National Cancer Institute NCI Cancer Bulletin: A Trusted Source for Cancer Research News
September 21, 2010 • Volume 7 / Number 18

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Cancer Research Highlights

Mutations Linked to Two Uncommon Forms of Ovarian Cancer

Mutations in a gene called ARID1A may play a key role in the development of two types of ovarian cancer, according to studies published online September 8 in the New England Journal of Medicine (NEJM) and September 8 in Science Express.

In the NEJM study, Canadian researchers found ARID1A mutations in 55 (46 percent) of 119 samples of ovarian clear-cell carcinoma, which accounts for about 12 percent of U.S. ovarian cancer cases, as well as in 10 (30 percent) of 33 samples of endometrioid carcinoma, another relatively uncommon type of ovarian cancer. No mutations were found in samples from patients with the most common type of ovarian cancer, serous carcinoma, which accounts for about 70 percent of U.S. ovarian cancers.

In the Science Express study, which was smaller but very similar, researchers from Johns Hopkins Sidney Kimmel Comprehensive Cancer Center reported ARID1A mutations in 57 percent of ovarian clear-cell carcinoma tumor samples.

Both ovarian clear-cell and endometrioid carcinoma are associated with endometriosis, a gynecologic condition in which cells that line the uterus proliferate in other nearby areas, often producing severe pelvic pain and other problems. Neither cancer subtype responds well to available therapies.

“Connecting ARID1A gene mutations to endometriotic lesions accelerates us toward the development of tools to determine which women with endometriosis are at increased risk for ovarian cancer,” said the NEJM study’s senior author, Dr. David Huntsman from the British Columbia Cancer Agency, in a news release.

His research team initially identified seven types of ARID1A mutations in a small (discovery) set of 19 clear-cell and endometrioid carcinoma samples and then confirmed the findings in an additional (validation) set of 211 ovarian cancer samples. When the researchers looked more closely at two patients whose clear-cell carcinoma tumors had ARID1A mutations, they found the mutations in nearby endometriotic lesions but not in lesions farther away from the primary tumor. Taken together, the research team wrote, the evidence suggests that ARID1A mutations “may be pathogenic, rather than random, events” and are “an early event in neoplastic transformation.”

The findings, Dr. Huntsman said, via e-mail, suggest that earlier studies implicating the gene in cancer were correct and that ARID1A “appears to be a tumor-suppressor gene of considerable relevance."

Declines in U.S. Smoking Prevalence Stalled

After a period of marked downturns in smoking prevalence in the United States during the 1990s and the early 2000s, smoking rates have held steady for the past 5 years, CDC researchers report. According to their analysis of data from the 2009 National Health Interview Survey and the 2009 Behavioral Risk Factor Surveillance System, 20.6 percent of U.S. adults age 18 and older were regular smokers in 2009, virtually unchanged from the 20.9 percent who were regular smokers in 2005. The findings appeared in the September 10 Morbidity and Mortality Weekly Report (MMWR).

Consistent with previous surveys, smoking rates were somewhat higher among men than women, and there were still dramatic disparities in smoking according to region of the country, income level, and education. For example, smoking prevalence in 2009 among people age 25 and older who did not finish high school compared with those who obtained a graduate degree were 28.5 percent and 5.6 percent, respectively.

Another report in the July 9 MMWR showed that the declines in youth smoking have slowed, but they have not stalled. From 2003 to 2009, smoking among high school students declined by 11 percent, compared with a 40-percent decline from 1997 to 2003. Nearly one in five U.S. high school students reported smoking, the 2009 survey found.

“The slowing in the decline observed for youth cigarette smoking indicates that cigarette smoking among adults and the associated morbidity and mortality will continue to be important public health issues for the foreseeable future,” wrote Dr. Shanta R. Dube and her colleagues from the CDC’s National Center for Chronic Disease Prevention and Health Promotion in their September report.

Both the Patient Protection and Affordable Care Act and the 2009 Family Smoking Prevention and Tobacco Control Act provide “new opportunities” for reducing tobacco use, the researchers wrote. Under the former, access to evidence-based smoking-cessation services and treatments is expected to expand, and the Tobacco Control Act “gives the [FDA] authority to regulate the manufacturing, marketing, and distribution of tobacco products.”

Men with Low PSA Levels May Not Benefit from Further Prostate Cancer Screening

Also in the Journals: PSA Levels and Prostate Cancer Screening

By studying Swedish men who provided blood samples at age 60 and were followed for 25 years, researchers have found that the concentration of prostate-specific antigen (PSA) in the blood at that age was associated with the risk of developing life-threatening prostate cancer later in life. Although men with a concentration below the median (≤1 ng/mL) might harbor prostate cancer, the cancer was unlikely to be fatal. “These men could be exempted from further screening, which should focus on men with higher concentrations,” Dr. Hans Lilja of Memorial Sloan-Kettering Cancer Center and his colleagues reported online September 15 in the British Medical Journal (BMJ).

A second report, also online in BMJ, analyzed data from six randomized trials, involving more than 380,000 men, to assess the benefits and harms of prostate cancer screening. The analysis did not support the routine use of PSA testing with or without digital rectal exam. “Screening leads to an increase in the diagnosis of early-stage prostate cancer that does not seem to translate into a benefit in overall survival and survival specific to prostate cancer,” concluded Dr. Philipp Dahm of the University of Florida College of Medicine in Gainesville, FL, and his colleagues.

Together with the observational study in Cancer by van Leeuwen and colleagues showing a low risk of prostate cancer mortality among men ages 55 to 74 with a PSA level of 0.0-1.9ng/mL, there is accumulating evidence that it may be possible to identify a group at very low risk for prostate cancer death, experts in NCI’s Division of Cancer Control and Population Sciences said.

Men age 55 to 74 who have a low level of prostate-specific antigen (PSA) in their blood may not benefit from further screening or treatment for prostate cancer, according to a study led by Dr. Pim van Leeuwen of the Erasmus University Medical Center in the Netherlands. The study results were published online September 13 in Cancer.

To better understand the potential benefit-to-harm ratio of PSA screening, the researchers compared prostate cancer incidence and mortality among 42,503 unscreened men in Northern Ireland with the incidence and mortality among 43,987 screened men who participated in the European Randomized Study of Screening for Prostate Cancer (ERSPC), a 2009 study that suggested PSA screening could reduce prostate cancer deaths by 20 percent. (The researchers could not compare PSA levels between the screened and control arms of the ERSPC study because baseline PSA levels were not collected for men in the control group.)

Men in both groups were divided into four baseline PSA categories (0.0 to 1.9 ng/mL; 2.0 to 3.9 ng/mL; 4.0 to 9.9 ng/mL; and 10.0 to 19.9 ng/mL) and were followed for a median of approximately 9 years. Men with PSA levels 20 ng/mL or higher were excluded from the study.

In the unscreened Northern Ireland group, 236 men died from prostate cancer during the follow-up period, compared with 109 men in the ERSPC group. This translated to a 20-percent relative reduction in prostate cancer-specific mortality with screening after adjusting for age and baseline PSA, a finding similar to the one previously reported using ERSPC data alone. However, the reduction was not evenly distributed across the four categories.

“A negligible difference in the cumulative hazard in prostate cancer death was observed for men with PSAs [less than 3.9 ng/mL] at study entry,” stated the authors. The number of men who would need to undergo treatment to prevent one death from prostate cancer ranged from 60 men in the highest baseline category (10.0 to 19.9 ng/mL) to 725 men in the lowest (0.0-1.9 ng/mL).

The study had several limitations, explained the authors, including the lack of randomization between the two groups studied, a large difference in all-cause mortality between the groups that could potentially bias the outcomes, and the fact that men in the two groups may have received different treatments for prostate cancer.

Another limitation was that the reason why men were tested at baseline for PSA was not available in the Northern Ireland data. Available evidence indicates, however, that less than 20 percent of PSA tests in this group were in asymptomatic men, while in the ERSPC study presumably almost all of the baseline PSA readings were in asymptomatic men, explained Dr. Eric J. (Rocky) Feuer, chief of the Statistical Research and Applications Branch in NCI’s Division of Cancer Control and Population Sciences.

“The authors indicate that it remains unknown whether men with a specific age and PSA level in a screening population compare equally to men with the same age and PSA in the selected clinical population,” he said. “It is difficult to know to what extent these potential biases could have influenced the overall results of the study.”

The researchers at Erasmus University Medical Center stressed that longer follow-up is needed before clinical recommendations can be made.

Hospitalization Near Death May Diminish Mental Health of Caregivers and Quality of Life for Cancer Patients

Bereaved caregivers of terminally ill cancer patients who died in hospitals or intensive care units (ICUs) are at increased risk for developing psychiatric problems compared with caregivers of patients who died at home, according to a study published online September 13 in the Journal of Clinical Oncology.

The prospective study of 333 dying cancer patients and their closest caregivers—led by Dr. Alexi A. Wright and colleagues at Dana-Farber Cancer Institute, Harvard Medical School, and Brigham and Women’s Hospital—was designed to determine principally whether the place of death for patients with cancer was associated with the patients’ quality of life at the end of life, and also whether it was linked with increased risk for bereavement-related psychiatric disorders in their caregivers.

The researchers reported that caregivers of patients who died in ICUs had an increased risk of developing post-traumatic stress disorder (PTSD) compared with caregivers of patients who died at home with hospice care: 21.1 percent compared with 4.4 percent. “To our knowledge, this is the first study to show that caregivers of patients who die in ICUs are at a heightened risk for developing PTSD,” they wrote. In addition, caregivers of patients who died in the hospital had higher odds of suffering prolonged grief disorder: 21.6 percent compared with 5.2 percent among caregivers of patients who died with home hospice.

Quality of life for the patients was evaluated through reports from their caregivers within 2 weeks of death. The caregiver reports for patients who died in an ICU or hospital revealed more physical and emotional distress and lower quality of life at the end of life, compared with caregiver reports for patients who died at home with hospice services.

Surprisingly, the researchers found that home death was associated with better quality-of-life outcomes compared with outcomes for those who died in the hospital, regardless of whether the patients received hospice services at home.

“Future research is needed to determine why home deaths result in better [quality of life] for patients, but we expect that it may be due to differences in the focus of care provided,” the researchers wrote. “Hospital—and especially ICU—care often focuses on keeping patients alive at all costs, whereas home deaths may emphasize patients’ [quality of life] and symptom management.”

Home death may also improve caregiver outcomes by providing an opportunity for caregivers to deal with the approaching loss and receive support from their community in a familiar environment, they noted.

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