Long-term Aspirin Use Research Articles

Risk of gastrointestinal bleeding and benefit from colorectal cancer reduction from long-term use of low-dose aspirin: A retrospective study of 612509 patients.

Aspirin, commonly used for prevention of cardiovascular and cerebrovascular diseases, is well known to protect against development of colorectal cancer (CRC) but increases risk of gastrointestinal bleeding (GIB). This cohort study aims to evaluate the benefit of low-dose aspirin to prevent CRC and its associated risk of GIB. A population-based dataset was used to compare incidence and mortality of CRC and GIB among patients receiving low-dose aspirin with sex-matched and age-matched controls (1:2). A total of 204170 aspirin users taking aspirin for at least 6months and 408339 nonusers were analyzed. Patients' clinical outcomes were documented for up to 14years or until death. A total of 612509 patients were included; 5118 (2.51%) out of 204170 aspirin users were diagnosed with CRC; and 2073 (1.02%) died of the malignancy. On the other hand, 13336 (3.27%) out of 408339 non-aspirin users were diagnosed with CRC, and 6953 (1.70%) died. Using the competing risk regression, aspirin usage significantly reduced CRC mortality (subdistribution hazard ratio=0.59; 95% confidence interval=0.56 to 0.62). A total of 9483 (4.64%) aspirin users developed GIB, and 820 (0.40%) died, while 11198 (2.74%) nonusers developed GIB, and 1488 (0.36%) died. Aspirin usage marginally increased risk of bleeding-related mortality (subdistribution hazard ratio=1.09; 95% confidence interval=1.00 to 1.19). Subgroup analyses showed the use of acid-secreting agents significantly reduced aspirin-induced mortality. The long-term use of aspirin reduces both incidence and mortality of CRC and at the same time increases incidence and mortality risk of GIB. With combination use of acid-secreting agents, the bleeding risk can be reduced.

Aspirin acts in esophageal cancer: a brief review

Improved survival in esophageal cancer patients with regular aspirin use have been reported. However, with conflicting experimental results existed, an explicit definition on the role of aspirin as an adjuvant chemotherapy of esophageal cancer remains unestablished. We have summarized the current epidemiologic trials evidence over antitumor effect of aspirin in esophageal cancer in the past decades, and most of the clinical data supports that long-term regular aspirin use could reduce the mortality and improve the survival in patients with esophageal cancer. Although most of the clinical trials of aspirin on esophageal cancer are designed focusing on the prediagnosed chemo-preventive role, other than the post-diagnosed therapeutic role, it has been suggested by some studies that aspirin use as an adjuvant treatment after the standard surgery in esophageal cancer may benefit more. In the meanwhile, post diagnosed aspirin use may lead to lower risk of hemorrhage and other side effects of NSAIDs. Potential involved molecular pathways in the antitumor activities of aspirin are under studied worldwide for years and the possible mechanisms so far are reviewed in this article as cyclooxygenase (COX)-dependent pathways and COX-independent pathways, involving anti-inflammatory activity, apoptosis, platelet deactivation, PIK3CA mutation specificity and heparanase-related microenvironment changes of tumor cells. NOSH-aspirin has been developed as a succedaneum of aspirin with a wider application ranges by reducing the risk of hemorrhage in aspirin users. Further clinical and basic studies are suggested focusing on whether regular aspirin use as an adjuvant treatment prolongs survival and prevents recurrence in patients with esophageal cancer.

The association of aspirin use with severity of acute exacerbation of chronic obstructive pulmonary disease: a retrospective cohort study

Little is known about the effect of long-term aspirin use on acute severity of COPD. We hypothesized that, in patients hospitalized for acute exacerbation of COPD (AECOPD), long-term aspirin use is associated with lower risks of disease severity (in-hospital death, mechanical ventilation use, and hospital length-of-stay). We conducted a retrospective cohort study using large population-based data from 2012 through 2013. Among 206,686 patients (aged ≥40 years) hospitalized for AECOPD, aspirin users had lower in-hospital mortality (1.0 vs. 1.4%; OR 0.60 [95% CI 0.50–0.72]; P < 0.001) and lower risk of invasive mechanical ventilation use (1.7 vs. 2.6%; OR 0.64 [95% CI 0.55–0.73]; P < 0.001) compared to non-users, while there was no significant difference in risks of non-invasive positive pressure ventilation use. Length-of-stay was shorter in aspirin users compared to non-users (P < 0.001). In sum, in patients with AECOPD, aspirin use was associated with lower rates of in-hospital mortality and invasive mechanical ventilation use, and shorter length-of-stay.

Abstract TMP98: Aspirin and Anticoagulant Usage on Outcomes After Ruptured Arteriovenous Malformation: A Nationwide Sample Analysis

Title: Aspirin and anticoagulant usage on outcomes after ruptured arteriovenous malformation: a Nationwide Inpatient Sample analysis Background: Recently in nationwide study, neither long-term aspirin nor anticoagulant use were associated with differential mortality or complication rates after aneurysmal subarachnoid hemorrhage however their impact on outcomes of ruptured arteriovenous malformation is unclear. Methods: Data from the Nationwide Inpatient Sample (NIS; 2006–2014) were analyzed in patients with a primary diagnosis of SAH and/or ICH with a diagnosis of an arteriovenous malformation. These patients were divided in two groups: receiving long-term aspirin or anticoagulant use versus neither. Multivariable logistic regression was performed to calculate the adjusted odds of in-hospital mortality, a nonroutine discharge (any discharge other than to home), or a poor outcome (death, discharge to institutional care, tracheostomy, or gastrostomy) for patients with long-term aspirin or anticoagulant use. Multivariable linear regression was used to evaluate length of hospital stay. Covariates included patient demographics, comorbidities, APDRG severity scale, and treatment of AVM including embolization, surgical resection and radiosurgery. Results: Our study examined 11066 patients with ruptured AVM. Patients taking either aspirin (2.5 %, n =273) or anticoagulation (1.7 %, n =185) were significantly older and had a greater burden of comorbid disease (hypertension, hyperlipidemia, atrial fibrillation and renal disease, p &lt; 0.001). Inpatient mortality (10.9 % either aspirin/anticoagulation vs 9.2 % neither, p = 0.63) Length of stay (9.3 ± 8.7 days vs 11.0 ± 13.5 days p = 0.11) were not significantly different. In multivariable logistic regression models for outcome, discharge disposition was better in ASA/Anticoagulation group (home discharge OR 2.36, CI 1.40-3.98, p = 0.001) but inpatient mortality was not different (OR 0.79, CI 0.34-1.82, p=0.58). Conclusion: In this nationwide study, neither long-term aspirin nor anticoagulant use was associated with differential mortality after ruptured arteriovenous malformation. Aspirin/anticoagulant use was associated with favorable discharge to home.

Abstract 174: Preeclampsia and Early Stroke Incidence in the California Teachers Study

Background: Preeclampsia (PEC) occurs in 3-8% of all pregnancies and doubles women’s long-term stroke risk. Prospective data are limited regarding the rate at which this risk develops. We hypothesized that history of PEC would increase risk of early stroke (ES), defined as stroke before age 60 without concurrent PEC, in women in the California Teachers Study (CTS), and that the risk would be modified by aspirin or statin use. Methods: CTS participants aged ≤60 years with no prior stroke at time of enrollment in 1995 were included in this analysis. Baseline characteristics and medical and gynecological history were obtained by serial questionnaires. Participants were followed prospectively and stroke outcomes obtained via linkage with California hospital records through 12/31/2012. Poisson regression was used to calculate relative risk of ES incidence, among those with and without history of PEC, in unadjusted and adjusted models. We used stratified analyses to assess risk of ES in women with and without self-reported use of aspirin and/or statins. Results: Of the 60,817 women included in the analysis, 3734 (6.1%) had PEC. Incident ES occurred in 49 (1.3%) women in the PEC group and 430 (0.8%) in the non-PEC group. Risk of ES incidence was greater in women with PEC compared to non-PEC in unadjusted models (RR 1.7, 95%CI 1.3-2.3). Adjusting for age, hypertension, diabetes, migraine, and obesity, RR remained higher in the PEC group (RR 1.4, 95%CI 1.1-1.9). Stratified analyses showed that this risk was mitigated in women taking aspirin or statins (RR 1.3, 95%CI 0.8-2.1), but elevated in those not taking them (RR 1.5, 95%CI 1.02-2.3). Conclusion: Women with prior PEC were 40% more likely than those without PEC to develop ES, even controlling for other risk factors. Women with a history of PEC should be considered high risk for ES. Randomized trials are needed to assess whether long-term use of aspirin and/or statins would benefit all women with a history of PEC.

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Low-Dose Aspirin Use Does Not Increase Survival in 2 Independent Population-Based Cohorts of Patients With Esophageal or Gastric Cancer

Preclinical studies have shown aspirin to have anticancer properties and epidemiologic studies have associated aspirin use with longer survival times of patients with cancer. We studied 2 large cohorts to determine the association between aspirin use and cancer-specific mortality in patients with esophageal or gastric cancer. We performed a population-based study using cohorts of patients newly diagnosed with esophageal or gastric cancer, identified from cancer registries in England from 1998 through 2012 and the Scottish Cancer Registry from 2009 through 2012. Low-dose aspirin prescriptions were identified from linkages to the United Kingdom Clinical Research Practice Datalink in England and the Prescribing Information System in Scotland. Deaths were identified from linkage to national mortality records, with follow-up until September 2015 in England and January 2015 in Scotland. Time-dependent Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for cancer-specific mortality by low-dose aspirin use after adjusting for potential confounders. Meta-analysis was used to pool results across the 2 cohorts. The combined English and Scottish cohorts contained 4654 patients with esophageal cancer and 3833 patients with gastric cancer, including 3240 and 2392 cancer-specific deaths, respectively. The proportions surviving 1 year, based on cancer-specific mortality, were similar in aspirin users vs non-users after diagnosis with esophageal cancer (48% vs 50% in England and 49% vs 46% in Scotland, respectively) or gastric cancer (58% vs 57% in England and 59% vs 55% in Scotland, respectively). There was no association between postdiagnosis use of low-dose aspirin and cancer-specific mortality among patients with esophageal cancer (pooled adjusted HR, 0.98; 95% CI, 0.89-1.09) or gastric cancer (pooled adjusted HR, 0.96; 95% CI, 0.85-1.08). Long-term aspirin use was not associated with cancer-specific mortality after diagnosis of esophageal cancer (pooled adjusted HR, 1.03; 95% CI, 0.85-1.25) or gastric cancer (pooled adjusted HR, 1.06; 95% CI, 0.85-1.32). In analyses of 2 large independent cohorts in the United Kingdom, low-dose aspirin usage was not associated with increased survival of patients diagnosed with esophageal or gastric cancer.

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

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.

Efficacy and Safety of Proton Pump Inhibitors in the Long-Term Aspirin Users: A Meta-Analysis of Randomized Controlled Trials.

Long-term aspirin use in cardiovascular disease prevention may result in gastrointestinal bleeding. Although proton pump inhibitors (PPI) have been shown to reduce the risks of peptic ulcers and dyspeptic symptoms in long-term aspirin users in the randomized controlled trials, there are safety concerns about the long-term use of PPI. What is the safety and efficacy of PPI in patients using aspirin in long term for prevention of cardiovascular diseases and stroke? We searched MEDLINE, EMBASE, CENTRAL, CINAHL, ProQuest, and relevant references from inception through February 2015, and used random-effects model for meta-analysis. A total of 10 publications from 9 studies (n = 6382) were included in the meta-analysis. Compared with control, PPI reduced the risks of peptic ulcers [risk ratio (RR): 0.19; 95% confidence interval: 0.13-0.26; P < 0.00001], gastric ulcers [0.24 (0.16-0.35); P < 0.00001], duodenal ulcers [0.12 (0.05-0.29); P < 0.00001], bleeding ulcers [0.22 (0.10-0.51); P = 0.0004], and erosive esophagitis [0.14 (0.07-0.28); P < 0.00001]. PPI increased the resolution of epigastric pain [1.13 (1.03-1.25); P = 0.01], heartburn [1.24 (1.18-1.31); P < 0.00001], and regurgitation [1.26 (1.13-1.40); P < 0.0001], but did not increase the risks of all-cause mortality [1.72 (0.61-4.87); P = 0.31], cardiovascular mortality [1.80 (0.59-5.44); P = 0.30], nonfatal myocardial infarction/ischemia [0.56 (0.22-1.41); P = 0.22], ischemic stroke/transient ischemic attack [1.09 (0.34-3.53); P = 0.89] and other adverse events. The PPI seems to be effective in preventing peptic ulcers and erosive esophagitis and in resolution of dyspeptic symptoms without increasing adverse events, cardiac risks or mortality in long-term aspirin users.

Abstract 3012: Long-term aspirin use and total and cancer-specific mortality

Abstract Background: Long-term follow of clinical trials of aspirin for the prevention of cardiovascular disease have shown that aspirin may be associated with a reduced risk of death from cancer, including colorectal, esophageal, and lung cancer, and possibly breast and prostate cancer. However, the potential benefits of aspirin use, at a range of doses and duration of use, on total and cancer-specific mortality have not been examined in large prospective cohort studies with long-term follow-up. Methods: We examined the association between aspirin use and subsequent total and cancer-specific mortality, at a range of doses and duration of use, among 86,206 women in the Nurses' Health Study (1980-2012) and 43,977 men in the Health Professionals Follow-up Study (1986-2012). Participants with a history of cancer, heart disease, or stroke were excluded. Aspirin use was assessed at baseline and updated every 2 years with greater than 90% follow-up. Cox proportional hazards models were used to compute hazard ratios as estimates for age- and multivariable-adjusted relative risks (RRs) and 95% confidence intervals (CIs). Results: During up to 32 years of follow-up, 22,094 women and 14,749 men died, and 8,271 women and 4,591 men died of cancer. Compared with nonregular use, regular aspirin use was associated with lower risk of total mortality (multivariable-adjusted RR 0.93; 95% CI 0.90-0.95 for women and RR 0.89; 95% CI 0.86-0.93 for men), which was primarily due to a lower risk of dying from any cancer (RR 0.93; 95% CI 0.89-0.97 for women and RR 0.85; 95% CI 0.80-0.90 for men), especially colorectal cancers (RR 0.69; 95% CI 0.59-0.81 for women and RR 0.70; 95% CI 0.57-0.85 for men), breast cancers (RR 0.89; 95% CI 0.79-0.99), prostate cancers (RR 0.77; 95% CI 0.65-0.90), and lung cancers in men (RR 0.86; 95% CI 0.74-0.99). The benefit of aspirin on cancer mortality appeared evident with use of at least 0.5 to 1.5 standard aspirin tablets per week for both men and women; and the minimum duration of regular use associated with lower cancer mortality was 6 years. Conclusions: Long-term aspirin use was associated with reduced risk of total mortality, primary due to reduced risk of dying from cancers. Citation Format: Yin Cao, Meir Stampfer, Walter Willett, Donna Spiegelman, JoAnn Manson, Eric Rimm, Molin Wang, Shuji Ogino, Charles Fuchs, Edward Giovannucci, Andrew Chan. Long-term aspirin use and total and cancer-specific mortality [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3012. doi:10.1158/1538-7445.AM2017-3012

Aspirin Use Reduces the Risk of Aggressive Prostate Cancer and Disease Recurrence in African-American Men.

Background: Men of African descent experience a disproportionately high prostate cancer mortality. Intratumoral inflammation was found to be associated with aggressive prostate cancer. We and others have shown that prostate tumors in African-American (AA) patients harbor a distinct immune and inflammation signature when compared with European-American (EA) patients. These observations suggest that inflammation could be a driver of aggressive disease in men of African descent, leading to the hypothesis that an anti-inflammatory drug like aspirin could prevent disease progression.Methods: We examined the relationship between aspirin use and prostate cancer in the NCI-Maryland Prostate Cancer Case-Control Study consisting of 823 men with incident prostate cancer (422 AA and 401 EA) and 1,034 population-based men without the disease diagnosis (486 AA and 548 EA).Results: We observed a significant inverse association between regular aspirin use and prostate cancer among AA men. Stratification of AA patients by disease stage showed that daily and long-term (>3 years) aspirin use significantly decreased the risk of advanced disease [adjusted ORs for T3/T4 disease: 0.35, 95% confidence interval (CI), 0.17-0.73; and 0.22, 95% CI, 0.08-0.60, respectively], but not early-stage disease (T1/T2). Regular aspirin use also reduced disease recurrence in AA men.Conclusions: Regular aspirin use is associated with a decreased risk of advanced stage prostate cancer and increased disease-free survival in AA men.Impact: Regular aspirin use before and after a prostate cancer diagnosis may prevent the development of aggressive disease in AA men who are at risk of a lethal malignancy. Cancer Epidemiol Biomarkers Prev; 26(6); 845-53. ©2017 AACR.

Exploratory plasma proteomic analysis in a randomized crossover trial of aspirin among healthy men and women.

Long-term use of aspirin is associated with lower risk of colorectal cancer and other cancers; however, the mechanism of chemopreventive effect of aspirin is not fully understood. Animal studies suggest that COX-2, NFκB signaling and Wnt/β-catenin pathways may play a role, but no clinical trials have systematically evaluated the biological response to aspirin in healthy humans. Using a high-density antibody array, we assessed the difference in plasma protein levels after 60 days of regular dose aspirin (325 mg/day) compared to placebo in a randomized double-blinded crossover trial of 44 healthy non-smoking men and women, aged 21–45 years. The plasma proteome was analyzed on an antibody microarray with ~3,300 full-length antibodies, printed in triplicate. Moderated paired t-tests were performed on individual antibodies, and gene-set analyses were performed based on KEGG and GO pathways. Among the 3,000 antibodies analyzed, statistically significant differences in plasma protein levels were observed for nine antibodies after adjusting for false discoveries (FDR adjusted p-value<0.1). The most significant protein was succinate dehydrogenase subunit C (SDHC), a key enzyme complex of the mitochondrial tricarboxylic acid (TCA) cycle. The other statistically significant proteins (NR2F1, MSI1, MYH1, FOXO1, KHDRBS3, NFKBIE, LYZ and IKZF1) are involved in multiple pathways, including DNA base-pair repair, inflammation and oncogenic pathways. None of the 258 KEGG and 1,139 GO pathways was found to be statistically significant after FDR adjustment. This study suggests several chemopreventive mechanisms of aspirin in humans, which have previously been reported to play a role in anti- or pro-carcinogenesis in cell systems; however, larger, confirmatory studies are needed.

Long-Term Aspirin Use Reduces Cancer Mortality &amp; Risk of Developing Cancer

Long-Term Aspirin Use Reduces Cancer Mortality &amp; Risk of Developing Cancer

651 - Long-Term Use of Low-Dose Aspirin can Reduce Multiple Gastrointestinal Cancer Incidence and Mortality: A 10-Year Population-Based Study

651 - Long-Term Use of Low-Dose Aspirin can Reduce Multiple Gastrointestinal Cancer Incidence and Mortality: A 10-Year Population-Based Study

Long-term aspirin use and intratumoral gene expression in prostate cancer.

106 Background: Pharmacoepidemiologic studies suggest prognostic benefits of aspirin in prostate cancer. We hypothesized that prostate cancer tissue from regular aspirin users at cancer diagnosis compared to nonusers is characterized by specific transcriptional changes. Methods: We analyzed tumor whole-transcriptome data from men diagnosed with prostate cancer during prospective follow up of the Physicians Health Study 1 (PHS1, n1 = 150), initially a randomized-controlled trial of aspirin for prevention of cardiovascular disease and cancer. We compared the expression of putative aspirin target genes ( PTGS2, CTNNB1, MYC, AXIN2, PTGER3) between regular aspirin users ( ≥ 3 x 324 mg/week) and non-users at cancer diagnosis. We used Gene Set Enrichment Analysis to identify Gene Ontology biological process gene sets (total, 3609) associated with aspirin use. Leading edge genes of ≥ 3 functionally related gene sets were summarized in a meta-gene score. Results were validated among prostate cancer patients from the Health-Professionals Follow-up Study (HPFS, n2 = 254; aspirin use, ≥ 2 x/week). Results: Regular aspirin use was common (65% in PHS1; 45% in HPFS) and not associated with age, stage, and Gleason grade. In PHS1, none of the predefined genes were associated with aspirin use (all p &gt; 0.05). 26 gene sets were downregulated in aspirin users at a false discovery rate (FDR) &lt; 0.25 (9 at FDR &lt; 0.05). 11 gene sets were clustered functionally around ribosome function and protein translation. A “ribosome” score of 96 genes was higher in aspirin users compared to nonusers (difference, 35.5 standard deviations [SD]; p = 0.0001). There was no dose-dependency for cumulative duration of aspirin use before cancer diagnosis ( ptrend = 0.17) or time since stopping use among non-users at diagnosis ( p = 0.32). In HPFS, neither the pre-defined target genes (all p &gt; 0.18) nor the score were associated with aspirin use (difference, –9.8 SD; p = 0.18). Conclusions: Although RNA acetylation and resulting intratumoral gene expression changes due to aspirin use may be biologically plausible, we were unable to corroborate this association in two-long term prospective studies. Short-term trials might assess if aspirin has direct effects on tumor gene expression.

Comparing mortality of colorectal cancer and gastrointestinal bleeding among patients with long-term use of low dose aspirin: A population-based study of 689,209 patients.

527 Background: Aspirin, commonly used for prevention of cardiovascular and cerebrovascular diseases, is well-known to protect against colorectal cancer (CRC) development but increase risk of gastrointestinal bleeding (GIB). Few large-scale studies have compared the benefit and risk of long-term aspirin usage. This cohort study aims to evaluate the use of low-dose aspirin to prevent CRC and the risk of GIB associated with the aspirin use. Methods: A population-based clinical dataset was used to compare incidence and mortality of CRC and GIB patients receiving low-dose aspirin with sex-and-age matched controls (in 1:2 ratio). Patients with aspirin≤6 months were excluded. Clinical data of 206,243 aspirin users (mean dose 80 mg/day, mean duration 7.7 years) and 482,966 non-users were included. All patients must have at least 10-year follow up on clinical outcome. Results: Among aspirin users 5,776 (2.80%) were diagnosed with CRC; 2,097 (1.02%) died of the malignancy. 16,483 (3.41%) non-users were diagnosed with CRC; 7,963 (1.65%) died of CRC. Using the cox-proportional hazard regression, aspirin usage showed a modest but significant reduction in CRC mortality (HR = 0.65; 95% CI = 0.62 to 0.69). On the other hand, 11,187 (5.42%) aspirin users developed GIB, and 841 (0.41%) died. 15,186 (3.14%) non-users developed GIB, and 1,682 patients (0.35%) died. Aspirin users showed modest but significant increased risk of GIB-related mortality (HR = 1.24; 95% CI = 1.14 to 1.35). Conclusions: The long-term use of low dose aspirin shows preventive effect on CRC, but also increases the associated GIB risk. Considerations of prophylactic use of aspirin should balance the benefit and the risk of this treatment to the target population. [Table: see text]

Highlights of This Issue

The prevalence of metabolically unhealthy phenotype in normal-weight adults is 30%, but few studies have explored the association between metabolic phenotype and colorectal cancer incidence in normal-weight individuals. Liang and colleagues used data from the Women's Health Initiative to study this association. Women with one or none of the four components (elevated triglycerides, low HDL-C, elevated blood pressure, and elevated fasting glucose) were classified as metabolically healthy. Among normal-weight women, those who were metabolically unhealthy had higher risks of colorectal cancer compared with those who were metabolically healthy.Evidence suggests that long-term use of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) protects against colorectal cancer (CRC). Park and colleagues tested whether the inverse associations between NSAID use and CRC is similarly observed across sexes and five racial/ethnic groups. Use of aspirin and other NSAIDs was associated with a lower incidence of CRC in men but not in women. Further, the findings suggest that the benefit of NSAIDs for CRC may be strongest for white men and generalizes to African American, Japanese, and Latino but not to Native Hawaiian men.Percent breast density (PBD) is a strong risk factor for breast cancer that is influenced by several other factors. Alcohol consumption is associated with an increased risk of breast cancer with an uncertain association with PBD. Ziembicki and colleagues present a systematic review and meta-analysis to examine the association of alcohol consumption with PBD. Meta-analysis of 11 studies found a statistically significant difference in PBD when comparing the highest with the lowest alcohol consumption level, suggesting a positive association between alcohol intake and PBD.Farris and colleagues examined the associations between postdiagnosis physical activity and change from prediagnosis physical activity with quality of life (QoL) in prostate cancer survivors. In this study, prostate cancer survivors were followed over seven years with interviews/questionnaires to capture QoL outcomes. Both total and recreational physical activities were positively associated with physical QoL. Men who met physical activity guidelines had significantly higher physical and mental QoL scores compared with those who did not meet guidelines. Further, those who adopted and met guidelines had increased QoL, while those who relapsed experienced decreased QoL.

Exploring Differences in the Aspirin-Colorectal Cancer Association by Sex and Race/Ethnicity: The Multiethnic Cohort Study.

Evidence has accumulated that long-term use of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) protects against colorectal cancer. We tested whether the inverse associations between NSAIDs and colorectal cancer is similarly observed across sexes and five racial/ethnic groups (Japanese, Latino, African American, Native Hawaiian, and white) in the Multiethnic Cohort (MEC) Study. During a mean follow-up of 16.1 years, we identified 4,882 invasive incident colorectal cancer cases among 183,199 eligible participants. Cox proportional hazards models were used to calculate HRs and 95% confidence intervals (CI). Use of aspirin and other NSAIDs was associated with a lower incidence of colorectal cancer in men (HR = 0.77; 95% CI, 0.69-0.86 for current vs. never users of aspirin) but not in women (Pinteraction = 0.005). Among male current users, a reduced risk was observed with ≥6 years of aspirin or total NSAID use. The inverse association with current NSAID use in men was observed in all racial/ethnic groups, except for Native Hawaiians, and was stronger in whites. Our findings suggest that the benefit of NSAIDs for colorectal cancer may be strongest for white men and generalizes to African American, Japanese, and Latino, but not to Native Hawaiian men. The lack of inverse association observed in women and Native Hawaiian men in the MEC should be interpreted with caution. As only very few ethnic/racial groups are likely to be represented in trials of NSAIDs and colorectal cancer, it is important to conduct prospective observational studies in various populations to test the generalizability of their results. Cancer Epidemiol Biomarkers Prev; 26(2); 162-9. ©2016 AACR.

Abstract PR06: Interactions between nonsteroidal anti-inflammatory drugs and other risk factors on colorectal cancer risk

Abstract Background: Long-term use of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) has been shown to be protective against colorectal cancer (CRC). While aspirin is recommended to prevent cardiovascular disease and colorectal cancer in certain subgroups, a broad recommendation is not in place due to concerns about side effects. Evidence from clinical trials among patients with colorectal adenomas suggested stronger effect of aspirin among non-smokers, compared to current smokers; but the effect has not been evaluated for CRC risk. Methods: Using 11,894 cases and 15,999 controls from the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO) and the Colon Cancer Family Registry (CCFR), we performed multivariate logistic regression models to test for the interaction between regular use of NSAIDs (aspirin and non-aspirin NSAIDs) and other CRC risk factors on CRC risk, including age, sex, body mass index (BMI), physical activity, smoking, alcohol consumption, screening, family history of CRC, hormone replacement therapy (HRT) use, as well as intake of fruit, vegetables, red meat, processed meat, dietary fiber, total calcium and total folate. Fixed-effects meta-analyses with inverse variance weighting were used to summarize the estimates from interactions and stratified analyses across studies for each risk factor. A p-value &amp;lt;0.05 was considered statistically significant. Results: Regular use of any NSAID, aspirin, or non-aspirin NSAIDs was statistically significantly associated with a lower risk of CRC across almost all subgroups stratified by sex, body mass index (BMI), smoking, alcohol intake, physical activity and dietary factors. The association between aspirin and CRC risk statistically significantly differed by smoking status after adjusting for other risk factors (p-interaction=0.048). Regular aspirin use was associated with a 25% lower risk of CRC among non-smokers (OR=0.75; 95% CI: 0.64, 0.87), while it was associated with 19% and 16% lower risk of CRC among smokers of lower pack-years (OR=0.81; 95% CI: 0.70, 0.94) and higher pack-years (OR=0.84; 95% CI: 0.73, 0.97), respectively. There was a suggestive interaction between regular use of aspirin and BMI (p-interaction=0.081), where the effect of regular use of aspirin on CRC risk was stronger among individuals with normal BMI (OR=0.77; 95% CI: 0.65, 0.92) and overweight (OR=0.77; 95% CI: 0.66, 0.90), and non-significant among the obese (OR=0.93; 95% CI: 0.80, 1.08). Similarly, the association between any NSAID use and CRC risk was suggested to differ by BMI (p-interaction=0.075). No interaction between non-aspirin NSAIDs and other risk factors of CRC was observed. Conclusions: Our results suggest that the association between regular use of aspirin, but not other NSAIDs, and CRC risk may be modified by smoking status and BMI. The beneficial effect of aspirin on CRC risk appears to be diminished among those with greater CRC risk due to obesity and heavy smoking. The observed effect modifications were borderline significant and did not account for multiple comparisons. This abstract is also being presented as Poster A33. Citation Format: Xiaoliang Wang, Andrew T. Chan, Martha L. Slattery, Jenny Chang Claude, John D. Potter, Steven Gallinger, Caan Bette, Johanna W. Lampe, Polly A. Newcomb, Niha Zubair, Li Hsu, Robert E. Schoen, Hermann Brenner, Loic Le Marchand, Ulrike Peters, Emily White. Interactions between nonsteroidal anti-inflammatory drugs and other risk factors on colorectal cancer risk. [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer: From Initiation to Outcomes; 2016 Sep 17-20; Tampa, FL. Philadelphia (PA): AACR; Cancer Res 2017;77(3 Suppl):Abstract nr PR06.

Aspirin Use and Reduced Risk of Pancreatic Cancer.

Few options besides the avoidance of smoking and obesity are available to prevent pancreatic cancer. The association between aspirin use and risk of pancreatic cancer has been inconsistent across studies. We performed a population-based study of 761 case and 794 control subjects frequency matched on sex and age during 2006 to 2011 in Shanghai, China. Participants were asked about episodes of regular use of aspirin, tablets per day or week, and ages that the use started and stopped. Data were analyzed by unconditional logistic regression, with adjustments for age, sex, education, body mass index, years of cigarette smoking, cigarettes smoked per day, Helicobacter pylori CagA seropositivity, ABO blood group, and history of diabetes mellitus. Meta-regression was carried out to summarize the literature. Ever-regular use of aspirin was associated with lowered risk of pancreatic cancer: OR = 0.54; 95% confidence interval (CI), 0.40-0.73; P = 10-4.2 Risk decreased 8% per each cumulative year of use: ORtrend = 0.92; 95% CI, 0.87-0.97; P = 0.0034. Across this and 18 published studies of this association, the OR for ever-regular use decreased with increasingly more recent mid-study year, for any aspirin type (Ptrend = 10-5.1), and for low-dose aspirin (Ptrend = 0.0014). Regular use of aspirin thus appears to reduce risk of pancreatic cancer by almost half. People who take aspirin for prevention of other diseases likely also reduce their risk of pancreatic cancer. Aside from benefits for both cardiovascular disease and certain cancers, long-term aspirin use entails some risks of bleeding complications, which necessitates risk-benefit analysis for individual decisions about use. Cancer Epidemiol Biomarkers Prev; 26(1); 68-74. ©2016 AACR.