Abstract 2159: A prospective study of non-steroidal anti-inflammatory drug use and colorectal adenoma and colorectal cancer
Authors: Huang Wen-Yi , Su L. Joseph , Johnson Christine C. , Purdue Mark P. , Berndt Sonja I. 
Published: May 2015

Background: Use of non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin and ibuprofen, has been shown to yield a chemopreventive effect against colorectal cancer. Whether NSAIDs protect against the initiation vs. the progression of colorectal cancer remains a debate. To explore its role in the course of colorectal carcinogenesis, we evaluated the associations of NSAIDs with incident adenoma, recurrent adenoma, and colorectal cancer in the context of a large population-based screening trial, where participants were randomized to undergo endoscopic examinations in a controlled setting.

Methods: We prospectively evaluated the associations between self-reported baseline NSAIDs use and risk of incident distal adenoma (1,127 cases), recurrent adenoma (755 cases), and colorectal cancer (840 cases) among men and women, ages 55-74, enrolled between 1993-2001, and randomized to receive flexible sigmoidoscopy screening (n=77,445) as part of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. Incident adenoma cases were those with a negative sigmoidoscopy at baseline, but then were found to have adenoma on a follow-up sigmoidoscopy 3 or 5 years later. Recurrent adenoma cases were identified via an ancillary study nested within the PLCO among participants who had an adenoma at baseline and another adenoma on a surveillance colonoscopy 6 months to 10 years after their baseline screen. Participants were followed for cancer incidence for the median of 11.9 years following the baseline screen. All diagnoses of colorectal adenoma and cancer were pathologically confirmed through medical record review. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) for adenoma incidence and recurrence and hazard ratios (HRs) and 95% CIs for colorectal cancer incidence using multivariable-adjusted models.

Results: Compared to no or infrequent use (&lt;4 times/month), we found aspirin use ≥2 times/day to be associated with a reduced risk of incident adenoma (OR=0.72, 95% CI:0.52-1.00). Although not significantly associated with recurrent adenoma (OR=1.00) or colorectal cancer (OR=0.80), a marginally significant dose trend was observed for colorectal cancer (P=0.05). Similarly, ibuprofen use ≥2 times/day was associated with a reduced risk for incident adenoma (OR=0.72, 95% CI:0.54-0.97), but not associated with adenoma recurrence or cancer. No systematic differences in risk patterns were found by anatomic site, i.e., proximal colon, distal colon or rectum.

Conclusion: Our data suggest that use of aspirin and ibuprofen significantly reduces adenoma initiation, but benefit against progression to adenoma recurrence or cancer growth may be weaker. Given the recognized adverse effects of NSAIDs, such as gastric ulcer perforation and upper gastrointestinal bleeding, any chemopreventive recommendations associated with NSAID use need to be tailored by individual cost-benefit assessment.

Citation Format: Wen-Yi Huang, L. Joseph Su, Christine C. Johnson, Mark P. Purdue, Sonja I. Berndt. A prospective study of non-steroidal anti-inflammatory drug use and colorectal adenoma and colorectal cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2159. doi:10.1158/1538-7445.AM2014-2159