© 2002 by Oxford University Press
Journal of the National Cancer Institute, Vol. 94, No. 4, 239,
February 20, 2002
© 2002 Oxford University Press
IN THIS ISSUE |
There is growing evidence supporting an association between infection with the JC virus (JCV, a neurotropic polyomavirus) and human brain tumors, including medulloblastomas. Del Valle et al. (p. 267) assessed the presence of JCV Agno gene sequences in a series of 20 well-characterized medulloblastomas. They also determined the expression of agnoprotein and cellular structural and regulatory proteins, including the JCV early gene product, T-antigen. Analysis of amplified DNA from tumor samples revealed the presence of the Agno gene in 69% of samples tested and immunohistochemical cytoplasmic localization of agnoprotein in 55% samples tested. JCV T-antigen was present in the nucleus of some, but not all, of the neoplastic cells. Tumor samples expressing agnoprotein did not always show expression of T-antigen. The finding of agnoprotein expression in the absence of T-antigen suggests that agnoprotein may have a potential role in the pathways involved in the development of JCV-associated medulloblastomas.
In an editorial, Fine (p. 240) agrees that the assertions made by Del Valle et al. are provocative, but he suggests that the role JCV plays in the pathogenesis of medulloblastomas is yet to be determined definitively. He recommends that current data regarding the genetic mechanisms by which JCV can transform cells in vitro and in vivo should be critically evaluated and compared with the mechanisms shown to be operative in the pathogenesis of medulloblastomas.
Effects of Raloxifene After Tamoxifen in a Mouse Model
The recommended treatment for women with early stage breast cancer is 5 years with the selective estrogen receptor modulator (SERM) tamoxifen, which reduces breast cancer recurrence and mortality. However, treatment with tamoxifen for more than 5 years doubles a woman’s risk of endometrial cancer without further reducing her risk of breast cancer recurrence. O’Regan et al. (p. 274) studied the effects of raloxifene, another SERM, on the growth of tumors derived from human breast and endometrial cancer cells that were previously unexposed or exposed to tamoxifen in athymic, ovariectomized mice in the presence or absence of low-dose estrogen. They found that raloxifene and tamoxifen had similar stimulatory effects on the growth of breast and endometrial tumors that had been exposed to tamoxifen in the past. The authors conclude that raloxifene treatment after 5 years of tamoxifen may not further decrease breast cancer recurrence but may increase the incidence of endometrial cancer.
In an editorial, Sporn (p. 242) discusses the limitations of adjuvant therapy with single agents for the treatment of breast cancer. He suggests that future pharmacologic approaches to cancer should be based on new advances in cell biology and should investigate the efficacies of novel combinations of chemotherapeutic agents.
Race/Ethnicity and Non-Small-Cell Lung Cancer
Among patients diagnosed with advanced non-small-cell lung cancer, African-Americans have lower survival rates than non-African-Americans. Blackstock et al. (p. 284) used data from phase II and phase III Cancer and Leukemia Group B trials, in which patients were treated with similar systemic therapies, to assess whether the difference in survival was related to innate characteristics in the two ethnicities or to disparities in health care. The authors found that African-Americans had a statistically significantly lower 1-year survival rate than non-African-Americans, but the effect of race/ethnicity disappeared after adjustments were made for measures of tumor burden such as performance status and weight loss. The authors also found that African-American patients were more likely than non-African-American patients to be unmarried, disabled, unemployed, and Medicaid recipients. The authors conclude that because of the relationship between tumor burden and socioeconomic status, social circumstances led to African-Americans presenting with poorer prognostic features.
Economic Analysis of Treatments for Lung Cancer
Nearly 170,000 people are diagnosed with lung cancer annually in the United States, so it is important to determine the economic impact of new cancer therapies. Ramsey et al. (p. 291) performed an economic analysis alongside a Southwest Oncology Group trial to estimate the cost-effectiveness of standard therapy (cisplatin plus vinorelbine) versus new therapy (carboplatin plus paclitaxel) for patients with advanced non-small-cell lung cancer. Throughout the observation period, the researchers noted that the average cost per participant for the treatment with carboplatin plus paclitaxel was substantially more expensive than the treatment with cisplatin plus vinorelbine ($48,940 versus $40,292). There was no difference in survival or quality of life between treatments. The majority of the cost difference was a result of the extra cost of the drugs in protocol chemotherapy. Ramsey et al. did not observe notable differences in costs of blood products, supportive care medications, non-protocol-related inpatient or outpatient care, or nonprotocol chemotherapy.
Gene Polymorphisms, Smoking, and Pancreatic Cancer Risk
Carcinogens present in cigarette smoke are thought to contribute to the twofold increased risk of pancreatic cancer that is associated with cigarette smoking. Duell et al. (p. 297) studied the associations between polymorphisms in the gene that encodes human cytochrome P-450 1A1 (CYP1A1), an enzyme responsible for metabolizing such carcinogens; homozygous deletions in the genes encoding two glutathione S-transferases, GSTM1 and GSTT1, enzymes that protect cells from carcinogen-related cell damage; smoking; and the risk of pancreatic cancer. The authors found that none of the polymorphisms themselves affected pancreatic cancer risk among the Caucasian subjects. However, compared with never-smokers with the GSTT1-present genotype, women and men with the GSTT1-null genotype who were heavy smokers had fivefold and 3.2-fold increased risks, respectively, of pancreatic cancer. The authors conclude that heavy smoking combined with a null mutation of GSTT1 is associated with an increased risk of pancreatic cancer among Caucasians.
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