Researchers present colon-cancer findings at AACR meeting

Colon-cancer studies by two Center researchers were among those presented to the media during the 100th Annual Meeting of the American Association for Cancer Research in Denver April 18-22. Andrea Burnett-Hartman, a doctoral student in the Public Health Sciences Division, discussed her findings about the role of smoking and consumption of charred red meat on the development of certain colon polyps. Findings were also presented from Dr. Cornelia (Neli) Ulrich's study of patients who might benefit from cox-2 inhibitor therapy to reduce the risk of colon cancer.

Burnett-Hartman study: Smoking increases risk of colon polyps
Burnett-Hartman and colleagues studied the risk of hyperplastic polyps and adenomas associated with cigarette smoking, charred red-meat intake and variations in the mEH gene; a gene responsible for processing some of the carcinogens found in cigarette smoke and charred meat. Although both adenomas and hyperplastic polyps had elevated risks associated with cigarette smoking, the association for hyperplastic polyps was stronger than for adenomas.

Researchers recruited 529 patients with adenoma, 691 patients with hyperplastic polyps, 227 patients with adenomas and hyperplastic polyps, and 772 healthy control patients. These patients were asked a variety of lifestyle questions using a questionnaire and analyses were performed.

If a patient had smoked at least 22 pack-years (one pack-year is equal to smoking one pack per day for one year), the risk of adenomas increased by 68 percent while the risk of hyperplastic polyps increased 2.38-fold. For current smoking status, the risk increase was also 68 percent for adenomas; while the risk of hyperplastic polyps increased 3.02-fold.

Frequency of charred red meat consumption was consistently associated with slightly elevated risks in all polyp groups, but this association was not significant. Also, there was no link between polyps of any type and variation in the mEH gene.

"Colon cancer has a very strong environmental component, but based on the results of our study, these common gene variants do not significantly protect an individual from the carcinogenic effect of smoking," said Burnett-Hartman.
 
Ulrich study links single nucleotide polymorphism to reduced colorectal-cancer risk
Since Merck voluntarily recalled Vioxx in 2004, clinicians have been reluctant to use the remaining COX2 inhibitors on the market due to their risk of cardiovascular side effects. Nevertheless, COX2 inhibitors, and nonsteroidal drugs in general (including ibuprofen and aspirin), have a proven efficacy against developing colorectal cancer, the number two cause of cancer deaths among men and women. Thus, researchers are working to identify patients whose benefit might be high enough to outweigh the risk of cardiovascular disease.

Ulrich, of the Cancer Prevention Program in PHS, has identified a single nucleotide polymorphism (SNP) that may predict who is at greater risk for colon cancer. SNPs are small genetic changes unique to individuals.

Ulrich and colleagues analyzed data from 2,465 sibling pairs in the Colon Cancer Family Registry and identified 17 COX1 and 13 COX2 tag SNPs. They found that the presence of COX2 rs4648261 was linked with a reduction in colorectal-cancer risk of between 40 percent to 68 percent. No other SNP was associated with reduced risk. Furthermore, characterizing patients by two SNPs in COX2 suggested that only a subset of patients would derive benefit from NSAID use.

Ulrich said these findings would need to be replicated in larger studies before making clinical recommendations, but this was an important first step.

"Non-steroidal anti-inflammatory drugs have been clearly shown to reduce colorectal-cancer risk, but not without their own side effects," said Ulrich. "If we can identify which patients are going to benefit from these drugs, we can more effectively target prevention."
 
Anna Coghill, a graduate research assistant, presented data from the Ulrich study at the press conference.

[Adapted from a news release from the American Association for Cancer Research.]