Other highlights in the November 16 JNCI

Increased physical activity is associated with decreased breast cancer risk in both black women and white women, a new study has found.

Dozens of studies have examined the association between recreational physical activity and breast cancer. However, questions remain about whether a reduction in risk is observed in all population subgroups. To examine the association between physical and activity and breast cancer in black and white women, Leslie Bernstein, Ph.D., of the University of Southern California Norris Comprehensive Cancer Center in Los Angeles, and colleagues examined data from a case-control study of more than 8,000 black women and white women ages 35 to 64.

They found that, among all women, increased levels of lifetime exercise activity were associated with decreased breast cancer risk. This inverse association did not differ between black and white women. They also noted that no modification of risk was observed by disease stage, estrogen receptor status, or any breast cancer risk factor other than history of breast cancer in a first-degree family member. In women who had a first-degree family member with breast cancer, physical activity was not associated with decreased risk of breast cancer.

Contact: Jon Weiner, Director of Media Relations, (323) 442-2823, jonweine@usc.edu

Plant Compound May Block Tobacco-Induced Lung Cancer Development, Animal Study Shows

Deguelin, a natural plant product, may interfere with the development of tobacco-induced lung cancer by interfering with the cellular processes that turn normal cells cancerous.

Previous studies have found that deguelin inhibits the proliferation of premalignant and malignant human bronchial epithelial cells by inhibiting the activation of a cellular pathway called P13K/Akt, which helps cancerous cells survive. Ho-Young Lee, Ph.D., of the University of Texas M. D. Anderson Cancer Center in Houston, and colleagues treated mice with deguelin to determine whether deguelin could block tobacco-induced lung tumorigenesis, which occurs through Akt activation.

They found that deguelin decreased Akt activation and the number of tobacco-induced lung tumors in the treated mice compared with untreated mice with no detectable toxicity. The authors conclude that deguelin should be considered for testing as a chemopreventive agent for early stages of lung carcinogenesis.

In an editorial, Stephen S. Hecht, Ph.D., of the University of Minnesota Cancer Center in Minneapolis, points out the difficulties in designing mouse models of tobacco-induced lung carcinogenesis that can then be applied to current and former smokers. That said, he writes, "the work reported by Lee et al., as well as that being carried out in other laboratories, holds some promise for new approaches to lung cancer chemoprevention."

Contact: Article: Laura Sussman, Communications Office, M. D. Anderson Cancer Center, 713-745-2457, lsussman@mdanderson.org
Editorial: Mary Lawson, UMN Public Relations, 612-624-6165, mlawson@umn.edu

Study Examines Association Between Colorectal Cancer Risk and Levels of Fat Cell Hormone

High plasma levels of adiponectin, an insulin-sensitizing hormone secreted by fat cells, are associated with a decreased risk of colorectal cancer, a new study has found.

Adiponectin concentrations are inversely associated with body fat (that is, people with higher amounts of body fat tend to have lower circulating levels of adiponectin), and low levels of adiponectin are associated with insulin resistance and hyperinsulinemia. To determine whether plasma levels of adiponectin are associated with the risk of colorectal cancer, Esther K. Wei, Sc.D., of the Channing Laboratory at Brigham and Women's Hospital in Boston, and colleagues compared the baseline plasma adiponectin levels of 179 men in the Health Professionals Follow-up Study who developed colorectal cancer with those of 356 men who did not develop cancer.

They found that men with the highest plasma adiponectin levels had a lower risk of developing colorectal cancer than men with the lowest plasma adiponectin levels. The inverse association remained even after adjusting for various measures of body fatness and other colorectal cancer risk factors. The authors conclude that more studies--particularly in women, who tend to have higher circulating levels of adiponectin than men--are needed to fully understand the relationship between adiponectin and carcinogenesis.

Contact: Melaine Franco, media relations manager, Brigham and Women's Hospital, (617) 534-1605, mfranco1@partners.org

Diabetes Associated With Increased Risk of Colorectal Cancer, Meta-Analysis Finds

Having diabetes is associated with an increased risk of colorectal cancer, according to a new meta-analysis.

Most, but not all, studies of diabetes and colorectal cancer risk have found a positive association between the conditions. The findings have also been inconclusive with regard to sex and colorectal subsite. To resolve these inconsistencies, Susanna C. Larsson, M.Sc., of the Karolinska Institute in Stockholm, and colleagues conducted a meta-analysis of published data on the association between diabetes and the incidence and mortality of colorectal cancer.

They found that having diabetes was associated with a 30% increased risk of colorectal cancer compared with not having diabetes. These results were consistent between case-control and cohort studies and between studies conducted in the United States and Europe. They found that the association between diabetes and colorectal cancer incidence did not differ by sex or by cancer subsite. Diabetes was also positively associated with colorectal cancer mortality, but that result varied among the studies included in the analysis.

Contact: Susanna Larsson, susanna.larsson@ki.se

Researchers Develop Vaccine That Mimics Effects of Monoclonal Antibody

A new study reveals that it is possible to create a vaccine that mimics the effect of an epidermal growth factor receptor (EGFR) inhibitory antibody but eliminates the need to repeatedly administer this antibody over long periods of time, as is the case with some currently available therapies.

The monoclonal antibody cetuximab (Erbitux), which is approved for the treatment of metastatic colon cancer, inhibits EGFR signaling. However, it must be repeatedly administered to maintain its antitumor effects. Erika Jensen-Jarolim, M.D., Angelika B. Riemer, M.D., Ph.D., and colleagues at the Medical University of Vienna examined whether they could create a vaccine that induces the continuous production of cetuximab-like antibodies in mice. Their strategy involved using mimotopes, small peptides that mimic a specific region of a protein called an epitope.

They found that their vaccine exerted antitumor activity and that the induced antibodies inhibited the growth of EGFR-expressing cells to a similar extent as cetuximab. The authors conclude that epitope-specific immunization is feasible in mice and that the mimotope-induced antibodies have similar biologic properties as the monoclonal antibody cetuximab.

Contact: Erika Jensen-Jarolim, Medical University of Vienna, +43 1 40400 5103, erika.jensen-jarolim@meduniwien.ac.at

Study Examines Effect of Hysterectomy on Endometrial Cancer Rates

Previous reports of endometrial cancer rates in the United States have substantially underestimated the occurrence of endometrial carcinoma among women with a uterus in the United States because women who have had hysterectomies were included in the population at risk, a new study finds.

In the United States, reported rates for endometrial carcinoma are substantially higher among white women than among black women, a surprising disparity given that obesity, a strong risk factor for endometrial carcinoma, is more prevalent among blacks. However, the observation that hysterectomy prevalence is higher among young blacks compared with whites suggests that hysterectomy prevalence by race may contribute to an inflated estimate of the racial disparity in endometrial carcinoma rates. In addition, black women who undergo hysterectomy tend to be more obese than those who retain their uteri, whereas this difference is not found among whites. (Women who have had their uterus removed cannot develop cancer of the endometrium, the lining of the uterus.)

Mark E. Sherman, M.D., of the National Cancer Institute, and colleagues estimated corrected endometrial carcinoma rates by using data from the Surveillance, Epidemiology, and End Results program and the Behavioral Risk Factor Surveillance Survey.

They found that correcting for hysterectomy prevalence increased age-adjusted endometrial carcinoma rates per 100,000 women over the 9 year-period 1992-2000 from 29.2 to 48.7 (a 66.8% increase) overall, from 14.6 to 28.5 (a 95.3% increase) in blacks, from 18.8 to 29.6 (a 57.6% increase) in Hispanics, and from 33.2 to 54.8 (a 65.1% increase) in white non-Hispanics. The uncorrected white:black rate ratio decreased from 2.27 to 1.93 with correction for prevalence of hysterectomy. Failure to correct for hysterectomy prevalence may lead to underestimates of endometrial carcinoma risk, especially among blacks. In addition, the high prevalence of hysterectomy among blacks with strong endometrial cancer risk factors may partly account for lower rates in this group, the authors conclude.

Contact: NCI Press Office, 301-496-6641, ncipressofficers@mail.nih.gov

Also in the November 16 JNCI:

• Tamoxifen Reduces Risk of Breast Cancer, Follow-Up Study Confirms:
• Researchers Uncover Cellular Clues to Vitamin A Resistance in Lung Cancer: http://www.eurekalert.org/emb_releases/2005-11/jotn-ruc111005.php

Note: The Journal of the National Cancer Institute is published by Oxford University Press and is not affiliated with the National Cancer Institute. Attribution to the Journal of the National Cancer Institute is requested in all news coverage. Visit the Journal online at http://jncicancerspectrum.oxfordjournals.org/.