Also in the Dec. 9 JNCI

December 09, 2008

Age-Related Crossover in Breast Cancer Incidence Between Black and White Ethnic Groups Appears Robust

Among women younger than 40 years, black women have a higher incidence of breast cancer than white women. However, among women older than 40 years, white women have a higher incidence than black women. This incidence rate "crossover" appears reproducible and reliable.

Several previous studies have reported the age-related crossover in black and white women, but some of them have suggested that it was an artifact.

In the current study, William Anderson, M.D., of the National Cancer Institute in Bethesda, Md., and colleagues reviewed data from 440,653 patients with breast cancer from the Surveillance, Epidemiology, and End Results (SEER) database.

Among women who were younger than 40 years, the incidence of breast cancer was 15.5 breast cancers per 100,000 woman-years in black women compared with 13.1 in white women. Among women who were older than 40 years, the incidence was 239.5 breast cancers per 100,000 woman-years in black women compared with 281.3 in white women.

"Although this ecologic study cannot determine the individual-level factors responsible for the racial crossover in vital rates, it confirms that the age-related crossover in breast cancer incidence rates between black and white ethnic groups is a robust age-specific effect that is independent of period and cohort effects," the authors write.

Contact: National Cancer Institute press office, ncipressofficers@mail.nih.gov, (301) 496-6641

Elevated Risk of Second Cancers for Survivors of Hereditary Retinoblastoma

Individuals who survived hereditary retinoblastoma (cancer of the retina) have an elevated risk of second cancers in middle age, relative to the general population.

Researchers know that survivors of hereditary retinoblastoma are at increased risk of second cancers, but few studies have followed these individuals into middle age.

To determine whether their excess risk continues throughout their lifetimes, Tamara Marees of the VU University Medical Center in Amsterdam, The Netherlands, and colleagues analyzed data from the Dutch retinoblastoma registry, which included 668 individuals diagnosed with retinoblastoma between 1945 and 2005.

With a median follow-up time of 22 years, Marees and colleagues found that individuals with hereditary retinoblastoma had a 20-fold greater risk of second malignancies than the general population. Survivors of 40 years and more had an absolute excess of 26.1 cases of cancer per 1,000 person-years, and half of those were epithelial cancers.

"The excess risk of epithelial cancers such as bladder and lung cancer in middle-aged retinoblastoma survivors is cause for concern and indicates that lifelong follow-up studies are needed to evaluate the full spectrum of second malignancy risk in retinoblastoma survivors," the authors conclude.

Contact: Tamara Marees, T.Marees@vumc.nl, +31 20 4444595

Noncanonical DNA Structure Associated with Genomic Instability in Mice

Chromosome breakage and translocations occur more frequently in DNA sequences that have the potential to adopt noncanonical helical structures that deviate from the familiar, right-handed helical B form.

Many cancers are associated with chromosomal breaks and translocations. Frequently these breaks occur at the site of specific genetic elements, such as repetitive DNA, or sequences that take on H-DNA or Z-DNA helical structure, instead of the more common B-DNA helical pattern.

To learn whether these differences in DNA structure induce chromosomal breakage, Karen Vasquez, Ph.D., of the University of Texas M. D. Anderson Cancer Center in Smithville and colleagues engineered mice that carry part of the c-MYC gene that forms H-DNA, or a model sequence that forms Z-DNA.

The mice carrying either the H- or Z-DNA sequences had higher mutation frequencies than control mice lacking those sequences. Large scale translocations or deletions occurred in 5 (7.7%) of the 65 mice carrying H-DNA sequences and in 7 (6.6%) of the 106 mice carrying the Z-DNA sequence, compared with none of the 63 control mice.

"These results suggest that helical distortions can result in spontaneous chromosome breakage and the translocation of genes involved in human diseases, including cancer," the authors conclude.

Contact: Scott Merville, M.D. Anderson press office, SMerville@mdanderson.org, (713) 792-0661

Fecal Occult Blood Test Associated with Reduction in Colorectal Cancer Mortality in Standard Practice Setting

Population-based colorectal cancer screening was associated with a statistically significant reduction in colon cancer deaths.

Randomized controlled trials indicated that colon cancer screening using fecal occult blood test led to a decline in disease-specific mortality. The impact of a population-based screening program has not been evaluated.

To determine the impact of a screening program, Adele Seniori Costantini, M.D., of the Institute for the Study and Prevention of Cancer in Florence, Italy, and colleagues examined colon cancer incidence and mortality in two regions of Italy that introduced screening at different times. The Empolese-Mugello district introduced screening in the early 1980s, whereas the remaining Florence and Prato provinces did so in early 2000.

Overall, there was a larger decline (13%) in colon cancer mortality in the Empolese-Mugello district compared with the rest of the Florence and Prato provinces between 1985 and 2006. Specifically, the researchers found a 2.7% decline per year in colon cancer mortality during that time in the area that introduced screening early, compared with a 1.3% per year decline in the area that introduced screening in 2000.

"Our results support the hypothesis that the observed difference in colorectal cancer mortality is due to earlier exposure to fecal occult blood test screening," the authors write.

Contact: Adele Seniori Costantini, a.seniori@ispo.toscana.it, +39 055 6268349

Expression of Chromatin Remodeling Genes Associated with Resistance to Glucocorticoid Treatment in Acute Lymphoblastic Leukemia

Expression of components of the SWI/SNF chromatin-remodeling complex is associated with resistance to glucocorticoids, such as dexamethasone and prednisolone, which are essential components of curative therapy for childhood acute lymphoblastic leukemia (ALL).

ALL patients who are resistant to dexamethasone and prednisolone have a poorer prognosis than those who respond to the drugs. The mechanism of resistance to glucocorticoids was not known.

In the current study, Meyling H. Cheok, Ph.D., of the Institut National de la Santé et de la Recherche Médicale in Lille, France, and colleagues examined the expression of genes encoding the SWI/SNF complex in ALL cells isolated from pediatric patients. The researchers compared gene expression with sensitivity to prednisolone and dexamethasone in independent training and validation cohorts.

Expression of three SWI/SNF genes was associated with resistance to the two drugs and expression of a fourth gene was associated with prednisolone resistance. Reducing the expression of SMARCA4, one of the SWI/SNF genes, in a glucocorticoid-sensitive ALL cell line increased this cell line's resistance to prednisolone.

"In conclusion, to our knowledge for the first time, we found an association between the expression of as many as three genes encoding key subunits of the SWI/SNF complex--SMARCA4, SMARCB1, and ARID1A--and resistance of ALL cells to prednisolone," the authors write.

Contact: Meyling H. Cheok, meyling.cheok@inserm.fr
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