Colorectal polyp prevention by daily aspirin use is abrogated among active smokers

Drew, David A.; Goh, Gyuhyeong; Mo, Allen; Grady, James J.; Forouhar, Faripour; Egan, Gretchen; Swede, Helen; Rosenberg, Daniel W.; Stevens, Richard G.; Devers, Thomas J.

doi:10.1007/s10552-015-0686-1

Cited by 20 publications

(14 citation statements)

References 55 publications

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“…Modulation by NSAIDs of DNA adduct formation from passive tobacco smoke has been observed in mice [ 60 ] and an interaction between aspirin and smoking has also been observed in the colon, where reduction of incidence of polyps by daily aspirin use has been shown to be abrogated in active smokers [ 61 ]. While smoking rates in the general United States population have decreased over the past 35 years [ 62 ], the incidence of EA has increased [ 63 , 64 ], suggesting that while tobacco exposure is a risk factor for EA [ 59 , 65 ], the effect of smoking is only one factor in the complex environment to which the BE tissue is exposed.…”

Section: Discussionmentioning

confidence: 99%

NSAID use and somatic exomic mutations in Barrett’s esophagus

et al. 2018

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BackgroundUse of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) has been shown to protect against tetraploidy, aneuploidy, and chromosomal alterations in the metaplastic condition Barrett’s esophagus (BE) and to lower the incidence and mortality of esophageal adenocarcinoma (EA). The esophagus is exposed to both intrinsic and extrinsic mutagens resulting from gastric reflux, chronic inflammation, and exposure to environmental carcinogens such as those found in cigarettes. Here we test the hypothesis that NSAID use inhibits accumulation of point mutations/indels during somatic genomic evolution in BE.MethodsWhole exome sequences were generated from 82 purified epithelial biopsies and paired blood samples from a cross-sectional study of 41 NSAID users and 41 non-users matched by sex, age, smoking, and continuous time using or not using NSAIDs.ResultsNSAID use reduced overall frequency of point mutations across the spectrum of mutation types, lowered the frequency of mutations even when adjusted for both TP53 mutation and smoking status, and decreased the prevalence of clones with high variant allele frequency. Never smokers who consistently used NSAIDs had fewer point mutations in signature 17, which is commonly found in EA. NSAID users had, on average, a 50% reduction in functional gene mutations in nine cancer-associated pathways and also had less diversity in pathway mutational burden compared to non-users.ConclusionsThese results indicate NSAID use functions to limit overall mutations on which selection can act and supports a model in which specific mutant cell populations survive or expand better in the absence of NSAIDs.Electronic supplementary materialThe online version of this article (10.1186/s13073-018-0520-y) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

NSAID use and somatic exomic mutations in Barrett’s esophagus

et al. 2018

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“…Twelve articles summarising results from one RCT 25 and 11 observational studies 29,30,40,42,44,45,47,50,54,61,62 investigated the risk of SP for individuals taking NSAIDs and/or aspirin, two of which also reported SSA/P risk 29,30 , as outlined in Supplementary Table 1(e). The RCT (which was not included in meta-analyses due to the different study design) demonstrated a significant protective association for right-sided, but not left-sided, SP when taking 81mg or 325mg of aspirin compared with placebo 25 .…”

Section: Medicationsmentioning

confidence: 99%

“…There was low heterogeneity and little evidence of publication bias for NSAID (P = 0.43) or aspirin analyses (P = 0.47). One study also reported a null association between SP risk and statin use 50 .…”

Section: Medicationsmentioning

confidence: 99%

Lifestyle Risk Factors for Serrated Colorectal Polyps: A Systematic Review and Meta-analysis

Bailie¹,

Loughrey²,

Coleman³

2017

Gastroenterology

135

127

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“…This incomplete mediation suggests that additional studies focused on identifying additional markers of synchronous CRC risk are warranted; especially those that may influence serrated carcinogenesis. However, the link between smoking and traditional dysplastic adenoma incidence established by other studies suggests that these lesions may also contribute to multifocal tumor development (42, 44, 45). Thus, examination of the genetic markers associated with traditional carcinogenesis (e.g.…”

Section: Discussionmentioning

confidence: 99%

A Prospective Study of Smoking and Risk of Synchronous Colorectal Cancers

Drew

Nishihara

Lochhead

et al. 2017

American Journal of Gastroenterology

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Objective Cigarette smoking has been linked to somatic genetic and epigenetic aberrations, including CpG island methylator phenotype (CIMP)-high, microsatellite instability (MSI)-high, and BRAF mutation. These molecular features have been associated with synchronous primary colorectal cancers (CRCs). Thus, we examined the hypothesis that smoking might be associated with the risk of synchronous CRCs. Design Within the Health Professionals Follow-up Study and Nurses’ Health Study, we examined the relationship of smoking and incidence of CRC according to tumor synchronicity, using duplication-method Cox proportional hazards regression analysis. Results We confirmed 1,981 solitary CRC and 45 synchronous CRC cases during follow up of 134,305 individuals. CRC risk associated with smoking differed significantly by tumor synchronicity status (Pheterogeneity<0.001). When comparing current smokers with never smokers, multivariable hazard ratios (HR) were 5.27 (95% confidence interval [CI], 2.08–13.40) for synchronous CRCs and 0.97 (95% CI, 0.83–1.14) for solitary CRC. Similarly, differential associations were observed when examining cumulative pack-years smoked (Pheterogeneity=0.006). Smoking cessation for ≥10 years relative to current smoking might reduce the risk of synchronous CRCs (multivariable HR=0.42; 95% CI, 0.19–0.95), but not solitary CRC (multivariable HR=1.10; 95% CI, 0.94–1.29)(Pheterogeneity=0.001). Comparing current and former smokers with never smokers, multivariable HRs for synchronous CRCs were significantly higher than those of solitary CRC positive for either CIMP-high, MSI-high, or BRAF mutation (Pheterogeneity=0.002). Conclusion Smoking is associated with an elevated risk of synchronous CRCs. Our data support a model where smoking contributes to an etiologic field effect that favors these somatic molecular alterations and the development of multiple primary tumors.

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Colorectal polyp prevention by daily aspirin use is abrogated among active smokers

Cited by 20 publications

References 55 publications

NSAID use and somatic exomic mutations in Barrett’s esophagus

NSAID use and somatic exomic mutations in Barrett’s esophagus

Lifestyle Risk Factors for Serrated Colorectal Polyps: A Systematic Review and Meta-analysis

A Prospective Study of Smoking and Risk of Synchronous Colorectal Cancers

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