Uncovering hypothesis-generating associations between prescription drugs and digestive cancer risk: a case-control drug-wide association study (DWAS).

Abstract

Background: Prescription drug use among older adults is more common than ever, yet traditional trials are not designed to assess long-term outcomes. Thus, the potential impact of widely used medications on cancer risk remains unclear. This is particularly a concern for digestive cancers for several reasons, most notably their key role in drug absorption and metabolism. We therefore leverage large-scale data to conduct a multi-stage study, aimed at identifying potential associations between oral prescription drugs and digestive cancer risk.

Methods: We used the Surveillance, Epidemiology and End Results (SEER)-Medicare data for a case-control drug-wide association study (DWAS), followed by targeted analyses to further address confounding. Subsequent analyses conducted include incorporation of additional adjustment for comorbidities, use of active comparators as well as propensity scores. Associations between prescription drugs and digestive cancer were assessed using adjusted odds ratios (OR), with significance assessed using Benjamini-Yekutieli (BY)-adjusted p-values.

Results: In initial scan, 218 of 442 oral prescription drugs were associated with digestive cancer (BY-adjusted p<0.05). After our multi-stage targeted analyses, 38 drugs of interest (vs. their active comparators) remained associated with digestive cancer. Specifically, 10 drugs were positively associated (OR>1) and 28 were inversely associated (OR<1).

Conclusions: Our study confirms some previously reported associations and identifies additional potential, novel associations between individual oral prescription drugs and digestive cancer that merit additional follow-up.

Impact: These findings support the utility of our approach for hypothesis generation and warrant targeted confirmation in prospective studies as well as investigation of specific cancer types driving these associations.