Analysis of large epidemiologic studies identifies rare variants associated with no preventive benefit

An analysis of genetic and lifestyle data from 10 large epidemiologic studies confirmed that regular use of aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs) appears to reduce the risk of colorectal cancer in most individuals. The study being published in the March 17 issue of JAMA found that a few individuals with rare genetic variants do not share this benefit. The study authors note, however, that additional questions need to be answered before preventive treatment with these medications can be recommended for anyone.

"Previous studies, including randomized trials, demonstrated that NSAIDS, particularly aspirin, protect against the development of colorectal cancer, but it remains unclear whether an individual's genetic makeup might influence that benefit," says Andrew Chan, MD, MPH, of the Massachusetts General Hospital (MGH) Gastroenterology Division, co-senior and co-corresponding author of the JAMA report. "Since these drugs are known to have serious side effects - especially gastrointestinal bleeding - determining whether certain subsets of the population might not benefit is important for our ability to tailor recommendations for individual patients."

The research team analyzed data from the Colon Cancer Family Registry and from nine studies included in the Genetics and Epidemiology of Colorectal Cancer Consortium - which includes the Nurses' Health Study, the Health Professionals Follow-up Study and the Women's Health Initiative - comparing genetic data for 8,624 individuals who developed colorectal cancer with that of 8,553 individuals who did not, matched for factors such as age and gender. The comprehensive information on lifestyle and general health data provided by participants in the studies again confirmed that regular use of aspirin or NSAIDs was associated with a 30 percent reduction in colorectal cancer risk for most individuals. However, that preventive benefit did not apply to everyone, and the study found no risk reduction in participants with relatively uncommon variants in genes on chromosome 12 and chromosome 15.

"Determining whether an individual should adopt this preventive strategy is complicated, and currently the decision needs to balance one's personal risk for cancer against concerns about internal bleeding and other side effects," states Chan, who is an associate professor of Medicine at Harvard Medical School. "This study suggests that adding information about one's genetic profile might help in making that decision. However, it is premature to recommend genetic screening to guide clinical care, since our findings need to be validated in other populations. An equally important question that also needs to be investigated is whether there are genetic influences on the likelihood that someone might be harmed by treatment with aspirin and NSAIDs."

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The lead author of the JAMA report is Hongmei Nan, MD, PhD; formerly a research fellow at Brigham and Women's Hospital and now on the faculty at the Fairbanks School of Public Health and the Simon Cancer Center at Indiana University. Li Hsu, PhD, of the Fred Hutchinson Cancer Research Center is co-corresponding author, and Ulrike Peters, PhD, MPH, also of Fred Hutch, is co-senior author. Support for this study includes several grants from the National Cancer Institute and the National Institute for Diabetes and Digestive and Kidney Diseases.

Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $760 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, reproductive biology, systems biology, transplantation biology and photomedicine.

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Genetic background determines whether aspirin/NSAIDS will reduce colorectal cancer risk