Aging: How Growing Older Affects Cancer Risk and Outcomes
April 16, 2008
SAN DIEGO - As our population ages and senior citizens become a larger demographic, cancer researchers are focusing on the links between aging and cancer. Studies presented at the 2008 Annual Meeting of the American Association for Cancer Research, April 12 - 16, highlight the biological aspects of aging that are key to greater risk and poorer prognosis, and surgical outcomes.
Surgical resection and survival in octogenarians and younger age cohorts of patients diagnosed with non-small cell lung cancer: Abstract 5537
Although fewer of them undergo surgery, lung cancer patients in their 80s fare equally well following surgery as their younger counterparts, researchers report. The findings offer doctors potentially valuable guidance in treatment options for elderly patients, according to researchers.
A research team from the Hoag Cancer Center in Newport Beach, California, observed 1,293 patients with lung cancer, 482 of whom underwent surgical treatment. The oldest patients were more likely to be male. Older patients were also more likely to have localized disease.
Overall, the rate of surgery did not differ by age group. However, when primary lung cancer was considered separately, only 31.7 percent of patients older than 80 underwent surgery for their primary lung cancer compared with 38.5 percent of patients younger than 80. For patients with non-small cell lung cancer, the rate of surgery was 64 percent for those older than 80 and 83 percent for those younger than 80. For patients with regionally advanced disease, the rate of surgery for patients age 80 or older was 35 percent compared with 49 percent for those younger than 80 years old.
The five-year survival rate following surgery was 62 percent for those patients older than 80 compared with 53 percent for those aged 70 to 79 years. Among patients age 60 to 69 years and 50 to 59 years, the survival rate was 63 percent. For the youngest patients, those younger than 50, the survival rate was 79 percent.
"Although a smaller proportion of patients over the age of 80 underwent this type of surgery, their survival rate was comparable to the younger age groups," said lead author Robert O. Dillman, M.D., medical director of the Hoag Cancer Center in Newport Beach,
Elevated interleukin-12 is a plasma marker of poor prognosis in stage III melanoma patients: Abstract 5568
New research has established that elevated blood levels of interleukin-12, which rise as we age, independently predicts poor prognosis in patients with melanoma.
Interleukin-12 is a biological therapeutic agent that has been shown to act on the immune system and increase the body's ability to fight disease. It has also previously been shown to interfere with blood flow to the tumors.
However, the current study suggests that elevated interleukin-12 may play a role in poor prognosis for melanoma.
"This marker tends to increase with age, which could explain the link between age and poorer prognosis of this type of skin cancer," said lead author Yun S. Chun, M.D., a surgical oncology fellow at the University of Texas M. D. Anderson Cancer Center.
Researchers measured blood levels of interleukin-12 in 658 patients. Of these patients, 445 had early stage disease, 150 had mid-stage disease and 63 had late stage disease.
As they predicted, Chun and colleagues found that blood levels of interleukin-12 rose with age. Among patients younger than 40, the average level of interleukin-12 was 75 pg/ml, those aged 40 to 59 had a average level of 84 pg/ml, those from 60 to 79 years had a level of 96 pg/ml and patients older than 80 had an average level of 112 pg/ml.
When researchers estimated risk factors for mortality among patients with melanoma, older age by itself did not predict risk. However, late stage disease and an elevated level of interleukin-12 did predict mortality. Specifically, for patients with late stage disease and an interleukin-12 level above 150 pg/ml, the risk of mortality was four times higher than that for patients with levels of interleukin-12 that were below 150 pg/ml.
"Among patients with melanoma, it is possible that elevated interleukin-12 may be a marker of a tumor promoting, rather than a tumor inhibiting, response," Chun said.
Aging and DNA methylation in Alu and LINE-1 repeated elements: Abstract 557
An age-related decrease in DNA methylation, the process whereby genes are shut off and chromosomes packed up in complex strictures, could potentially lead to cancer development, according to researchers.
When a person does not have a proper rate of DNA methylation, chromosomes and DNA sequences become unstable, and therefore are more likely to contribute to cancer.
Approximately 55 percent of the human genome consists of repetitive elements, including approximately 500,000 long interspersed nucleotide elements (LINE) and 1.5 million repetitive elements of the Alu DNA sequences. Typically, these sequences undergo heavy methylation.
Previous human studies have linked a lack of methylation among LINE and Alu repetitive elements with disease. However, whether the unsteadiness of these elements is unrestrained with age had not yet been established.
For the current study, researchers from the Center of Molecular and Genetic Epidemiology at the University of Milan in Italy, in collaboration with investigators at the Harvard School of Public Health, Boston, MAmeasured DNA levels in 693 patients. Patients gave up to three blood samples, taken approximately three years apart from each other.
Overall, the older a patient grew, the less likely these elements were to methylate. Specifically, researchers found a 0.016 percent decrease for LINE-1 elements and a 0.015 percent decrease for Alu repetitive elements for each year of increased age.
"Such age-related decrease in methylation may increase the risk of mutational events potentially leading to cancer," said lead author Laura Cantone, a researcher at the University of Milan.
# # #
The mission of the American Association for Cancer Research is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 27,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication and its sixth major journal, Cancer Prevention Research, is the only journal worldwide dedicated exclusively to cancer prevention, from preclinical research to clinical trials. The AACR also publishes CR, a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. CR provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.
Staci Vernick Goldberg
In San Diego (4/12-4/16):