Variation in CASP8 Gene Linked to Multiple Cancers

Researchers at the Chinese Academy of Medical Sciences are reporting that a common variation in the gene CASP8 may protect against multiple cancers. The variation was associated with a reduced risk of lung, esophageal, gastric, colorectal, cervical, and breast cancers in a population of Chinese individuals, according to findings published online in Nature Genetics on April 22.

The variation is a deletion - 6 units of DNA are missing from the gene's promoter region - and this may reduce the activity of the gene in some individuals. It is not clear how the reduced activity of CASP8 may influence cancer risk. But the gene helps regulate the body's immune response, and changes to this function have been linked to variation in the risk of cancer and other diseases.

The team, led by Dr. Dongxin Lin, analyzed several genes involved in regulating the body's immune response. After discovering a link between the CASP8 deletion (called -652 6N) and a reduced risk of lung cancer, the researchers tested the deletion in nearly 5,000 individuals with cancer and a similar number of controls.

The findings support the hypothesis that genetic variation may influence the risk of cancer by modifying the activity of genes that regulate the body's response to tumors, the researchers conclude.

"This study provides additional evidence indicating that common variation in this gene is important for cancer," comments Dr. Montserrat Garcia-Closas of NCI's Division of Cancer Epidemiology and Genetics, who studies CASP8 in breast cancer. "It will now be important to independently confirm the observed associations in different populations." The deletion is thought to be fairly common in all ethnic groups.

In February, Dr. Garcia-Closas and her colleagues in the Breast Cancer Association Consortium reported that another variant in CASP8, called D302H, may confer modest protection against breast cancer. This was the first common variant to be definitively linked to breast cancer.

Dasatinib Effective in Blast-Crisis Chronic Myeloid Leukemia

Patients who enter the blast-crisis phase of chronic myeloid leukemia (BC-CML), in which 30 percent of the cells in the blood or bone marrow are immature blood cells, typically survive only 3 to 6 months. Results from 8 months of follow-up of a pair of phase II clinical trials published in the April 15 Blood show that dasatinib, a new small-molecule inhibitor that has many targets within leukemia cells, can induce lasting hematologic and cytogenetic responses in patients with BC-CML.

Investigators enrolled 42 patients with lymphoid blast crisis (LBC) and 74 patients with myeloid blast crisis (MBC) into 2 separate but identical trials. All patients were either resistant to or intolerant of imatinib, a small-molecule inhibitor used in first-line therapy of CML. Patients received a starting dose of 70 mg of dasatinib twice daily, which could be escalated after 4 weeks. Dose reductions or interruptions were allowed in response to side effects.

Patients received dasatinib until disease progression despite dose escalation, intolerable toxicity, or withdrawal from the study. Among patients with MBC, 32 percent had a major hematologic response at 6 months of follow-up; this number rose to 34 percent after 8 months. Among patients with LBC, 31 percent had a major hematologic response at both 6 and 8 months of follow-up. Twenty-seven percent of MBC patients and 43 percent of LBC patients had a complete cytogenetic response. Only 11 percent of patients with MBC and 2 percent of patients with LBC had to discontinue therapy because of side effects.

"Our results indicated that dasatinib represents a potentially important new therapeutic option for patients with imatinib-resistant or imatinib-intolerant MBC-CML or LBC-CML and will undoubtedly affect the treatment paradigm for CML," concluded the authors.

U.K. Study Links Ovarian Cancer to Hormone Use

Women who use hormone replacement therapy (HRT) have an increased risk of developing ovarian cancer and dying from the disease, a large British study reports. The risk increases the longer HRT is used, but risk returns to the level seen in women who have never used hormones, once HRT is stopped. The participants were from the Million Women Study, and about 500,000 of the women had taken HRT.

Women who were currently using HRT were on average 20 percent more likely to die from ovarian cancer than those who had never received HRT. Since 1991, the researchers estimate, HRT use has led to an additional 1,000 deaths from ovarian cancer, as well as an additional 1,300 new diagnoses of ovarian cancer in the United Kingdom.

The findings should be considered along with studies linking HRT use to endometrial and breast cancers, the researchers say. The incidence of these three cancers in the study population was 63 percent higher in current users of HRT than in never users, according to findings published online in The Lancet on April 19.

"When ovarian, endometrial, and breast cancer are taken together, use of HRT results in a material increase in the incidence of these common cancers," writes Dr. Valerie Beral of the Epidemiology Unit at Cancer Research UK in Oxford and her colleagues.

Although use of HRT has declined greatly in recent years, enormous numbers of women have been exposed. "With these new data on ovarian cancer, we expect the use of HRT to fall further," says Dr. Steven Narod of Women's College Research Institute, Toronto, in an accompanying editorial.

Nursing Lecture Describes Dietary Interventions and Physical Activity for Cancer Patients

Dietary interventions and physical activity can help patients manage cancer-related weight changes and nutritional deficiencies during and after treatment, according to Dr. Jean K. Brown, interim dean and professor at the University at Buffalo School of Nursing. Dr. Brown presented the April 17 CCR Grand Rounds lecture, a special oncology nursing lecture.

Dr. Brown cited two recent studies linking dietary counseling to improved nutritional outcomes. She also noted that "nutraceuticals" - food or food components that provide medical or health benefits - have been shown to lessen cancer-related nutritional problems and increase survival. A diet that includes nutraceuticals such as fatty acids, plant-derived polyphenols, and antioxidants should be considered for cancer patients, Dr. Brown commented.

"To intervene around nutritional issues, one needs to use a multimodal approach," Dr. Brown said. "You can't just try to improve food intake." She highlighted a clinical trial which found that nutritional counseling plus indomethacin and erythropoietin increased food intake, body fat, maximum exercise capacity, and, ultimately, survival.

Dr. Brown noted that physical activity can also improve cancer outcomes. During and after treatment, exercise has been associated with improved cardiorespiratory fitness, quality of life, and a decrease in treatment-related symptoms, such as reduced functional capacity, fatigue, and depression, she said.