© 2001 by Oxford University Press
Journal of the National Cancer Institute, Vol. 93, No. 10, 731,
May 16, 2001
© 2001 Oxford University Press
IN THIS ISSUE |
Five large studies of women living primarily in the northeastern United States were funded in 1993 to evaluate a possible association between the risk of breast cancer and plasma or serum levels of organochlorines. The analysis included DDE [1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene], a major metabolite of the pesticide DDT, and PCBs (polychlorinated biphenyls), a group of industrial chemicals manufactured in the United States until the 1970s. In this issue, Laden et al. (p. 768) present their combined analysis of these studies. They did not find an association between the risk of breast cancer and plasma or serum concentrations of PCBs or DDE. Thus, they conclude that exposure to these compounds, as measured in adult women, is unlikely to explain the high rates of breast cancer in the northeastern United States.
"Exposure to DDE and PCBs, as measured in adult women, is unlikely to explain the high and increasing rates of breast cancer experienced in the northeastern United States."
—Laden et al.
Hormone Replacement Therapy After a Breast Cancer Diagnosis
Hormone replacement therapy (HRT) is usually avoided for women who have had breast cancer because estrogen in HRT might, in theory, increase their risk of a breast cancer recurrence. In this issue, O’Meara et al. (p. 754) report their analysis of the impact of HRT on recurrence and mortality in women after a diagnosis of breast cancer. They found lower risks of recurrence and mortality in women who used HRT after a breast cancer diagnosis than in women who did not. Although residual confounding may exist, their results suggest that use of HRT after a diagnosis of breast cancer has no adverse impact on recurrence or mortality.
In an editorial, Cuzick (p. 733) notes that, although HRT use is often avoided in women with breast cancer, the better survival of women diagnosed while on HRT and the observations by O’Meara et al. raise doubts about the wisdom of this policy. He urges that these results be investigated in randomized trials.
"Should this beneficial effect [of HRT use] be confirmed in randomized studies, the hormonal treatment of breast cancer will require very major reevaluation."
—Cuzick
Angiogenesis, Lysophosphatidic Acid, and Ovarian Cancer
Vascular endothelial growth factor (VEGF) is a potent endothelial cell-specific growth factor that stimulates angiogenesis, which is critical for cancer growth. VEGF is expressed both in primary ovarian cancers and ovarian cancer cell lines and is important in the formation of ascites in ovarian cancer patients. Because lysophosphatidic acid (LPA) stimulates ovarian cancer growth, Hu et al. (p. 762) assessed whether it does so via VEGF-induced angiogenesis. The authors compared the responses to LPA in three ovarian cancer cell lines and one immortalized ovarian surface epithelial cell line. LPA increased expression of VEGF in all the cancer cell lines but not the immortalized cell lines through the transcriptional activation of the VEGF promoter. Only the ovarian cancer cell lines expressed the LPA receptor Edg4. The authors concluded that LPA plays a role in ovarian cancer growth, in part by stimulating VEGF expression.
In an editorial, Folkman (p. 734) discusses the link between LPA, VEGF expression, and angiogenesis in ovarian cancer, and he stresses the distinction between the classes of angiogenesis inhibitors and their varying clinical implications.
A Novel Compound Against Head and Neck Cancer
Many investigative agents that are potentially useful in treating and preventing a variety of cancers are associated with toxicity; 1
,25-dihydroxyvitamin D3, in particular, can cause overabsorption of calcium, or hypercalcemia. Prudencio et al. (p. 745) investigated the utility of EB1089, a vitamin D3 analogue with demonstrated activity against laboratory models of breast and prostate cancers, in inhibiting growth of head and neck cancer cells in culture and in cell culture-derived tumors implanted in mice. They found that EB1089 inhibited the growth of cultured head and neck cancer cells and implanted tumors; it was both more effective in this activity than 1,25-dihydroxyvitamin D3 and not associated with hypercalcemia. The authors also investigated the molecular mechanisms of EB1089 action. They conclude that their findings, combined with previously published studies, indicate that vitamin D3 analogues may act to prevent genomic instability associated with cancer progression as well as to block cell proliferation.
Resistance to Apoptosis and Proliferative Breast Disease
Proliferative breast disease, a sequence of morphologic changes including hyperplasia, is associated with an increased risk of breast cancer. Starcevic et al. (p. 776) used a series of breast cell lines that recapitulates these morphologic changes and examined the sensitivity of these cells to apoptosis and the levels of various proteins associated with apoptosis in these cells. They found that resistance to apoptosis developed progressively in their cell series and that levels of proteins associated with apoptosis changed accordingly. Thus, the cells that most rapidly developed atypical hyperplasia and carcinoma in situ in vivo were the most resistant to apoptosis.
Body Fat, Hormones, and Prostate Cancer Risk
Body fat distribution is controlled, in part, by the hormones insulin and leptin. Because Chinese men with a higher waist-to-hip ratio (WHR) have a higher risk of prostate cancer, Hsing et al. (p. 783) examined whether insulin and leptin were associated with risk of prostate cancer. Using data from a population-based, case–control study of Chinese men, the authors found that, after adjusting for body mass index, WHR, insulin-like growth factor-I, and sex hormone levels, higher serum insulin levels were associated with an increased risk of prostate cancer. Compared with men in the lowest tertiles of WHR and insulin levels, men in the highest tertiles of WHR and insulin levels had an 8.55-fold risk of prostate cancer. The authors found no association between leptin and prostate cancer risk. They conclude that serum insulin levels may influence the risk of prostate cancer in Chinese men.
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