Abstract A60: Use of statin medications and reduced risk of esophageal adenocarcinoma in persons with Barrett's esophagus
Authors: Kantor Elizabeth D. , Onstad Lynn , Blount Patricia L. , Reid Brian J. , Vaughan Thomas L. 
Published: January 2011

Background: The incidence of esophageal adenocarcinoma (EA) has increased dramatically in many developed countries over the past 30 years, with little improvement in its rapid mortality. Persons with the metaplastic condition, Barrett's esophagus (BE), experience increased risk of EA; they are typically followed in surveillance programs to facilitate early diagnosis of cancer, and may therefore benefit from safe and effective chemopreventive agents. Non-steroidal anti-inflammatory drugs (NSAID) have received much attention due to the fact that NSAID use seems to be negatively associated with the development of various cancers, including EA. However, concern over the potential toxicities associated with NSAID use highlights the importance of identifying alternative agents. The general class of statin medications (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) have received recent attention for their potential chemopreventive properties in human and animal studies, but little is known on the possible effects of statin use on the development of EA.

Methods: We assessed the association between statin use and risk of progression to EA in a prospective cohort study of 411 persons with BE followed for a total of 33,656 person-months between 1995 and 2009. Data on use of medications, cigarette smoking, anthropometry and other potential risk factors were collected at baseline through personal interviews and updated over the course of follow-up. Proportional hazards regression was used to calculate the hazard ratios (HR) for NSAID and statin use, while adjusting as necessary for the effects of age, sex, cigarette use, and waist-to-hip ratio.

Results: Overall, 14% of participants reported statin use at baseline, with 40% reporting use on at least one follow-up visit. NSAID use was more common, with 41% of the cohort reporting regular NSAID use at baseline and 70% reporting regular use on at least one follow-up visit. The main analyses focused on the 396 persons with at least 5 months of follow up (median 79.5 months; range 5.7 −170.7 months). The HR for statin use, entered into models as a time-varying covariate, was 0.59 (95% CI=0.26-1.33) when adjusted for age, sex, and smoking history; when NSAID use was added to the model, the HR weakened slightly to 0.68 (95% CI=0.30-1.55). Among persons with high-grade dysplasia, the HR for association between statin use and EA was 0.45 (95%CI=0.15, 1.29). Among persons with high-grade dysplasia, analyses of the joint associations between statins and NSAID was consistent with a multiplicative relationship, with an estimated HR of 0.19 (95%CI=0.06-0.65) comparing persons using both medications to those using neither.

Conclusions: While reduced risks of EA that we observed among statin users may be explained by chance, the point estimates are similar in magnitude to those previously reported for NSAID use in this cohort, and are unlikely to be confounded by known risk factors. Among those with highgrade dysplasia at baseline, there is a suggestion that concurrent use of NSAID and statins is more protective than taking NSAID or statins individually. Continued study of this issue in this and other cohorts is warranted.

Citation Information: Cancer Prev Res 2010;3(12 Suppl):A60.