma and non-Hodgkin lymphoma in persons with AIDS during the 1990s is consistent with improving CD4 counts after the introduction of HAART.
Related Articles in JNCI
CiteULike 
Connotea 
Del.icio.us What's this?
J Natl Cancer Inst 2007 99: 920-928.
J Natl Cancer Inst 2007 99: 929-935.
J Natl Cancer Inst 2007 99: 949-961.
J Natl Cancer Inst 2007 99: 962-972.
J Natl Cancer Inst 2007 99: 936-948.
J Natl Cancer Inst 2007 99: 906-907.
J Natl Cancer Inst 2007 99: 908-909.
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||