Non-aspirin Non-aspirin Non-steroidal Anti-inflammatory Drugs Research Articles

Aspirin and NSAID use in association with molecular subtypes of prostate cancer defined by TMPRSS2:ERG fusion status.

The TMPRSS2:ERG (T2E) gene fusion is the most common rearrangement in prostate cancer (PCa). It is unknown if these molecular subtypes have a different etiology. We evaluated aspirin and non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) in association with T2E fusion status. Subjects were from a population-based case-control study of PCa. T2E fusion status for prostatectomy cases (n=346) was determined by fluorescence in situ hybridization. Medication use was determined from questionnaires. Logistic regression, controlling for age, race, PCa family history and PSA screening, was used to evaluate the association of T2E fusion status according to medication use. T2E fusion was present in 171 (49%) cases, with younger cases more likely to be fusion positive (P<0.01). Current aspirin use was associated with a 37% risk reduction of T2E-positive tumors (adjusted odds ratio (OR) 0.63, 95% confidence interval 0.43-0.93). Aspirin use was not associated with T2E negative PCa (adjusted OR 0.99, 0.69-1.42). There were no associations between PCa fusion status and use of nonaspirin NSAIDs or acetaminophen. Aspirin was associated with a significant reduction in the relative risk of T2E fusion positive, but not T2E negative, PCa. As inflammation and androgen pathways are implicated in prostate carcinogenesis, additional studies of anti-inflammatory medications in relation to these PCa subtypes are warranted.

Use of nonsteroidal anti-inflammatory drugs and risk of endometrial cancer: a nationwide case-control study.

We examined the association between use of low-dose aspirin and non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) and endometrial cancer risk in a nationwide case-control study. Cases were all women in Denmark diagnosed with endometrial cancer during 2000-2009. Age-matched female controls were randomly selected by risk-set sampling. Information on NSAID use was collected from the Prescription Registry and classified according to duration and intensity. Conditional logistic regression was used to calculate odds ratios (ORs) and 95 % confidence intervals (CIs), adjusting for potential confounders. Analyses were stratified by endometrial cancer type, and potential effect modification by parity, obesity, and hormone replacement therapy (HRT) use was investigated. We identified 5,382 endometrial cancer cases and 72,127 controls. Endometrial cancer was not associated with use of low-dose aspirin (OR 0.97, 95 % CI 0.89-1.05) or non-aspirin NSAIDs (OR 0.96, 95 % CI 0.91-1.02) compared with nonuse. The ORs did not vary with increasing duration or intensity of NSAID use or with type of endometrial cancer. Interaction analyses showed reduced endometrial cancer risk associated with low-dose aspirin use among nulliparous women (OR 0.82, 95 % CI 0.70-0.95) and with non-aspirin NSAID use among women having used HRT (OR 0.90, 95 % CI 0.82-0.99). We found no association between use of NSAIDs and endometrial cancer risk overall, although there were some indications of risk reductions associated with low-dose aspirin use among nulliparous women and with non-aspirin NSAID use among women having used HRT.

Aspirin, nonaspirin nonsteroidal anti-inflammatory drugs, acetaminophen and ovarian cancer survival

Aspirin and nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to decrease tumor progression in pre-clinical models of ovarian cancer, however the influence of these drugs on survival in women following a diagnosis of ovarian cancer is unknown. We included 1305 Australian women diagnosed with incident invasive epithelial ovarian cancer, recruited into a population-based case–control study. Use of aspirin, nonaspirin NSAIDs and acetaminophen in the 5 years preceding ovarian cancer diagnosis was assessed from self-reports. Deaths were ascertained up to October 2011 via linkage with the Australian National Death Index. Cox proportional hazards regression models were used to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CI). During a mean follow-up time of 4.9 years (SD 2.8 years), there were 834 deaths, of which 779 (93% of deaths) were from ovarian cancer. We found uniformly inverse, but non-significant, HRs for ever use in the last five years of aspirin, nonaspirin NSAIDs and acetaminophen compared with no use (adjusted HRs 0.92 [95% CI 0.81–1.06], 0.91 [95% CI 0.80–1.05] and 0.91 [95% CI 0.69–1.20], respectively). There was no evidence of any dose response trends. The results remained unchanged when we limited the outcome to ovarian cancer mortality. Associations did not differ by histologic subtype, age at diagnosis or stage. Given current interest in the role of aspirin and nonaspirin NSAIDs in cancer survival these results are noteworthy given they are the first to investigate these associations in women with ovarian cancer. Our results provide no strong evidence that pre-diagnostic use of aspirin or nonaspirin NSAIDs are associated with improved survival in women with ovarian cancer.

Comparison of Small-Bowel Mucosal Injury between Low-Dose Aspirin and Non-Aspirin Non-Steroidal Anti-Inflammatory Drugs: A Capsule Endoscopy Study

Background/Aims: The differences in the severity of small-bowel toxicity induced by aspirin and non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs) remain unclear. This study aimed at clarifying these differences in small-bowel mucosal injury by using capsule endoscopy (CE). Methods: We retrospectively compared the records of 78 and 40 obscure gastrointestinal bleeding patients receiving low-dose aspirin (LDA) and non-aspirin NSAIDs, respectively. All patients were found to have small-bowel mucosal injuries on CE. The two groups were compared for the number of small-bowel mucosal injuries and CE scores on the basis of the findings of CE. Results: The mean numbers of reddened lesions in the LDA group and non-aspirin NSAID group were 2.49 ± 3.15 and 1.65 ± 3.04; the mean numbers of erosions/ulcers 1.56 ± 3.75 and 6.08 ± 10.4, and the mean CE scores 154 ± 294 and 520 ± 758, respectively. The mean number of reddened lesions was significantly higher and the mean number of erosions/ulcers and CE scores significantly lower in the LDA group than in the other non-aspirin NSAID group. Conclusion: Small-bowel mucosal injuries were significantly milder in the LDA group than in the non-aspirin NSAID group, though reddened lesions were more frequent in the LDA group.

Aspirin, Nonaspirin Nonsteroidal Anti-inflammatory Drug, and Acetaminophen Use and Risk of Invasive Epithelial Ovarian Cancer: A Pooled Analysis in the Ovarian Cancer Association Consortium

Regular aspirin use is associated with reduced risk of several malignancies. Epidemiologic studies analyzing aspirin, nonaspirin nonsteroidal anti-inflammatory drug (NSAID), and acetaminophen use and ovarian cancer risk have been inconclusive. We analyzed pooled data from 12 population-based case-control studies of ovarian cancer, including 7776 case patients and 11843 control subjects accrued between 1992 and 2007. Odds ratios (ORs) for associations of medication use with invasive epithelial ovarian cancer were estimated in individual studies using logistic regression and combined using random effects meta-analysis. Associations between frequency, dose, and duration of analgesic use and risk of ovarian cancer were also assessed. All statistical tests were two-sided. Aspirin use was associated with a reduced risk of ovarian cancer (OR = 0.91; 95% confidence interval [CI] = 0.84 to 0.99). Results were similar but not statistically significant for nonaspirin NSAIDs, and there was no association with acetaminophen. In seven studies with frequency data, the reduced risk was strongest among daily aspirin users (OR = 0.80; 95% CI = 0.67 to 0.96). In three studies with dose information, the reduced risk was strongest among users of low dose (<100 mg) aspirin (OR = 0.66; 95% CI = 0.53 to 0.83), whereas for nonaspirin NSAIDs, the reduced risk was strongest for high dose (≥500 mg) usage (OR = 0.76; 95% CI = 0.64 to 0.91). Aspirin use was associated with a reduced risk of ovarian cancer, especially among daily users of low-dose aspirin. These findings suggest that the same aspirin regimen proven to protect against cardiovascular events and several cancers could reduce the risk of ovarian cancer 20% to 34% depending on frequency and dose of use.

Analgesic use and patterns of estrogen metabolism in premenopausal women.

Analgesic use has been hypothesized to reduce the risk of some cancers, with inverse associations between analgesics and colon cancer, and suggestive inverse associations for breast cancer. Estrogen metabolites (EM) have genotoxic and estrogenic potential; genotoxicity may differ by hydroxylation pathway. Analgesic use may impact patterns of estrogen metabolism; effects of analgesics on disease risk could be mediated through these patterns. We conducted a cross-sectional study among 603 premenopausal women in the Nurses' Health Study II. Frequency of aspirin, non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs), and acetaminophen use was reported via questionnaire; average frequency in 1997 and 1999 was calculated. Women provided urine samples between 1996 and 1999, collected during the mid-luteal phase of the menstrual cycle. Urinary EM were quantified using high-performance liquid chromatography-tandem mass spectrometry. We observed no association between analgesic use and estradiol, estrone, or specific pathways of estrogen metabolism. Women reporting more frequent aspirin use had lower methylated 2-catechols (e.g., 2-hydroxyestrone-3-methyl ether, 2+ days/week vs. non-use: 0.95 vs. 1.21pmol/mg creatinine; p difference = 0.01, p trend = 0.07). Non-aspirin NSAID use was positively associated with 17-epiestriol (4+ days/week vs. non-use: 2.48 vs. 1.52pmol/mg creatinine; p difference = 0.01, p trend = 0.11). Acetaminophen use was positively associated with total EM (2+ days/week vs. non-use: 236 vs. 198pmol/mg creatinine; p difference = 0.02, p trend = 0.11), 2-hydroxyestrone-3-methyl ether (1.6 vs. 1.1pmol/mg creatinine; p difference < 0.01, p trend = 0.02), and 16α-hydroxyestrone (17 vs. 12pmol/mg creatinine; p difference = 0.01, p trend = 0.05). This study provides the first assessment of analgesic use and patterns of estrogen metabolism in women. While we observed some associations between analgesics and individual EM, no clear patterns emerged.

Re: Nonsteroidal Anti-inflammatory Drug Use, Chronic Liver Disease, and Hepatocellular Carcinoma

We read with interest the recent article by Sahasrabuddhe et al. (1) demonstrating a reduced risk of hepatocellular carcinoma (HCC) among aspirin users (relative risk [RR] = 0.59) and a reduced risk of death due to chronic liver disease among aspirin users (RR = 0.55) and nonaspirin nonsteroidal anti-inflammatory drug (NSAID) users (RR = 0.74). We have serious concerns about residual bias that should be considered in interpreting these results. Although the authors account for multiple confounders in their analysis, they do not include a measure of liver disease severity or cirrhosis. These factors are vital in examining the relationship between NSAID use and liver-related outcomes because they directly affect the decision to use NSAIDs in the first place. Gastroenterologists and hepatologists have long known that aspirin and nonaspirin NSAIDs induce renal vasoconstriction and reduce glomerular filtration in patients with cirrhosis (2,3). Such renovascular effects are particularly problematic in the setting of cirrhosis and portal hypertension, in which reduced renal perfusion can blunt the response to diuretics used for ascites management and trigger the hepatorenal syndrome. For this reason, clinical practice guidelines from the American Association for the Study of Liver Diseases advise against NSAID use in these patients (4). Furthermore, NSAIDs predispose patients with cirrhosis to variceal bleeding (5). Consequently, patients with cirrhosis are much less likely to be taking NSAIDs (6), presumably on the advice of their physicians. HCC in the United States develops in the setting of cirrhosis in the vast majority of cases (7), and liver related mortality is obviously linked to cirrhosis. Therefore, cirrhosis represents a major confounder that probably explains the observed inverse relationship between NSAIDs and the liver-related outcomes. In other words, the very patients most likely to die from liver failure or develop HCC are avoiding NSAIDs already, whereas those at much lower risk (noncirrhotics) are still able to take NSAIDs. The authors address confounding from cardiovascular disease and hypertension (1), but we believe that the presence of cirrhosis represents the much more pertinent bias. Our other concern is that the protective effects of aspirin on HCC and death due to chronic liver disease are independent from the frequency of use and that the relationship between nonaspirin NSAIDs and chronic liver disease death is only apparent for monthly users. Given the short half-life of aspirin and common nonaspirin NSAIDs, a benefit of monthly dosing lacks biologic plausibility. The authors rightly point out that the findings should be interpreted with caution because of this lack of dose response (1), but we would argue further that this finding is again reflective of unmeasured confounding due to cirrhosis. The potential relationship between NSAIDs, HCC, and chronic liver disease is an important issue that deserves further investigation. Our concerns about this study highlight the need to consider the diagnosis of cirrhosis in future epidemiologic studies.

Clinical features of gastroduodenal injury associated with long-term low-dose aspirin therapy

Low-dose aspirin (LDA) is clinically used for the prevention of cardiovascular and cerebrovascular events with the advent of an aging society. On the other hand, a very low dose of aspirin (10 mg daily) decreases the gastric mucosal prostaglandin levels and causes significant gastric mucosal damage. The incidence of LDA-induced gastrointestinal mucosal injury and bleeding has increased. It has been noticed that the incidence of LDA-induced gastrointestinal hemorrhage has increased more than that of non-aspirin non-steroidal anti-inflammatory drug (NSAID)-induced lesions. The pathogenesis related to inhibition of cyclooxygenase (COX)-1 includes reduced mucosal flow, reduced mucus and bicarbonate secretion, and impaired platelet aggregation. The pathogenesis related to inhibition of COX-2 involves reduced angiogenesis and increased leukocyte adherence. The pathogenic mechanisms related to direct epithelial damage are acid back diffusion and impaired platelet aggregation. The factors associated with an increased risk of upper gastrointestinal (GI) complications in subjects taking LDA are aspirin dose, history of ulcer or upper GI bleeding, age > 70 years, concomitant use of non-aspirin NSAIDs including COX-2-selective NSAIDs, and Helicobacter pylori (H. pylori) infection. Moreover, no significant differences have been found between ulcer and non-ulcer groups in the frequency and severity of symptoms such as nausea, acid regurgitation, heartburn, and bloating. It has been shown that the ratios of ulcers located in the body, fundus and cardia are significantly higher in bleeding patients than the ratio of gastroduodenal ulcers in patients taking LDA. Proton pump inhibitors reduce the risk of developing gastric and duodenal ulcers. In contrast to NSAID-induced gastrointestinal ulcers, a well-tolerated histamine H2-receptor antagonist is reportedly effective in prevention of LDA-induced gastrointestinal ulcers. The eradication of H. pylori is equivalent to treatment with omeprazole in preventing recurrent bleeding. Continuous aspirin therapy for patients with gastrointestinal bleeding may increase the risk of recurrent bleeding but potentially reduces the mortality rates, as stopping aspirin therapy is associated with higher mortality rates. It is very important to prevent LDA-induced gastroduodenal ulcer complications including bleeding, and every effort should be exercised to prevent the bleeding complications.

Aspirin and non-aspirin non-steroidal anti-inflammatory drug use and risk of lung cancer

There is evidence that aspirin and non-aspirin non-steroidal anti-inflammatory drug (NSAID) have anti-carcinogenic properties, but their effect on lung cancer, in particular in never-smokers, is unclear. Information on past or current use of anti-inflammatory medication was obtained in 398 Chinese female primary lung cancer cases and 814 controls in a hospital-based study in Singapore. 65% of cases and 88% of controls were never-smokers. Controls were excluded if they had been admitted for conditions associated with aspirin or NSAID use (n=174). Regular aspirin use (twice a week or more, for a month or more) was associated with a reduced risk of lung cancer (adjusted odds ratio [OR] 0.50, 95% confidence intervals [95%CI] 0.31–0.81 in non-smokers; OR 0.38, 95%CI 0.16–0.93 in smokers). Regular use of non-aspirin NSAID, paracetamol, steroid creams and steroid pills was uncommon and no association with lung cancer was detected. Our results suggest that aspirin consumption may reduce lung cancer risk in Asian women and are consistent with current understanding of the role of cyclooxygenase in lung carcinogenesis.

Use of nonaspirin nonsteroidal anti-inflammatory drugs during pregnancy and the risk of spontaneous abortion

The association between the use of nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs) during pregnancy and the risk of spontaneous abortion remains unclear because of inconsistent research results and the lack of evidence for an effect due to specific types or dosages of nonaspirin NSAIDs. We aimed to quantify the association between having a spontaneous abortion and types and dosages of nonaspirin NSAIDs in a cohort of pregnant women. Using a nested case-control design, we obtained data from the Quebec Pregnancy Registry for 4705 women who had a spontaneous abortion. For each instance, we randomly selected 10 controls from the remaining women in the registry who were matched by index date (date of the spontaneous abortion) and gestational age. Use of nonaspirin NSAIDs (identified by filled prescriptions) and nonuse were compared. We also looked for associations between different types and dosages of nonaspirin NSAIDs and having a spontaneous abortion. Analyses of associations and adjustment for confounding were done using conditional logistic regression. We identified 4705 cases of spontaneous abortion (352 exposed [7.5%]); 47 050 controls (1213 exposed [2.6%]). Adjusting for potential confounders, the use of nonaspirin NSAIDs during pregnancy was significantly associated with the risk of spontaneous abortion (odds ratio [OR] 2.43, 95% confidence interval [CI] 2.12-2.79). Specifically, use of diclofenac (OR 3.09, 95% CI 1.96-4.87), naproxen (OR 2.64, 95% CI 2.13-3.28), celecoxib (OR 2.21, 95% CI 1.42-3.45), ibuprofen (OR 2.19, 95% CI 1.61-2.96) and rofecoxib (OR 1.83, 95% CI 1.24-2.70) alone, and combinations thereof (OR 2.64, 95% CI 1.59-4.39), were all associated with increased risk of spontaneous abortion. No dose-response effect was seen. Gestational exposure to any type or dosage of nonaspirin NSAIDs may increase the risk of spontaneous abortion. These drugs should be used with caution during pregnancy.

Patient awareness of the adverse effects of aspirin and non-aspirin non-steroidal anti-inflammatory drugs

Abstract Objective To determine the extent to which patients reported having been informed about the adverse effects of aspirin and non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs) Method Questionnaire survey of 26 patients who had suffered an acute gastrointestinal bleed while taking aspirin, and 100 patients who had suffered an acute gastrointestinal bleed while taking a non-aspirin NSAID Setting Admissions to three United Kingdom hospitals. Patients were identified from endoscopy clinic records Key findings Five (19 per cent) of the aspirin-treated patients and 45 (45 per cent) of the non-aspirin NSAID-treated patients remembered having been informed of potential adverse effects, an odds ratio of 3.4 (95 per cent confidence interval 1.2–9.8, P&amp;lt;0.05). Five (19 per cent) of the aspirin-treated patients recalled having been advised what to do should adverse symptoms develop, whereas 44 (44 per cent) of the non-aspirin NSAID-treated patients did so, an odds ratio of 3.3 (95 per cent CI 1.2–9.5, P&amp;lt;0.05). Three (12 per cent) of aspirin-treated patients reported having been given an information leaflet, whereas 29 (29 per cent) of non-aspirin NSAID-treated patients did so, an odds ratio of 3.1 (95 per cent CI 0.9–11.2, P=0.08) Conclusion Our results suggest that aspirin-treated patients are less informed about their drug than are patients taking non-aspirin NSAIDs, in spite of the risk of gastrointestinal bleeding with which aspirin is associated

Analgesic use during pregnancy and risk of infant leukaemia: A Children's Oncology Group study

Background:Infant leukaemia is likely initiated in utero.Methods:We examined whether analgesic use during pregnancy was associated with risk by completing telephone interviews of the mothers of 441 infant leukaemia cases and 323 frequency-matched controls, using unconditional logistic regression.Results:With the exception of a reduced risk for infant acute myeloid leukaemias with non-aspirin non-steroidal anti-inflammatory drugs (NSAID) use early in pregnancy (odds ratios=0.60; confidence intervals: 0.37–0.97), no statistically significant associations were observed for aspirin, non-aspirin NSAIDs, or acetaminophen use in early pregnancy or after knowledge of pregnancy.Conclusion:Overall, analgesic use during pregnancy was not significantly associated with the risk of infant leukaemia.

Long-Term Use of Acetaminophen, Aspirin, and Other Non-Steroidal Anti-Inflammatory Drugs and Risk of Hematologic Malignancies: Results From the Large, Prospective VITamins and Lifestyle (VITAL) Cohort Study

AbstractAbstract 2153 Background:Several epidemiological studies have examined the association of aspirin use and other over-the-counter analgesics or anti-inflammatory drugs and the incidence of hematologic malignancies. Although previous results have been inconsistent, some studies have suggested a reduced risk of leukemia or lymphoma with regular use of aspirin or non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs). On the other hand, some but not all studies have reported an increased risk of leukemia or lymphoma with regular use of acetaminophen. Methods:We evaluated the association of analgesic use to hematologic malignancies in a prospective cohort of 64,839 men and women aged 50 to 76 years from Washington State recruited in 2000 to 2002 to the VITamins And Lifestyle (VITAL) study. Eligible participants completed a 24-page baseline questionnaire, including detailed questions about medication use during the previous 10 years. Incident cases of hematologic malignancies (n=577, including MDS [n=54], AML [n=36], myeloproliferative disorders [n=46], CLL/SLL [n=88] and other non-Hodgkin lymphomas [n=235], Hodgkin lymphomas [n=22], plasma cell disorders [n=66], mature NK/T cell neoplasms [n=17], and other entities [n=13]) were identified through December 2008 by linkage to the Seattle-Puget Sound Surveillance, Epidemiology, and End Results (SEER) cancer registry. The censored date was the date of withdrawal from the study, death, move out of the SEER catchment area, or last date of linkage to SEER for diagnosis of hematologic malignancy. In addition, participants were excluded if they had any cancer prior to baseline other than non-melanoma skin cancer and were censored at the time of diagnosis of a non-hematologic malignancy during follow-up to remove treatment for a prior cancer as a cause of any subsequent hematologic cancer. Medication use was categorized as “no use”, “low use” (use for either less than 4 days/week or less than 4 years), and “high use” (use for at least 4 days/week and at least 4 years). Hazards ratios (HRs) and 95% confidence intervals (95% CI) associated with use of acetaminophen, aspirin, and non-aspirin NSAIDs for total incident hematologic malignancies and cancer subcategories were estimated by Cox proportional hazards models. Multivariable-adjusted models were fit by adjusting for age, sex, race/ethnicity, education, smoking, self-rated health, history of fatigue/lack of energy, and family history of leukemia or lymphoma. All models except low-dose aspirin were further adjusted for history of rheumatoid arthritis, history or non-rheumatoid arthritis or chronic neck/back/joint pain, and history of migraines or frequent headaches. The model for low-dose aspirin was further adjusted for history of coronary artery disease, stroke, diabetes, or use of antihypertensive or lipid-lowering medications. Results:After adjustment, there was an increased risk of incident hematologic malignancies associated with increasing use of acetaminophen (HR=1.81 [95% CI: 1.33–2.46] for high use; p=0.009 for trend). The association with high use of acetaminophen was seen for MDS/AML (HR=2.23 [1.09-4.56]), non-Hodgkin lymphomas (HR=1.82 [1.14-2.92]), and plasma cell disorders (HR=2.32 [0.98-5.50]) but not CLL/SLL (HR=0.83 [0.30-2.35]). By comparison, there was no association with risk of incident hematologic malignancies for increasing use of low-dose aspirin (HR=1.04 [0.81-1.33] for high use; p=0.856 for trend), regular-dose aspirin (HR=0.86 [0.67-1.11] for high use; p=0.329 for trend), non-aspirin NSAIDs (HR=1.04 [0.75-1.43] for high use; p=0.820 for trend), or ibuprofen (HR=0.98 [0.67-1.44] for high use; p=0.956 for trend). Conclusion:Use of acetaminophen increased the risk of incident hematologic malignancies other than CLL/SLL in a usage-dependent manner, with an almost 100% increased risk for use least 4 days/week for of at least 4 years. Neither aspirin nor non-aspirin NSAIDs decreased risk and are unlikely to be useful for chemoprevention. Disclosures:No relevant conflicts of interest to declare.

Analgesic Use and Sex Steroid Hormone Concentrations in Postmenopausal Women

Prior epidemiologic studies suggest that regular use of analgesics may decrease risk of breast and ovarian cancer. We explored possible hormone-mediated mechanisms for these associations by examining the relationship between use of aspirin, nonaspirin nonsteroidal anti-inflammatory drugs (NSAID), and acetaminophen and sex steroid hormone concentrations among 740 postmenopausal women in the Nurses' Health Study. All women reported their analgesic use in 1988 or 1990 and provided a blood sample in 1989 to 1990. We calculated adjusted geometric mean estrogen and androgen levels for each category of analgesic use and calculated the P value for trend with increasing frequency of use. There was no association between days of use per month of aspirin, nonaspirin NSAIDs, or acetaminophen in 1990 and hormone levels (all P(trend) > or = 0.09). However, we observed significant inverse trends between the estimated number of aspirin tablets per month in 1988 and concentrations of estrone (P(trend) = 0.04) and estrone sulfate (P(trend) = 0.03). In analyses of total (aspirin and nonaspirin) NSAID use in 1990, women who used NSAIDs at least 15 days per month had significantly lower levels of estradiol compared with women with no NSAID use (P(trend) = 0.03). Frequency of use of all analgesics (aspirin, nonaspirin NSAIDs, and acetaminophen) in 1990 was inversely associated with concentrations of estradiol (P(trend) = 0.001), free estradiol (P(trend) = 0.01), estrone sulfate (P(trend) = 0.03), and the ratio of estradiol to testosterone (P(trend) = 0.04). Among postmenopausal women, regular users of aspirin and other analgesics may have lower estrogen levels than nonusers, which could contribute to a decreased risk of breast or ovarian cancer among analgesic users.

Anti-inflammatory drugs and risk of Parkinson disease

Anti-inflammatory drugs may prevent Parkinson disease (PD) by inhibiting a putative underlying neuroinflammatory process. We tested the hypothesis that anti-inflammatory drugs reduce PD incidence and that there are differential effects by type of anti-inflammatory, duration of use, or intensity of use. MEDLINE and EMBASE were searched for studies that reported risk of PD associated with anti-inflammatory medications. Random-effects meta-analyses were used to pool results across studies for each type of anti-inflammatory drug. Stratified meta-analyses were used to assess duration- and intensity-response. Seven studies were identified that met the inclusion criteria, all of which reported associations between nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs) and PD, 6 of which reported on aspirin, and 2 of which reported on acetaminophen. Overall, a 15% reduction in PD incidence was observed among users of nonaspirin NSAIDS (relative risk [RR] 0.85, 95% confidence interval [CI] 0.77-0.94), with a similar effect observed for ibuprofen use. The protective effect of nonaspirin NSAIDs was more pronounced among regular users (RR 0.71, 95% CI 0.58-0.89) and long-term users (RR 0.79, 95% CI 0.59-1.07). No protective effect was observed for aspirin (RR 1.08, 95% CI 0.92-1.27) or acetaminophen (RR 1.06, 95% CI 0.87-1.30). Sensitivity analyses found results to be robust. There may be a protective effect of nonaspirin nonsteroidal anti-inflammatory drug use on risk of Parkinson disease (PD) consistent with a possible neuroinflammatory pathway in PD pathogenesis.

Clinical Features of Gastroduodenal Ulcer in Japanese Patients Taking Low-Dose Aspirin

The risks of peptic ulcer complications increase in association with low-dose aspirin (LDA) use. The endoscopic findings and clinical features of gastroduodenal ulcer have not been thoroughly investigated in patients taking LDA. We classified 1,041 gastroduodenal ulcer patients into three groups [patients taking LDA (group A), patients taking nonaspirin nonsteroidal anti-inflammatory drug (NSAID) (group N), and patients taking neither aspirin nor nonaspirin NSAID (group C)] and 241 bleeding gastroduodenal ulcer patients into three corresponding groups (groups a, n, and c). We investigated the clinical features, endoscopic characteristics, and endoscopic treatment of the hemorrhagic lesion in the gastroduodenal ulcer patients taking LDA and compared them with those of the other groups. The frequency of bleeding events such as hematemesis, melena, and anemia was significantly higher in group A and N than in group C. The percentage of ulcers located in the antrum was higher in group A and N than in group C, and also higher in group a and n than in group c. The percentage of ulcers located in the body, fundus, and cardia was significantly higher in the bleeding patients than in all gastroduodenal ulcer patients. The percentage of cases that required additional endoscopic treatment in group a was higher than in group c. Duration of hospitalization of group a was significantly longer than that of group c. These results indicate that it is very important to prevent LDA-induced gastroduodenal ulcer complications, including bleeding.

Aspirin and other non-steroidal anti-inflammatory drugs and risk of colorectal cancer: A Danish cohort study

The optimal duration and dose of aspirin and non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs) in the potential prevention of colorectal cancer (CRC) have not been established. We examined this issue in the Danish Diet, Cancer, and Health Study. Self-reported NSAID use at entry (January 1995-May 1997) was updated through June 2006, using a nationwide prescription database. CRC incidence was ascertained from nationwide registers. Cox proportional hazards regression was used to compute confounder-adjusted incidence rate ratios (RRs) and 95% confidence intervals (CIs). From 51,053 cohort subjects, we identified 615 CRC cases during 1995-2006. Daily aspirin use at entry was associated with a decreased risk of CRC (RR, 0.73; 95% CI, 0.49-1.10). A similar risk reduction was seen among subjects with 10 or more prescriptions for aspirin or non-aspirin NSAIDs and five or more years of follow-up. Most aspirin prescriptions were for 75-150 mg aspirin tablets. Among non-aspirin NSAID users, only those with body mass index (BMI) above 25 showed risk reductions [RR, 0.69 (0.47-1.03) for 10 or more prescriptions]. Long-term consistent use of aspirin or non-aspirin NSAIDs appears necessary to achieve a protective effect against CRC. Further studies of the effective dose of aspirin and the potential interaction between NSAID use and BMI are warranted.

Abstract A116: Nonsteroidal anti-inflammatory drug use and risk of gastric and esophageal adenocarcinoma in a large cohort study

Abstract A116 Background Previous studies suggest that the use of aspirin or non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the risk of gastric and esophageal adenocarcinomas, but few studies have been prospective, have used data collected directly from subjects, and have controlled for the many potential confounders. Methods: We examined the association between aspirin or non-aspirin NSAID use and incident gastric noncardia (N=182), gastric cardia (N=178), and esophageal adenocarcinomas (N=228) in the NIH-AARP Diet and Health prospective cohort study with subjects followed for up to 7 years. We estimated the hazard ratios (HR) and 95% confidence intervals (CI) in Cox models for any use of aspirin or non-aspirin NSAIDs in the previous twelve months or for the typical frequency of use (at least monthly, weekly, or daily) with adjustment for age, sex, smoking, alcohol, BMI, education, physical activity, and fruit and vegetable intake. Results For gastric noncardia cancer, we found that any aspirin use had an HR (95%CI) of 0.64 (0.47-0.86) and for daily use 0.57 (0.39-0.85). The age-standardized incidence rates (95% CI) per 100,000 person years dropped from 11.0 (8.4-13.6) in non-aspirin users to 7.0 (5.7-8.3) in users. For any non-aspirin NSAID use we found an HR (95%CI) of 0.68 (0.51-0.92) and for daily use 0.82 (0.50-1.34). We found no significant association between NSAID use and gastric cardia cancer or esophageal adenocarcinoma. For the latter, any or daily aspirin use had HR (95% CI) of 1.00 (0.73-1.37) and 1.11 (0.78-1.57), respectively. Conclusions We found a strong association between NSAID use, especially aspirin, and reduced risk of noncardia gastric adenocarcinoma, but not adenocarcinoma of the gastric cardia or esophagus. Citation Information: Cancer Prev Res 2008;1(7 Suppl):A116.

Association of Aspirin and Nonaspirin Nonsteroidal Anti-inflammatory Drugs With Cancer Incidence and Mortality

The cancer chemopreventive benefits of aspirin and nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs) are incompletely defined and may vary by smoking history. We evaluated associations between aspirin and nonaspirin NSAID use with cancer incidence and mortality stratified by smoking history in the Iowa Women's Health Study, a prospective cohort of postmenopausal women. Aspirin and nonaspirin NSAID use was self-reported by questionnaire in 1992. Cancer incidence and mortality were ascertained by annual linkage to the Iowa Surveillance, Epidemiology, and End Results Cancer Registry and death certificates. Cox proportional hazards models were used to estimate multivariable relative risks (RRs) and 95% confidence intervals (CIs). All statistical tests were two-sided. During an average of 10 years of follow-up, 3487 incident cancer cases and 3581 deaths were observed in the cohort of 22,507 women. Compared with nonuse, aspirin use was inversely associated with total cancer incidence (multivariable-adjusted RR = 0.84, 95% CI = 0.77 to 0.90), with age-adjusted incidence rates of 147 and 170 per 10,000 person-years for ever and never users, respectively, and was inversely associated with cancer mortality (multivariable-adjusted RR = 0.87, 95% CI = 0.76 to 0.99), with age-adjusted rates of 47 and 52 per 10,000 person-years. The inverse relationship was stronger among former and never smokers than current smokers, although not statistically significantly (P = .28). Aspirin use was also inversely associated with coronary heart disease mortality (multivariable-adjusted RR = 0.75, 95% CI = 0.64 to 0.89), with age-adjusted rates of 23 and 30 per 10,000 person-years for ever and never users, respectively, and with all-cause mortality (multivariable-adjusted RR = 0.82, 95% CI = 0.76 to 0.89), with age-adjusted rates of 126 and 155 per 10,000 person-years. Nonaspirin NSAID use was not associated with cancer incidence or mortality, coronary heart disease mortality, or all-cause mortality. Aspirin use, but not nonaspirin NSAID use, was associated with lower risks of cancer incidence and mortality, which was more pronounced among former and never smokers than current smokers.

Nonsteroidal anti‐inflammatory drugs and risk of lung cancer

Regular aspirin and non-aspirin nonsteroidal anti-inflammatory drug (NSAID) use is associated with a reduced risk of colorectal cancer. The effect of NSAIDs on the risk of other cancers remains unclear. To evaluate whether use of aspirin or other specific NSAIDs protects against lung cancer, we conducted a case-control study nested in a cohort of subjects 40-84 years old in 1995-2004, without a diagnosis of cancer before the study start date, and with at least 2 years of enrollment with a general practitioner providing data to the The Health Improvement Network (THIN) database in the UK. Patients who had a first diagnosis of primary lung cancer during the study period were considered cases. A random sample of 10,000 controls was frequency-matched to the cases for age, sex and calendar year. The index date for exposure definition was 1 year before the date of diagnosis for cases and 1 year before a random date within the study period for controls. Relative risks and 95% confidence intervals were estimated using conditional logistic regression stratified for matching factors. Factors such as smoking, chronic obstructive pulmonary disease, cardiovascular diseases and body mass index were introduced in the model. We identified 4,336 cases with primary incident lung cancer (incidence rate 7.6 per 10,000 person-years). Compared with subjects with no prescription of non-aspirin NSAID prior to the index date, the risk of lung cancer was 0.76 (0.61-0.94) among those who received a prescription the previous year and had a treatment duration of at least 1 year. The corresponding relative risk was 1.15 (0.99-1.34) for aspirin. In conclusion, prescription of non-aspirin NSAIDs for at least 1 year might be associated with a slightly reduced risk of lung cancer. Aspirin was not associated with a risk reduction, perhaps due to residual confounding.