Researchers make headway in personalized prevention by gaining a better understanding of an individual’s risk for disease development.
DENVER—Candidate genes and epigenetics are key components in the effort to develop and deploy personalized cancer prevention and treatment. Several studies at AACR 2009 took a closer look at both those research pathways.
“There are those of us who believe that prevention is better than trying to identify drugs for treatment after a person has cancer,” said Peter Shields, MD, deputy director of the Lombardi Comprehensive Cancer Center at Georgetown University in Washington, DC. “Today we are talking about personalized medicine in the context of personalized prevention. We are getting closer to understanding the individual risks for cancer that may be developing.”
Meanwhile, “epigenetics is massive,” said Owen O’Connor, MD, PhD. “Epigenetics is this idea that we can turn genes on and turn genes off using histone deacetylase inhibitors (to cause hypomethylation).” Dr. O’Connor is an associate professor of medicine at New York’s Herbert Irving Comprehensive Cancer Center, New York Presbyterian Hospital, and Columbia University Medical Center.
Researchers at Fred Hutchinson Cancer Research Center in Seattle investigated if eating charred red meat and cigarette smoking had different effects on people who had polymorphisms of the mEH gene, which is linked to metabolism of carcinogens (abstract 2116). Both are believed to be related to development of colon cancer.
Andrea N. Burnett-Hartman, MPH, and colleagues queried 529 patients with adenoma, 691 patients with hyperplastic polyps, 227 patients with adenomas and hyperplastic polyps, and 772 healthy control patients regarding lifestyle.
She said that eating charred meat appears to increase risk of colon cancer, but that increase does not reach statistical significance whether the individual eats meat more than three times a week or has favorable or unfavorable genetics.
Smoking cigarettes, on the other hand—especially if the individual has a personal smoking history that exceeds 22 pack-years of consumption—results in a 65% increased risk of developing adenomas and a 2.38-fold risk of developing hyperplastic lesions.
“Even having favorable genetics is not going to protect you from the carcinogenic effects of smoking,” said Ms. Burnett-Hartman, who is a doctoral candidate at the University of Washington. Another group at Hutchinson Center looked at relationships between colon cancer and certain COX1 and COX2 polymorphisms.
Anna Coghill, MPH, and colleagues identified 17 COX1 and 13 COX2 tag single nucleotide polymorphisms. Ms. Coghill said that COX2 rs4648261 was linked with a reduction in colorectal cancer risk of between 40% and 68%. No other single nucleotide polymorphism studied among the 1,584 cases and 2,516 siblings in the Colon Cancer Family Registry appears to have any influence in the risk of developing colon cancer, she said (abstract 2115).
“If we can identify which patients are going to benefit from these drugs, we can more effectively target prevention,” said Ms. Coghill, who is a graduate research assistant. The group was led by Cornelia Ulrich, PhD.
For example, there appears to be a benefit in treatment with COX2 inhibitors such as rofecoxib(Drug information on rofecoxib) (Vioxx) or nonsteroidal anti-inflammatory drugs such as ibuprofen(Drug information on ibuprofen) or aspirin(Drug information on aspirin). But some of these drugs appear to raise heart disease risk, she said.