After a 13-year follow-up, researchers found an association between aspirin and ibuprofen use and distal adenoma, recurrent adenoma and colorectal cancer.
As colorectal cancer continues to be the second highest cause of cancer-related deaths in the U.S., researchers have had a growing interest in prevention strategies. Most recently, the United States Preventive Services Task Force lowered the recommended age for colorectal cancer screenings from 50 to 45.
One potential preventative strategy may be the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and ibuprofen, which were associated with reduced risk of advanced recurrent adenoma (a benign tumor that could progress to cancer) and colorectal cancer. These findings were published in Cancer.
“Chronic inflammation has been implicated in the process of colorectal tumorigenesis, and nonsteroidal anti-inflammatory drugs (NSAIDs) have been identified in preclinical and clinical studies to have a protective effect against colorectal tumors,” the study authors wrote.
The mechanism in which NSAIDs prevent tumor growth is not entirely understood, but may be related to inhibition of the cyclooxygenase enzyme.
Although prior studies have shown reduction in colorectal cancer risk with aspirin use, few evaluated non-aspirin NSAIDs such as ibuprofen and most have grouped all NSAIDs together, the authors noted. The long-term benefit has also been unclear.
To better understand the association of aspirin and ibuprofen with colorectal cancer and adenoma incidence and recurrence, the researchers enrolled 127,454 eligible patients between ages 55 and 74 at 10 sites across the U.S. between 1993 and 2001 who were also participants in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.
Participants completed a self-administered risk factor questionnaire collecting information on demographics, medical history and medication use (including NSAIDs). There were 77,447 participants randomized to an intervention group that was screened for colorectal cancer with flexible sigmoidoscopy at baseline (39,442 of which had a second sigmoidoscopy at the third or fifth year after enrollment). Both groups were actively monitored for cancer incidence through 2011, after which data collection was transitioned to follow-up at a centralized data center and cancer registry linkage (19,000 participants declined further follow-up).
The participants who completed the baseline questionnaire had information on NSAID use and no history of Crohn’s disease, ulcerative colitis, familial polyposis or Gardner’s syndrome.
Among the eligible patients, who had an average age of 63 years, 50.8% were male, 88% were non-Hispanic White, 10% had a family history of colorectal cancer, 10.9% were current smokers and 39% did not regularly use NSAIDs (32% had regular use of aspirin only and 12% of ibuprofen only; 17% had regular use of both).
In the participants who had a negative baseline screen and an adequate third/fifth year screen, cases of incident adenoma occurred more frequently in men, those with a family history of colorectal cancer, current or former smokers and those who received less than three hours of physical activity per week.
For the participants who had adenoma at baseline, recurrent adenoma cases were more frequent in men or non-White patients.
Both regular use of ibuprofen and combined regular use of aspirin and ibuprofen were associated with a significant reduction in risk of the incidence of distal colorectal adenoma overall, with a greater benefit associated for advanced adenoma and no significant protection for nonadvanced adenoma. While there was no evidence of an association between aspirin use and the risk of distal colorectal adenoma overall, there was evidence of a trend between increased aspirin use and reduced risk of advanced adenoma.
The researchers found no significant association between the use of aspirin and the risk of recurrent adenoma overall but did observe a significant association between both aspirin use alone and combined use of aspirin and ibuprofen and a reduced risk of advanced recurrent adenoma (with no benefit observed for nonadvanced recurrent adenoma). There were no significant associations between ibuprofen use alone and risk of recurrent adenoma.
In terms of colorectal cancer incidence, the researchers saw a decrease in the risk overall with increased use of aspirin, ibuprofen and combined use of both. There was a significant inverse association between both aspirin use alone and combined use of aspirin and ibuprofen with cancers in the proximal and distal colon. Ibuprofen use alone was associated with a decreased risk of cancer in the proximal colon but not the distal colon.
“To our knowledge, this is one of the first studies to prospectively evaluate the impact of NSAIDs across the stages of colorectal tumorigenesis in the context of a colorectal cancer screening trial with long-term follow-up,” the authors wrote.
To conclude, the authors noted that further research is necessary to balance the potential for medication-related side effects and life expectancy when assessing the use of NSAIDs for chemoprevention recommendations.
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