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:

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, California.

Elevated interleukin-12 is a plasma marker of poor prognosis in stage III melanoma patients:

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:

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.

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If lung cancer and heart disease aren’t bad enough, cigarette smokers are also at higher risk for developing, among other things, pancreatic cancer. Now, researchers at the Kimmel Cancer Center at Jefferson in Philadelphia have preliminary evidence indicating one possible reason why. Data being presented April 13, 2008 during the Annual Meeting of the American Association for Cancer Research shows that they have found that nicotine in cigarettes increases the production of a protein that is known to promote cancer cell survival, invasion and spread.

According to Hwyda Arafat, M.D., Ph.D., associate professor of Surgery at Jefferson Medical College of Thomas Jefferson University, the protein, osteopontin, is found in a variety of fluids in the body, such as plasma, cerebrospinal fluid, synovial fluid and breast milk. Osteopontin is also present in different organs and plays an important role during embryonic development. Recent studies have demonstrated that osteopontin levels are significantly higher in the blood and pancreas tissue of pancreatic cancer patients. The protein, when over-produced, can make cancer cells more likely to become metastatic.

Dr. Arafat wanted to see if osteopontin might play a role in the cigarette smoking-pancreatic cancer connection. In collaboration with groups at the University of Nebraska and Rutgers University, Dr. Arafat and her co-workers looked at rats exposed to cigarette smoke and measured the amount of osteopontin in the rat pancreas and blood. They found that the more cigarette smoke to which the rats were exposed, the greater the amount of nicotine in the blood and osteopontin in the pancreas.

The researchers also looked at osteopontin expression in pancreatic cancer cell lines exposed to nicotine, finding that osteopontin expression went up when the cells were exposed to more nicotine. “We found that dose-dependently, nicotine increased osteopontin expression not only through transcriptional but also translational (protein secretion) levels in pancreatic cancer cells,” Dr. Arafat explains. Pancreas tissue samples from pancreatic cancer patients also showed higher than normal levels of the protein.

Dr. Arafat believes that osteopontin could be a drug target. “We are now proposing that perhaps blocking osteopontin can interfere with the progression of pancreatic cancer and other cancers,” she says, adding that her team would like to understand more about osteopontin’s effects on pancreatic cancer cell behavior. Dr. Arafat’s group now is comparing differences in osteopontin expression between smokers and non-smokers.

“For example, if you put the cells with nicotine and block osteopontin, will the cells still be migratory? Is it osteopontin or something else in combination that is at work here?”

Pancreatic cancer, the fourth-leading cause of cancer death in this country, takes some 34,000 lives a year. The disease is difficult to treat; it frequently is detected after it has spread. Only 4 percent of individuals with pancreatic cancer live for five years after diagnosis, and about 25 percent of those who undergo successful surgical removal of their disease live at least that long.

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