Dataset Information

Exploratory Genome-Wide Interaction Analysis of Nonsteroidal Anti-inflammatory Drugs and Predicted Gene Expression on Colorectal Cancer Risk.

ABSTRACT:

Background

Regular use of nonsteroidal anti-inflammatory drugs (NSAID) is associated with lower risk of colorectal cancer. Genome-wide interaction analysis on single variants (G × E) has identified several SNPs that may interact with NSAIDs to confer colorectal cancer risk, but variations in gene expression levels may also modify the effect of NSAID use. Therefore, we tested interactions between NSAID use and predicted gene expression levels in relation to colorectal cancer risk.

Methods

Genetically predicted gene expressions were tested for interaction with NSAID use on colorectal cancer risk among 19,258 colorectal cancer cases and 18,597 controls from 21 observational studies. A Mixed Score Test for Interactions (MiSTi) approach was used to jointly assess G × E effects which are modeled via fixed interaction effects of the weighted burden within each gene set (burden) and residual G × E effects (variance). A false discovery rate (FDR) at 0.2 was applied to correct for multiple testing.

Results

Among the 4,840 genes tested, genetically predicted expression levels of four genes modified the effect of any NSAID use on colorectal cancer risk, including DPP10 (P_G×E = 1.96 × 10^-4), KRT16 (P_G×E = 2.3 × 10^-4), CD14 (P_G×E = 9.38 × 10^-4), and CYP27A1 (P_G×E = 1.44 × 10^-3). There was a significant interaction between expression level of RP11-89N17 and regular use of aspirin only on colorectal cancer risk (P_G×E = 3.23 × 10^-5). No interactions were observed between predicted gene expression and nonaspirin NSAID use at FDR < 0.2.

Conclusions

By incorporating functional information, we discovered several novel genes that interacted with NSAID use.

Impact

These findings provide preliminary support that could help understand the chemopreventive mechanisms of NSAIDs on colorectal cancer.

SUBMITTER: Wang X

PROVIDER: S-EPMC7556991 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Publications

Exploratory Genome-Wide Interaction Analysis of Nonsteroidal Anti-inflammatory Drugs and Predicted Gene Expression on Colorectal Cancer Risk.

Wang Xiaoliang X Su Yu-Ru YR Petersen Paneen S PS Bien Stephanie S Schmit Stephanie L SL Drew David A DA Albanes Demetrius D Berndt Sonja I SI Brenner Hermann H Brenner Hermann H Campbell Peter T PT Casey Graham G Chang-Claude Jenny J Gallinger Steven J SJ Gruber Stephen B SB Haile Robert W RW Harrison Tabitha A TA Hoffmeister Michael M Jacobs Eric J EJ Jenkins Mark A MA Joshi Amit D AD Li Li L Lin Yi Y Lindor Noralane M NM Marchand Loïc Le LL Martin Vicente V Milne Roger R Maclnnis Robert R Moreno Victor V Nan Hongmei H Newcomb Polly A PA Potter John D JD Rennert Gad G Rennert Hedy H Slattery Martha L ML Thibodeau Steve N SN Weinstein Stephanie J SJ Woods Michael O MO Chan Andrew T AT White Emily E Hsu Li L Peters Ulrike U

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20200710 9

<h4>Background</h4>Regular use of nonsteroidal anti-inflammatory drugs (NSAID) is associated with lower risk of colorectal cancer. Genome-wide interaction analysis on single variants (G × E) has identified several SNPs that may interact with NSAIDs to confer colorectal cancer risk, but variations in gene expression levels may also modify the effect of NSAID use. Therefore, we tested interactions between NSAID use and predicted gene expression levels in relation to colorectal cancer risk.<h4>Meth ...[more]

PMID: 32651213

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Project description:Background & aimsNonsteroidal anti-inflammatory drugs (NSAIDs) have been suggested to protect against esophageal adenocarcinoma (EAC). This study examined the effect of NSAIDs on the risk of developing Barrett's esophagus (BE), the precursor lesion to EAC.MethodsWe conducted a case-control study among eligible patients scheduled for either elective esophagogastroduodenoscopy (EGD) or recruited from primary care clinics to undergo a study EGD. We compared 323 patients with BE (296 nondysplastic and 27 dysplastic) with 2 separate control groups: 1347 patients from the elective EGD group (endoscopy controls) and 502 patients from the primary care group (primary care controls) with no endoscopic or histopathologic BE. Use of aspirin products and 23 nonaspirin NSAIDs was ascertained from detailed, self-reported questionnaires. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using multivariable logistic regression models.ResultsThere were no significant differences in self-reported NSAID use between all BE cases and all controls (58.2% vs 54.6%; P = .33); this was seen for aspirin products (43.0% vs 37.4%; P = .08) and nonaspirin NSAIDs (7.7% vs 8.9%; P = .46). These findings persisted in the multivariable model for any NSAIDs (adjusted OR, 0.89; 95% CI, 0.75-1.28), aspirin (adjusted OR, 1.16; 95% CI, 0.90-1.51), and nonaspirin NSAIDs (adjusted OR, 0.88; 95% CI, 0.55-1.39). Use of a combination of aspirin and nonaspirin NSAIDs was reported in 7.4% of cases and 8.3% of controls, and a nonsignificant inverse association with BE was seen (adjusted OR, 0.70; 95% CI, 0.44-1.11). There was no significant association between BE and daily NSAID use (adjusted OR, 1.03; 95% CI, 0.78-1.37). Similar findings were observed for comparisons involving nondysplastic or dysplastic BE cases, and endoscopy or primary care control groups separately or combined.ConclusionsThe use of NSAIDs was not associated with a reduced risk of BE. It is likely that the protective mechanism of NSAIDs on EAC occurs subsequent to the development of BE.

Dataset Information

Exploratory Genome-Wide Interaction Analysis of Nonsteroidal Anti-inflammatory Drugs and Predicted Gene Expression on Colorectal Cancer Risk.

Background

Methods

Results

Conclusions

Impact

Publications

Exploratory Genome-Wide Interaction Analysis of Nonsteroidal Anti-inflammatory Drugs and Predicted Gene Expression on Colorectal Cancer Risk.

Similar Datasets

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