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© Oxford University Press 2008.
In This Issue
Guidelines for Testing Anticancer Drugs in RodentsRodent models are commonly used to test the in vivo efficacy of new compounds that have anticancer activity in vitro. However, if experiments using such models are not designed appropriately, there is the potential for both false-negative and false-positive results—a consideration that is especially important given the cost and time needed for rodent studies and the use of these studies to determine which drugs to pursue for development. In this issue, Hollingshead (p. 1500) discusses a number of issues that should be addressed when designing experiments using rodent models, including identification of appropriate species and tumor models (and controls), selection of an appropriate vehicle, development of a treatment plan, choice of endpoints, appropriate statistical evaluation of tumor growth data, and proper presentation of the data.
Statin Use and PSA Level
The possibility that treatment with statins may be associated with the risk of prostate cancer has been the focus of many studies, but the influence of these widely used drugs on prostate specific antigen (PSA) levels was unknown. Hamilton et al. (p. 1511) addressed this question by studying 1,214 men who did not have prostate cancer at the time that they were prescribed a statin and for whom PSA results prior to and after initiation of statin treatment were available. In these men, there was a median decline in PSA levels of 4% (over a median interval of one year) that was strongly associated with statin dose and with the decline in low density lipoprotein levels. The authors suggest that the potential clinical significance of this decline for prostate cancer screening warrants further investigation.
In an accompanying editorial, Thompson et al. (p. 1487) suggest that the question of whether statins prevent and/or effectively treat prostate cancer is the most important issue, and they describe the kinds of investigations that would be needed to address this question.
X Chromosome Inactivation in Breast and Ovarian Cancer
X chromosome inactivation silences gene expression from one of the two X chromosomes in females and is usually random. Nonrandom, or skewed, X inactivation has been reported to occur more frequently in breast and ovarian cancer patients, including BRCA1 and BRCA2 mutation carriers, than in cancer-free control subjects. Lose et al. (p. 1519) used methylation-specific polymerase chain reaction amplification of the exon 1 microsatellite region of the X-linked androgen receptor gene from peripheral blood lymphocyte DNA to assess X chromosome inactivation patterns in 735 cancer-free control subjects, 313 ovarian cancer patients, 235 familial breast cancer patients who did not carry mutations in BRCA1 or BRCA2, and 323 unaffected and breast or ovarian cancer–affected BRCA1 or BRCA2 mutation carriers. Skewed X inactivation (defined as at least 90% of cells having the same active X chromosome) occurred at an increased frequency in BRCA1 (and possibly BRCA2) mutation carriers compared with control subjects and was associated with an increase in the age at diagnosis of breast and ovarian cancer. The authors suggest that skewed X inactivation may be a mechanism that favors expression of an X-linked allele that protects against cancer and that may be increased in BRCA1 mutation carriers.
Evaluating the Impact of Cancer Scale
As the population of long-term cancer survivors increases, questionnaires that accurately measure the influence of cancer on their quality of life are needed. Crespi et al. (p. 1530) conducted a refinement and psychometric evaluation of the Impact of Cancer (IOC) scale with data from 1,188 disease-free breast cancer survivors 5-10 years after their diagnosis. The questionnaires asked about demographic, treatment, and medical information and included items from the IOC scale and two other scales. The authors found patterns of association between scale scores and demographic, treatment, and medical characteristics of the breast cancer survivors that indicated good validity for the questionnaire. The authors concluded that their scale is a valid tool for measuring the impact of cancer on the quality of life of long-term cancer survivors.
Characteristics and Treatment Patterns of MDS Patients
Myelodysplastic syndromes (MDS) comprise a group of pathologically and cytogenetically distinct bone marrow disorders. Sekeres et al. (p. 1542) conducted six consecutive cross-sectional surveys of 101 hematology and medical oncology specialists in the United States between June 2005 and January 2007 via questionnaires in order to ascertain the characteristics and treatment patterns of the 4–10 most recently seen MDS patients for each physician. The physicians characterized 614–827 patients per survey. A high proportion of MDS patients were dependent on transfusions. Among recently diagnosed MDS patients, fewer patients with lower-risk disease than those with higher-risk disease were dependent on transfusions. More than half of MDS patients were treated with erythropoiesis-stimulating agents. Only a small percentage of MDS patients either had had or was being considered for bone marrow transplantation or was being treated in clinical trials. The authors suggest that the survey data may be helpful for characterizing the use of healthcare resources for MDS patients and the pharmacoeconomic impact of MDS in the United States.
Association of a Genetic Locus with Risk of Lung Cancer
Certain genetic variants in a region of chromosome 15 had been previously linked with an increased risk of lung cancer, but whether the variant alleles were associated with a tendency toward nicotine dependence, lung cancer development, or both was not clear. Spitz et al. (p. 1552) analyzed the association of one of the closely-linked variants with measures of nicotine dependence based on questionnaire responses. Individuals with the risk variant tended to smoke more and scored higher on the Fagerstrom Test for Nicotine Dependence. However, the highest risks associated with the variant were noted in the lightest smokers, and never smokers who carried the genetic variant were not at increased risk of lung cancer. The authors conclude that the risk conferred by the genetic variants, which are in a region that encompasses the nicotinic acetylcholine receptor gene cluster, are at least in part due to smoking behavior, although the results of the analysis were also consistent with direct effects of the variants on susceptibility to tobacco carcinogenesis.
In an accompanying editorial, Wacholder et al. (p. 1488) outline the challenge of interpreting genetic association data where behavioral or other kinds of intermediates may mediate a variant's effect on carcinogenesis. They suggest that investigation of molecular and behavioral mechanisms involving environmental causes of disease and formal statistical methods can aid in the interpretation of associations discovered using systematic genome-wide approaches.
Related Articles in JNCI
CiteULike 
Connotea 
Del.icio.us What's this?
J Natl Cancer Inst 2008 100: 1530-1541.
J Natl Cancer Inst 2008 100: 1519-1529.
J Natl Cancer Inst 2008 100: 1542-1551.
J Natl Cancer Inst 2008 100: 1500-1510.
J Natl Cancer Inst 2008 100: 1511-1518.
J Natl Cancer Inst 2008 100: 1552-1556.
J Natl Cancer Inst 2008 100: 1487-1488.
J Natl Cancer Inst 2008 100: 1488-1491.
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