© Oxford University Press 2006.
IN THIS ISSUE
Chornobyl Accident and Subsequent Thyroid CancerChildren and adolescents exposed to radioactive iodine have an increased risk of thyroid cancer. To quantify this risk, Tronko et al. (p. 897) analyzed data from the first screening round of the first cohort study of individuals who were under age 18 when exposed to fallout from the 1986 Chornobyl accident. A cohort of 32,385 individuals who lived in highly contaminated areas were invited for thyroid screening in 1998–2000. Among the 13,127 individuals who were screened, 45 cases of thyroid cancer were found. Individual thyroid dose estimates were available from thyroid activity measurements made shortly after the accident and interview data. The authors observed a strong linear relationship between thyroid cancer and individual thyroid dose, with an excess relative risk of 5.25 per Gy. The authors estimate that approximately 75% of the cases would not have occurred in the absence of the Chornobyl accident.
Premature Menopause in Survivors of Childhood Cancer
Women who survive childhood cancer and retain ovarian function have a higher chance of developing menopause before age 40 than women without such a history. To determine the risk of premature menopause in childhood cancer survivors, Sklar et al. (p. 890) assessed the incidence of premature menopause in 2819 female childhood cancer survivors and 1065 female siblings in the Childhood Cancer Survivor Study. The authors found that the cumulative incidence of nonsurgical premature menopause was 8% in survivors and 0.8% in siblings. They also identified factors associated with the increased risk of premature menopause in cancer survivors. The authors conclude that these results will facilitate counseling survivors about their risk of premature menopause and aid in developing new treatments to reduce ovarian toxicity.
In a related editorial, Chen and Manson (p. 880) discuss the potential health consequences of premature menopause for women's health and highlight future research needs.
Breast Cancer Outcome, p53 Expression, and MDM2
The MDM2 gene is overexpressed in some cancers. A common single-nucleotide polymorphism in the MDM2 promoter region, SNP309, leads to increased expression of the Mdm2 protein and decreased function of the p53 tumor suppressor protein. Boersma et al. (p. 911) investigated whether genetic variations in MDM2 were associated with breast cancer incidence and survival and whether the variant status of MDM2 could interact with the tumor p53 status to modify breast cancer survival. Although they did not observe an association between SNP309 status and breast cancer incidence, they did find an association between breast cancer survival and another MDM2 SNP. They also observed a statistically significant interaction between SNP309 and tumor p53 status for breast cancer survival. The authors conclude that the strong interaction between SNP309 and tumor p53 status appears to modify the association between p53 status and breast cancer survival.
Clotting Factors, Tamoxifen, and Thromboembolic Events
In the National Surgical Adjuvant Breast and Bowel Project's Breast Cancer Prevention Project (BCPT), women who took tamoxifen had a higher risk of thromboembolic events, such as deep vein thrombosis and pulmonary emboli, than women who took a placebo. To determine whether specific mutations in two proteins involved in blood clotting, Factor V Leiden and prothrombin, were associated with the increased risk, Abramson et al. (p. 904) compared the mutation status of 76 women in the BCPT who had experienced thromboembolic events with that of 295 women who did not. No associations were observed between mutation status and the incidence of thromboembolic emboli, although women who experienced thromboembolic emboli had a higher body mass index than women who did not. The authors conclude that screening women at risk for breast cancer for the Factor V Leiden and prothrombin mutations is not useful in determining their risk of tamoxifen-associated thromboembolic events.
Body Size and Risk of Colon and Rectal Cancer
In men, body weight and body mass index are directly associated with a higher risk of colon cancer; in women, there is no association. To determine whether this difference is related to fat distribution, Pischon et al. (p. 920) examined associations between body size and weight and the risk of colon and rectal cancer among 368,277 men and women participating in the European Prospective Investigation Into Cancer and Nutrition. The authors found associations between body weight and body mass index and the risk of colon and rectal cancer among men but not women. However, waist circumference and waist-to-hip ratio were associated with colon cancer risk in both sexes. For men and women with the largest waist-to-hip ratios, the estimated 5-year absolute risks of developing colon cancer were 203 and 129 per 100,000; for those with the smallest ratios, the risks were 131 and 86 per 100,000. The authors conclude that abdominal obesity was associated with colon cancer risk in this population.
Designing Antiangiogenic Molecules to Fight Tumors
Treating cancer by inhibiting angiogenesis would be greatly advanced by agents that are selective, potent, easily administered, and inexpensive. Dings et al. (p. 932) have taken a novel approach to designing such agents. Using the cyclic compound calix[4]arene as a two-sided molecular scaffold, they added various hydrophobic and hydrophilic substitutents to each side. The goal was to create a molecule that approximated the dimensions, composition, and surface features of the antiangiogenic peptide anginex while avoiding some of the limitations of peptides as pharmacologic agents. Two novel calixarene-based compounds were found to inhibit endothelial cell proliferation and migration and to reduce angiogenesis in chick embryos, and their potencies were similar to or greater than that of anginex. In mouse models, these molecules decreased tumor growth and microvessel density without apparent side effects. The authors suggest that the promising results from these new angiogenesis inhibitors warrant their eventual study in the clinic.
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||