NCI Cancer Bulletin: A Trusted Source for Cancer Research NewsNCI Cancer Bulletin: A Trusted Source for Cancer Research News
October 19, 2004 • Volume 1 / Number 40 E-Mail This Document  |  Download PDF  |  Bulletin Archive/Search  |  Subscribe

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Cancer Research HighlightsCancer Research Highlights

Birth Weight, Childhood Growth, and Breast Cancer

In women, body size has been correlated with risk for breast cancer. Obese women, for example, have a lower risk before menopause and higher risk after, and tall women are generally at higher-than-average risk for breast cancer. Now, researchers at the Danish Epidemiology Science Center and Copenhagen's Institute of Preventive Medicine have traced these trends back to adolescence and childhood. This research, supported by the U.S. Department of Defense Congressionally Directed Medical Research Programs, the Danish Medical Research Council, the Danish National Research Foundation, and the Danish Cancer Society, is published in the October 14 New England Journal of Medicine.

Danish schools track students' birth weight; annual weight and height; and, for girls, age at first menstrual period. These records are entered in a civil registration system and can be linked with registries for cancer patients. In this study, researchers examined medical records from a cohort of Danish women who attended school in Cophenhagen and were born between 1930 and 1975, 117,415 of whom had complete records on height and weight at 8, 10, 12, and 14 years of age, and 3,340 of whom eventually developed breast cancer. A comparison of these cases with a control group of 5,500 medical records showed that the risk for breast cancer, after adjusting for body mass index (BMI), correlates directly with birth weight, with height at 8 years of age, and with growth rate between the ages of 8 and 14 years, but correlates inversely with BMI at age 14.

The study authors suggest that timing of breast differentiation may be a factor in these trends, noting that puberty marks the start, and first pregnancy the final stage, of breast cell differentiation - a point at which they become more resistant to carcinogenesis. "Overall," the authors write, "our results provide evidence that factors influencing fetal, childhood, and adolescent growth are important independent risk factors for breast cancer in adulthood."

Fruit, Vitamin C Protect Against Stomach Cancer

New data from a large prospective nutrition study indicate that a diet high in fruit may protect against the most common form of stomach cancer. The findings - presented by NCI researchers on Oct. 17 at the American Association for Cancer Research's (AACR) "Frontiers in Prevention" conference - showed that, at 12 years follow-up, a diet high in fruit and vitamin C, as well as gamma-tocopherol, a form of vitamin E, and lycopene, an antioxidant found in high concentrations in tomatoes, were protective against gastric noncardia cancer (GNCC). The strongest preventive associations were for fruit and vitamin C consumption.

"These results confirm findings on fruit and vitamin C from many other studies," said one of the study's lead investigators, Dr. Farin Kamangar, a visiting fellow in the NCI Center for Cancer Research (CCR). "As a result, we believe that fruit and vitamin C are likely to be useful for the prevention of stomach cancer. As for lycopene, we need to wait for further results that confirm these findings before we can say whether there is sufficient evidence of a protective effect."

The report offers the most recent findings from the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study, led by NCI and the Finland Institute of Public Health. The study, conducted from 1985-1993, involved more than 29,000 male Finnish smokers and initially focused on lung cancer prevention. In this recent analysis, despite the apparent positive effects of gamma-tocopherol in preventing GNCC, high dietary intake of gamma- and alpha-tocopherol were associated with a slightly elevated increased risk of the less-common form of stomach cancer, gastric cardia cancer. The finding that different antioxidants have disparate effects according to gastric cancer type, Dr. Kamangar and colleagues concluded, should be taken into account in the design of future prevention trials.

Inactivating MYC Gene Returns Liver Tumor Cells to Normal Function

Some liver cancer tumor cells return to their normally functioning states and liver tumors undergo significant regression when a single oncogene is inactivated, according to a study published online on October 10 by Nature. Working in a transgenic mouse model of hepatocellular carcinoma, a form of liver cancer that often fails to respond to existing treatments, Stanford University researchers found that when the MYC oncogene was inactivated with the antibiotic doxycycline, not only did the tumors completely regress in 30 days, but some tumor cells also resumed normal function. "Upon MYC inactivation, most of the liver tumor cells are able to differentiate into hepatocytes and biliary cells, forming bile duct structures," the researchers wrote.

To confirm that MYC inactivation was indeed responsible for this activity, the research team, led by Dr. Dean W. Felsher, and funded in part by NCI, reactivated the gene. The result: tumor growth resumed. Using a technology known as array comparative genomic hybridization, the researchers determined that the newly active tumor cells were genetically identical to those that had become dormant after MYC inactivation.

The researchers cautioned that "liver cancer may respond differently than other tumors to oncogene inactivation, because the liver has the intrinsic ability to regenerate itself, demonstrating that the liver maintains stem cells." Because the liver tumor cells "retained the ability to differentiate into multiple hepatic lineages," they argued, these particular cells may represent "dormant cancer stem cells."