National Cancer Institute NCI Cancer Bulletin: A Trusted Source for Cancer Research News
April 7, 2009 • Volume 6 / Number 7

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Cancer Research Highlights

Ovarian Cancer Screening Resulted in Many Unnecessary Surgeries

Screening women for ovarian cancer often led to unnecessary surgeries and failed to detect the disease in its early stages, according to new results from the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial. The analysis focused on the 34,000 women in the NCI-sponsored trial who were screened annually for signs of ovarian cancer using transvaginal ultrasound and/or the CA-125 blood test.

Many of the positive screening results turned out not to be cancer. The researchers estimate that out of every 100 women who test positive for signs of ovarian cancer with these tests, only 1.6 actually have cancer. In another measure of the screening program, the ratio of surgeries to detected cancers over all four rounds of screening was 19.5 to 1.

Screening effectively doubled the rate of oophorectomy (removal of the ovaries) among this group, which included women aged 55 to 74 years old. Screening with transvaginal ultrasound accounted for most of the unnecessary surgeries, but this method also detected the most early stage cancers. Overall, however, 70 percent of the ovarian cancers found in the study were in their late stages (stage III or later), when treatment options are limited.

The results are consistent with the current guidelines of the U.S. Preventive Services Task Force that do not recommend ovarian cancer screening with CA-125 and transvaginal ultrasonography, the researchers concluded in the April Obstetrics & Gynecology. The question of whether the screening program saves lives will be addressed in future studies that include results from women who did not undergo screening.

"We need a test that is more sensitive and more specific so we find the cancer earlier and we catch the biological markers that give us stronger clues," lead investigator Dr. Edward Partridge, who directs the University of Alabama at Birmingham Comprehensive Cancer Center, said in a statement. He discussed the findings in a short video here.


Racial Disparity in Colon Cancer Linked to p53 Gene

African Americans have the highest incidence and mortality from colon cancer of any ethnic or racial group in the United States. Researchers have investigated differences in diet, alcohol consumption, socioeconomic factors, and physical activities as possible explanations for these disparities. Because genetic and biological differences may also play a role, some researchers are looking for markers that predict the aggressiveness of tumors and clinical outcomes.

A new study suggests that the p53 gene, which normally helps to suppress tumors and is frequently mutated in cancer, could be such a marker. A form of the gene called Pro72 was more common in African Americans than Caucasians in the study, and the variant was associated with an increased number of p53 mutations, more advanced tumors, and shorter survival time compared with other forms of the gene.

If the results are confirmed, Pro72 could be a prognostic marker and eventually lead to more personalized treatments for people who carry this form of the p53 gene, said Dr. Upender Manne of the University of Alabama at Birmingham and his colleagues in the April 1 Clinical Cancer Research.

The study included 137 African Americans and 236 Caucasians. Both groups had similar rates of p53 mutations, but 17 percent of the African Americans carried two copies of the Pro72 variant compared with 7 percent of Caucasians. The presence of this variant in African Americans was associated with a more than twofold increase in mortality due to colorectal cancer. The variant had no effect on mortality from colorectal cancer among Caucasians.

In the subset of patients with colorectal cancer who inherit the Pro72 variant, the susceptibility to disruptive changes in the p53 protein may be a possible molecular explanation for the racial disparity, the researchers concluded.


Multifocal Lung Tumors May Arise from a Single Cell

In a small percentage of patients with lung cancer, multiple tumors that look similar under the microscope can arise in several parts of the lung, either synchronously (at the same time) or metachronously (in succession). Whether these multifocal tumors arise from a single malignant cell or form separately due to widespread carcinogenic effects on the lung tissue—from exposure to tobacco smoke, for example—has not been clear.

A new study led by researchers from Indiana University and published online April 7 in the Journal of the National Cancer Institute provides genetic evidence indicating that the majority of these cancers may arise from a single cell and should therefore be classified as advanced-stage cancers.

The researchers collected formalin-fixed, paraffin-embedded tissue samples from 30 patients (23 women and 7 men) with multifocal lung cancer, for a total of 70 separate tumor samples. Three different types of genetic changes were analyzed in the tumor samples: loss of genetic material on several chromosomes; mutations in a gene called TP53; and epigenetic changes on the X chromosomes in samples taken from women.

Complete concordance, or an identical loss of genetic material among multifocal tumors, was seen in 26 out of 30 patients. Out of 18 patients whose samples could be screened for TP53 mutations, 10 had identifiable mutations, and in 8 patients these mutations were identical among multifocal tumors. Out of 19 women whose tumor samples could be used for epigenetic analysis, 15 had a concordant pattern of changes between multifocal tumors.

When results of the three analyses were combined, "23 (77 percent) of 30 patients had identical genetic changes, consistent with a monoclonal origin of these separate tumors rather than separate independent primary lung tumors. Our findings support the current classification of multifocal lung cancers as advanced-stage cancers…rather than separate primary cancers and the use of therapeutic strategies tailored for patients with advanced-stage cancers," concluded the authors.


Alcohol-induced Flush Warns of Esophageal Cancer Risk

"Asian flush," a response to alcoholic beverages caused by a buildup of acetaldehyde, is most often seen in Japanese, Chinese, and Koreans who are unable to metabolize alcohol effectively. It is also strongly associated with risk for esophageal cancer: People who turn red after drinking have a dramatically higher risk of developing the disease than those who don't flush.

In the March issue of PLoS Medicine, study authors Dr. Philip Brooks of the National Institute on Alcohol Abuse and Alcoholism, and his collaborators at Duke University and the National Hospital Organization Kurihama Alcoholism Center in Japan wrote that because flushing is easily apparent and also strongly linked with cancer risk, it should be a routine cancer screening factor in primary care settings.

They noted that 36 percent of East Asians, or approximately 540 million people worldwide, carry a defective copy of the gene for aldehyde dehydrogenase 2 (ALDH2), the enzyme that helps break down acetaldehyde, a product of ethanol metabolism, into acetate. Acetaldehyde is strongly carcinogenic, the authors explained.

People who carry two defective copies of the ALDH2 gene are usually unable to drink significant amounts of alcohol due to the severity of their reaction. However, those who have only one defective copy of the gene can develop tolerance, and prospective studies have shown that the risk for developing cancers in the upper aerodigestive tract is approximately 12 times higher in these individuals. Furthermore, because acetaldehyde lingers in saliva, particularly in those who smoke, they are at an even greater risk for cancer.

Pointing out other social trends that pose increased risk among this population, the authors wrote, "Clinicians need to be aware of the risk of esophageal cancer from alcohol consumption in their ALDH2-deficient patients…[and should] determine whether an individual of East Asian descent is ALDH2 deficient simply by asking whether they have experienced the alcohol flushing response."

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