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Effects of long-term aspirin use on molecular alterations in precancerous gastric mucosa in patients with and without gastric cancer.

ABSTRACT: The risk of gastric cancer (GC) remains even after H. pylori eradication; thus, other combination treatments, such as chemopreventive drugs, are needed. We evaluated the effects of aspirin on genetic/epigenetic alterations in precancerous conditions, i.e., atrophic mucosa (AM) and intestinal metaplasia (IM), in patients with chronic gastritis who had taken aspirin for more than 3 years. A total of 221 biopsy specimens from 74 patients, including atrophic gastritis (AG) cases without aspirin use (control), AG cases with aspirin use (AG group), and GC cases with aspirin use (GC group), were analyzed. Aspirin use was associated with a significant reduction of CDH1 methylation in AM (OR: 0.15, 95% CI: 0.06-0.41, p?=?0.0002), but was less effective in reversing the methylation that occurred in IM. Frequent hypermethylation including that of CDH1 in AM increased in the GC group compared to the AG group, and CDH1 methylation was an independent predictive marker of GC (OR: 8.50, 95% CI: 2.64-25.33, p?=?0.0003). In patients with long-term aspirin use, the changes of molecular events in AM but not IM may be an important factor in the reduction of cancer incidence. In addition, methylation of the CDH1 gene in AM may be a surrogate of GC.

SUBMITTER: Michigami Y

PROVIDER: S-EPMC5645329 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Effects of long-term aspirin use on molecular alterations in precancerous gastric mucosa in patients with and without gastric cancer.

Michigami Yuki Y Watari Jiro J Ito Chiyomi C Hara Ken K Yamasaki Takahisa T Kondo Takashi T Kono Tomoaki T Tozawa Katsuyuki K Tomita Toshihiko T Oshima Tadayuki T Fukui Hirokazu H Morimoto Takeshi T Das Kiron M KM Miwa Hiroto H

Scientific reports 20171017 1

The risk of gastric cancer (GC) remains even after H. pylori eradication; thus, other combination treatments, such as chemopreventive drugs, are needed. We evaluated the effects of aspirin on genetic/epigenetic alterations in precancerous conditions, i.e., atrophic mucosa (AM) and intestinal metaplasia (IM), in patients with chronic gastritis who had taken aspirin for more than 3 years. A total of 221 biopsy specimens from 74 patients, including atrophic gastritis (AG) cases without aspirin use ...[more]

PMID: 29042646

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Project description:BackgroundDespite the known role of mitosis in colorectal cancer, previous associations of long-term aspirin use with suppressed cancer-related epigenetic aging did not involve epigenetic mitotic clocks. We investigated these relationships using three epigenetic mitotic clocks developed for cancer risk prediction: EpiTOC, EpiTOC2, and MiAge. We utilized publicly available HumanMethylationEPIC BeadChip data from 112 healthy colon (proximal and distal) mucosal samples taken at baseline (T1) and at 10-years follow-up (T2) from a screening cohort of 28 Polish women (11 non-users and 17 long-term [≥ 2 years] aspirin users). Mitotic clock values were divided by chronological age at each timepoint to obtain intrinsic rates (IRs). We evaluated differences in residuals of the mitotic clock IRs taken from linear mixed effects models adjusted for BMI, polyp status, and DNA methylation batch.FindingsEpiTOC, EpiTOC2 and MiAge were significantly correlated with chronological age (P < 0.05) with correlations ranging from 0.41 to 0.63. The EpiTOC, EpiTOC2 and MiAge clocks were strongly correlated with each other in proximal and distal samples (r > 0.79, P < 0.0001). We observed proximal within group median clock IR deceleration for EpiTOC (-0.0004 DNAm, P = 0.008), EpiTOC2 (-16 cell divisions, P = 0.009), and MiAge (-3 cell divisions, P = 0.002) for long-term aspirin users from T1 to T2 but not for non-users. In distal samples, only the long-term user MiAge IR was significantly deaccelerated (-3 cell divisions, P = 0.009).ConclusionsOur observed findings support previously reported longitudinal associations of aspirin use with deceleration of other epigenetic age measures in the proximal colon. Our mitotic clock results suggest that cell proliferation could play a role in some aspirin relationships with epigenetic aging. Furthermore, the findings provide added impetus for establishing gold standards for epigenetic aging and consensus guidelines for more comprehensive reporting in future epigenetic aging cancer studies.

Project description:BackgroundAlthough aspirin is increasingly utilized to reduce the event of severe perioperative complications, the effect of long-term aspirin use (L-AU) on perioperative complications in patients undergoing shoulder arthroplasty (SA) has not been well studied. The goal of the present study is to identify the influence of L-AU on perioperative complications in individuals undergoing SA.MethodsWe selected data from the National Inpatient Sample database between 2010 and 2019, to identify adult patients with SA. Patients were subsequently categorized into L-AU and whole non-L-AU cohorts according to the presence of aspirin use. The demographic and comorbidity characteristics were matched using propensity score matching (PSM). The Pearson chi-square test, Wilcoxon rank test and logistic regression were utilized to assess the association of L-AU with perioperative complications.ResultsFrom 2010 to 2019, a total of 162,418 SA patients satisfied the inclusion criteria, with 22,659 (13.95%) using aspirin on a long-term basis. The vast majority of the patients with pre-existing L-AU were aged 65-74 years, female, White and had Medicare insurance. L-AU before surgery was linked to increased risks of perioperative complications, such as blood transfusion (adjusted odds ratio [aOR]: 1.339), genitourinary disease (aOR: 1.349), acute renal failure (aOR: 1.292), acute myocardial infarction (aOR: 1.494), higher total charge (L-AU vs. the whole non-L-AU vs. matched non-L-AU: $66,727.15 vs. $59,697.08 vs. $59,926.32), and prolonged hospitalization stay (LOS) (aOR: 0.837). However, L-AU was considered a protective factor of acute cerebrovascular disease (aOR: 0.722) and stroke (aOR: 0.725).ConclusionsOur study is based on the largest open-access all-payer inpatient database, revealing a noteworthy finding of aspirin's protective and adverse impact on different postoperative complications in the US population, such as acute cardiovascular disease, and stroke, etc. Further studies assessing the optimum preoperative aspirin duration and dosage to meet the best benefit quantity for patients with planned joint arthroplasties are suggested.

Dataset Information

Effects of long-term aspirin use on molecular alterations in precancerous gastric mucosa in patients with and without gastric cancer.

Publications

Effects of long-term aspirin use on molecular alterations in precancerous gastric mucosa in patients with and without gastric cancer.

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