© 2005 Oxford University Press
IN THIS ISSUE
MGMT Promoter Methylation in Sporadic Colorectal CancerSporadic colorectal cancers often arise from a region of cells characterized by a "field defect"—cells that appear normal but have an underlying molecular defect. The promoter of the DNA repair gene O6-methylguanine-DNA methyltransferase (MGMT) is frequently methylated in colorectal tumors. Shen et al. (p. 1330) used three different techniques to detect MGMT promoter methylation in 95 colorectal cancer patients and in 33 subjects with no evidence of cancer. They found that 46% of the tumors had MGMT promoter methylation. Patients whose tumors had MGMT promoter methylation also had substantial MGMT promoter methylation in apparently normal adjacent mucosa. In grossly normal colonic mucosa of colon cancer patients, MGMT promoter methylation was detected 10 cm away from the tumor in 10 of 13 cases. The authors conclude that some colorectal cancers arise from a field defect defined by DNA methylation–mediated epigenetic inactivation of MGMT.
In an editorial, Giovannucci and Ogino (p. 1317) discuss whether promoter methylation of MGMT (or of other relevant genes) could be useful as a marker for early detection and risk assessment in colon cancer or as an intermediate marker for etiologic studies, the possible differential effects of chemopreventive approaches and study designs depending on methylation status, and whether reversal of DNA methylation in precancerous cells may prevent the development of new primary cancers in the same organ.
-Carotene and the Risk of Tobacco-Related Cancers
To determine if -carotene intake is associated with the risk of cancer in women, Touvier et al. (p. 1338) followed 59,910 French women who reported their dietary, medical, and smoking status in 1994 as participants in a prospective cohort study. After a median follow-up of 7.4 years, the authors determined the risk of tobacco-related cancers among women by their dietary -carotene intake and -carotene supplement use, according to smoking status. Among never smokers, cancer risk decreased with increased -carotene intake in a dose-dependent fashion (181.8 cases versus 81.7 cases per 10,000 women over 10 years in the low- versus high-intake groups, respectively). However, among ever smokers, cancer risk was highest among women in the high-intake group (174 cases versus 368.3 cases per 10,000 women over 10 years in the low- versus high-intake groups, respectively).
In an editorial, Mayne and Lippman (p. 1319) discuss the modification by tobacco exposure of the chemopreventive effects of nutrients and potentially other agents and the contributions and limitations of the Touvier et al. study. They conclude that recommendations for daily intake of fruits and vegetables should not be changed and that new cancer prevention trials should separately analyze current, former, and never smokers.
Anti–Helicobacter pylori Therapy for Gastric Lymphoma
To determine the efficacy of Helicobacter pylori eradication therapy in low-grade early-stage gastric mucosa-associated lymphoid tissue (MALT) lymphoma and in high-grade transformed tumors (DLBCL[MALT]), Chen et al. (p. 1345) examined the results of two studies of the treatment conducted in Taiwan. One study enrolled 34 patients with MALT lymphoma from March 1996 through April 1999 and the other enrolled 24 patients with DLBCL(MALT) from June 1995. All patients were followed through January 31, 2004. After 2 weeks of antibiotic therapy, H. pylori was eradicated in 97% of patients with low-grade tumors and in 92% of those with high-grade tumors; complete tumor response was observed in 80% and 64% of the low- and high-grade patients, respectively. The authors conclude that large-scale prospective studies should be performed to validate the use of anti–H. pylori therapy as a first-line therapy for early-stage H. pylori–positive DLBCL(MALT).
Second Cancers Among Testicular Cancer Patients
Although second primary cancers are a leading cause of death among men with testicular cancer, few studies have investigated risks among long-term survivors of testicular cancer. Travis et al. (p. 1354) identified 40,576 1-year survivors of testicular cancer in 14 population-based tumor registries in Europe and North America and obtained data on new incident solid tumors among these patients from 1943 through 2001. They found that 2285 second solid cancers had been reported in this cohort. The relative risk and excess absolute risk of second cancers decreased with increasing age at testicular cancer diagnosis; with attained age, the excess absolute risk increased but the excess relative risk decreased. They concluded that testicular cancer survivors are at increased risk of solid tumors for at least 35 years after treatment and that young patients may face increasing levels of risk as they reach older ages.
Hormone Therapy and Mammographic Density
Increased mammographic density reduces the sensitivity of screening mammography and may be hormone-related. McTiernan et al. (p. 1366) assessed the effect of hormone (estrogen plus progestin) therapy on mammographic density in a racially and ethnically diverse ancillary study of the Women's Health Initiative by analyzing data from 413 postmenopausal women who had been randomly assigned to receive hormone therapy or placebo daily. They found that the mean percent mammographic density increased by an absolute 6% over baseline mammographic density the first year in women receiving hormone therapy but decreased almost 1% in women receiving placebo. After 2 years, the mean changes persisted but were attenuated in both groups. The authors concluded that use of hormone therapy for up to 2 years was associated with increases in mammographic density.
Mapping of a Susceptibility Locus in Malignant Melanoma
The genetics of familial cutaneous malignant melanoma (CMM) and ocular malignant melanoma (OMM) are largely unknown. In this issue, Jönsson et al. (p. 1377) report the results of a genome-wide scan of Danish pedigrees with multiple cases of OMM, CMM, and other malignancies to identify melanoma susceptibility genes. Linkage to chromosome 9q21.32 was observed in the three families that were studied. The authors also examined tumor tissue from 10 sporadic CMM lesions for expression of RASEF, a known gene in this region. Expression was found to be decreased in 70% of these tumors compared with RASEF expression in a human reference RNA pool and in 10 breast cancer tumors. The authors conclude that a novel susceptibility locus maps to chromosome 9q21 in families at high-risk of developing OMM and CMM.
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