National Cancer Institute NCI Cancer Bulletin: A Trusted Source for Cancer Research News
March 10, 2009 • Volume 6 / Number 5

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Cancer Research Highlights

Survival Benefit from Brain Cancer Regimen Persists over Time

Patients with brain cancer who received a combination of temozolomide (Temodar) and radiotherapy lived longer than those who received radiotherapy alone, and evidence of a benefit was seen in some patients for up to 5 years, according to updated results from a large clinical trial published online March 9 in The Lancet Oncology. The researchers cautioned, however, that most patients who were successfully treated with the combination therapy eventually had a recurrence and died.

In 2004, European and Canadian researchers first reported a survival benefit for patients in the EORTC-NCIC trial who received the combination therapy compared with patients who received radiation alone. Though the improvement was modest (several months), it was the first treatment advance in decades for the deadly disease. Consequently the regimen of temozolomide plus radiation became a standard treatment for glioblastoma.

The newly updated results show that at 3 years, 16 percent of patients in the temozolomide group were alive compared with only 4 percent in the radiation-alone group. At 4 years, 12 percent were alive after treatment with temozolomide compared with 3 percent for radiation therapy alone, and at 5 years, 9.8 percent were alive versus 1.9 percent, respectively.

Improvements in survival were seen in patients from all prognostic subgroups, including older patients and those whose tumors could not be removed by surgery. Among patients with more favorable prognoses, 41 percent were alive at 2 years and 28 percent at 5 years. The strongest predictor for a benefit from temozolomide was the inactivation of a gene called MGMT.

New treatments for the disease are needed, and several trials are investigating the addition of other treatments to temozolomide and radiotherapy, the researchers noted. “Until better treatments are available, radiotherapy with concomitant and adjuvant chemotherapy is the current standard of care,” they wrote.

Study Suggests Low, Moderate Alcohol Use Increases Cancer Risk

According to a new study by British researchers, low to moderate alcohol consumption among women increases their risk for numerous cancers but also appears to reduce the risk of some other cancers. The study was published online February 24 in the Journal of the National Cancer Institute.

For those cancers associated with an increased risk—breast cancer, for example, a finding that is consistent with other studies—it made no difference what type of alcohol was most frequently consumed or whether women had received hormone replacement therapy, the researchers found. However, for cancers of the upper aerodigestive tract (oral cavity, esophagus, larynx, and pharynx) the increased risk associated with alcohol intake was seen only in women who were also current smokers. The incidence of rectal and liver cancers also increased with alcohol use, while thyroid cancer, renal cell carcinoma, and non-Hodgkin lymphoma decreased.

“Although the magnitude of the excess abso­lute risk associated with one additional drink per day may appear small for some cancer sites, the high prevalence of moderate alco­hol drinking among women in many populations means that the proportion of cancers attributable to alcohol is an important public health issue,” lead author Dr. Naomi Allen from the University of Oxford and her colleagues concluded.

Their analysis involved data from nearly 1.3 million participants in the Million Women Study, which included women in the United Kingdom recruited from national breast cancer screening clinics between 1996 and 2001. Women in the study who reported drinking had an average of one drink per day, and approximately 25 percent of participants were nondrinkers.

What is not known at this point, explained Dr. Arthur Schatzkin, chief of the Nutritional Epidemiology Branch in NCI’s Division of Cancer Epidemiology and Genetics, is whether for certain women there is a trade-off in possible benefits of alcohol consumption, such as a decreased risk of cardiovascular disease, as numerous epidemiologic studies have suggested. However, it’s clear, he said, that for certain cancers, particularly of the breast, “alcohol consumption, even at moderate levels, is a modifiable risk factor.”

NCI is planning to use data from the NIH-AARP Diet and Health Study to investigate overall disease risks and benefits from low to moderate alcohol consumption, Dr. Schatzkin noted.

Chemoradiotherapy for Hodgkin Lymphoma Raises Mesothelioma Risk

The primary risk factor for malignant mesothelioma is exposure to asbestos. However, new results published online February 20 in Blood add to the evidence that radiotherapy, especially to the chest, also increases the risk. This study of long-term Hodgkin lymphoma (HL) survivors found that the risk was greatest in radiation patients who had also received chemotherapy.

A group of 2,567 patients treated for HL in the Netherlands between 1965 and 1995 were followed for a median of 18.1 years. While only eight men and five women developed mesothelioma, this rate was 25.7 times that found in the general population. Risk in women was dramatically greater (85 times the general population rate) than in men (18 times the general population rate).

The researchers also analyzed the risk according to the type of treatment the patients originally received for HL. Mesothelioma developed in only 1 of the 730 who received radiation alone (a 5.8 fold increase over the general population), and in none of the 232 patients who received chemotherapy alone. The remaining 12 patients received both treatments, and their chances of getting the disease were 44.8 times that of the general population. In all cases but one, the mesothelioma tumors developed in the field that had been irradiated during HL treatment.

Only seven of the patients had a documented history of asbestos exposure. Historically in the Netherlands, only about one in seven malignant mesothelioma patients have no history of exposure. Thus, said Dr. Marie L. De Bruin of the Netherlands Cancer Institute, “the diagnosis mesothelioma should be kept in mind whenever new symptoms arise in patients who had previous irradiation.”

Links between Genes and Smoking Confirmed

Early evidence that genes may influence a person’s use of tobacco came years ago from studies of twins. More recently, genome-wide association studies (GWAS) have explored links between genes and aspects of smoking behavior, such as the age of initiation and the amount of cigarettes smoked per day.

Building on this work, researchers have now tested associations between genes and seven key events across the spectrum of smoking behavior, from initiation through the development of dependency and health outcomes. DNA from 4,600 individuals, including 2,600 smokers, was analyzed using genome-wide and candidate gene approaches. For the candidate genes, several hundred previously identified genes suspected of playing a role were specifically evaluated.

The results confirm previous reports implicating nicotine receptor genes and genes involved in the dopamine system in the brain. In particular, a gene called MAOA, which helps break down dopamine, was strongly associated with the number of cigarettes smoked per day.

No specific chromosome regions achieved the genome-wide threshold of statistical significance, but the study provides a list of priority genes for further investigation. Reporting their findings online in PLoS One on February 27, Dr. Neil Caporaso of NCI’s Division of Cancer Epidemiology and Genetics and his colleagues said that the lack of genome-wide significant results suggests that common variants individually have at most a modest influence on smoking behavior.

“This was the first such study to look at a variety of smoking behaviors,” said Dr. Caporaso. “By identifying genes involved in smoking, we hope to develop more effective prevention and treatment strategies.” Two drugs used to help smokers quit, bupropion and varenicline, are likely to interact with targets related to genes that are associated with smoking behavior, he noted.

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