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© Oxford University Press 2007.
IN THIS ISSUE
Choline, One-Carbon Metabolism, and Colorectal AdenomaOne-carbon metabolism is a network of biochemical pathways that plays a central role in the synthesis, repair, and modification of DNA and may therefore have a role in carcinogenesis. Epidemiologic studies have suggested that decreased intake of folate and methionine and increased intake of alcohol—all dietary factors involved in one-carbon metabolism—are associated with an increased risk of colorectal adenoma, a precursor of colorectal cancer. Choline and betaine also are important factors in one-carbon metabolism, but their effect on colorectal adenoma risk was not known. Cho et al. (p. 1224) assessed the relationship between these dietary factors and the risk of colorectal adenoma based on biannual questionnaires sent to over 39,000 women enrolled in the Nurses’ Health Study. Contrary to expectations, high dietary intake of choline was associated with an increased risk of colorectal adenoma. There was no clear association between betaine intake and colorectal adenomas. The authors suggest that more study is needed to determine if choline consumption itself or another dietary component closely associated with choline intake accounts for the increased risk of colorectal adenoma.
In an editorial, Ziegler and Lim (p. 1214) suggest that one-carbon metabolism and its role in carcinogenesis is more complicated than originally anticipated. They write that more research—and caution in developing public health policy and guidance—is warranted.
Arterial Thromboembolic Events and Treatment with Bevacizumab
An increased risk of arterial thromboembolism has been observed in some trials of bevacizumab and chemotherapy versus chemo-therapy alone. Scappaticci et al. (p. 1232) investigated this risk in a pooled analysis of five randomized controlled clinical trials that included 1,745 patients with various types of metastatic cancer. The combined treatment with bevacizumab and chemotherapy was associated with an increased risk for arterial thromboembolism but not for venous thromboembolism compared with chemotherapy alone. The absolute rate of developing arterial thromboembolism was 5.5 per 100 person-years with the combination therapy and 3.1 per 100 person-years with chemotherapy alone. The risk of developing arterial thromboembolism was associated with a prior arterial thromboembolic event or an age of 65 years or older. The authors conclude that the risk of arterial thromboembolism is modestly increased with the combination therapy and that risk factors for arterial thromboembolism should be taken into consideration when making treatment decisions.
Liver Cancer Chemoprevention and Vitamin/Mineral Combinations
Liver cancer is increasingly common worldwide, especially in the developing world. Given the high mortality rate of liver cancer patients, prevention may be an important strategy to control deaths from this disease. The Linxian General Population Trial was a randomized factorial trial designed to examine the effects of four vitamin–mineral combinations on the risk of several cancers in residents of rural China. The follow-up duration is now sufficient for the effects on liver cancer mortality to be evaluated. Qu et al. (p. 1240) report that none of the combinations reduced mortality from liver cancer overall. However, the combination of retinol and zinc appeared to reduce mortality in younger participants, as did the combination of riboflavin and niacin. The combination of molybdenum and vitamin C reduced mortality in men but not women. The authors note that the people of Linxian have an inadequate intake of many vitamins and minerals, so it is unclear whether these findings would apply to a nutrient-replete population.
Mortality after Second Cancers in Testicular Cancer Survivors
Patients with testicular cancer undergo treatments that put them at increased risk of developing second cancers. However, the mortality rates of survivors due to their second cancers are unknown. Schairer et al. (p. 1248) analyzed Surveillance, Epidemiology, and End Results program data of 621 white testicular cancer survivors who developed second cancers. They compared the survivors’ mortality rates with those of more than 12,000 white males with first cancers who were matched by cancer site, stage, year of diagnosis, and age at diagnosis. During the study period, from 1973–2002, 284 patients with second cancers died, 191 from their cancer. The mortality rates for patients with second cancers and first cancers were similar overall. However, when the analyses were restricted to whose testicular cancer was diagnosed between 1973 and 1979, a period when treatment for testicular cancer involved high dose radiotherapy, the risk of death due to second cancers at sites that may have been irradiated during the original treatment was higher than that for matched first cancers.
Lung Cancer Classification by Profiling of Adjacent Tissue
Changes in cytokine gene expression in surrounding noncancerous tissue as well as in tumors have been used as biomarkers to predict prognosis and metastasis in hepatocellular carcinoma. Seike et al. (p. 1257) examined whether the cytokine gene expression profile of noncancerous lung tissue could predict the metastatic capability of the adjacent lung adenocarcinoma. A signature of 11 genes—called the Cytokine Lung Adenocarcinoma Survival Signature (CLASS-11)—accurately classified stage I lung adenocarcinoma patients according to their risk of death. The profile was based on both lung tumors and adjacent noncancerous tissue. The authors conclude that this cytokine gene signature may be useful for determining which lung adenocarcinoma patients are at high risk of death.
Epigenetic Loss of Imprinting of the IGF2 gene in Wilms Tumors
The most common genetic or epigenetic alteration in Wilms tumor is loss of imprinting (LOI) of the IGF2 gene. LOI of IGF2 occurs in approximately half of all Wilms tumors. Bjornsson et al. (p. 1270) examined 59 Wilms tumor samples to determine whether LOI of IGF2 is associated with relaxation of imprinting at loci other than IGF2 or with widespread alterations in DNA methylation. Epigenetic alterations in Wilms tumors were not widespread, supporting the gene and lineage specificity of LOI of IGF2. The authors conclude that IGF2 might be a good target for the development of drugs to treat Wilms tumors.
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J Natl Cancer Inst 2007 99: 1240-1247.
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J Natl Cancer Inst 2007 99: 1214-1215.
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