Association of aspirin and other non-steroidal anti-inflammatory drug use with incidence of non-Hodgkin lymphoma

Non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin, seem to have chemopreventive properties against several types of cancer, particularly colon cancer. Persons with rheumatoid arthritis, an autoimmune disease for which NSAIDs are used commonly, have been reported to be at lower risk of colon cancer but at elevated risk of non-Hodgkin lymphoma (NHL), raising the possibility that NSAIDs may be a risk factor for NHL. We evaluated the association of use of NSAIDs, arthritis history, and risk of NHL in a prospective cohort of 27,290 postmenopausal women from the state of Iowa. The frequency of use of aspirin and of other NSAIDs excluding aspirin (e.g., ibuprofen), as well as a physician diagnosis of rheumatoid arthritis (RA) or osteoarthritis (OA), were self-reported on a questionnaire mailed in 1992. The incidence of NHL was ascertained through annual linkages to the Iowa SEER Cancer Registry. Relative risks (RR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards regression. Through 7 years of follow-up, 131 cases of NHL were identified. Compared to women who did not use either aspirin or other non-aspirin NSAIDs, women using aspirin exclusively (RR = 1.71; 95% CI = 0.94-3.13), non-aspirin NSAIDs exclusively (RR = 2.39; 95% CI = 1.18-4.83), or both types of drugs (RR = 1.97; 95% CI = 1.06-3.68) were at increased risk of NHL. A diagnosis of RA (RR = 1.75; 95% CI = 1.09-2.79), but not OA (RR = 1.06; 95% CI = 0.67-1.68), was associated with risk of NHL, but the positive association of use of aspirin and other NSAIDs with NHL was independent of RA history. Multivariate adjustment for other NHL risk factors only attenuated slightly these associations, whereas exclusion of cases occurring during the first 2 years of follow-up strengthened the associations. These data suggest that use of NSAIDs, either aspirin or other non-aspirin NSAIDs, are associated positively with risk of NHL, and that this association is independent of RA history.     

History of allergy and reduced incidence of colorectal cancer, Iowa Women's Health Study.

Previous epidemiologic studies have reported that a history of allergy is associated with reduced risk of colorectal cancer and other malignancies. We studied the association between allergy history and incident colorectal cancer (n=410) prospectively in 21,292 Iowa women followed for 8 years. Allergy was defined from four self-reported questions about physician-diagnosed asthma (a), hay fever (b), eczema or allergy of the skin (c), and other allergic conditions (d). A history of any allergy was inversely associated with incident colorectal cancer: after multivariate adjustment, the hazard ratio (HR) was 0.74 [95% confidence interval (95% CI), 0.59-0.94]. Compared with women with no allergy, women reporting only one of the four types of allergy and women reporting two or more types had HRs of 0.75 (95% CI, 0.56-1.01) and 0.58 (95% CI, 0.37-0.90), respectively (P trend=0.02). The inverse association persisted in analyses restricted to any type of nonasthmatic allergy (HR, 0.73; 95% CI, 0.56-0.95). HRs were similar for rectal and colon cancers as well as for colon subsites: proximal and distal (HRs for any allergy ranged from 0.63 to 0.78 across these end points). Allergy history, which may reflect enhanced immunosurveillance, is associated with a reduced risk of colorectal cancer.     

PTGS2 (COX-2) -765G > C promoter variant reduces risk of colorectal adenoma among nonusers of nonsteroidal anti-inflammatory drugs.

Prostaglandin H synthase 2 (PTGS2) or cyclooxygenase-2 (COX-2) has been shown to play a key role in the regulation of inflammation, and its inhibition is associated with a reduced risk of colon cancer. The PTGS2 (COX-2) -765G > C promoter variant is located in a putative SP1 binding site and reduces PTGS2 expression. In a Minnesota-based case-control study of cases with adenomatous (n = 494) or hyperplastic polyps (n = 186) versus polyp-free controls (n = 584), we investigated the role of the PTGS2 -765G > C promoter polymorphism. Multiple logistic regression analysis was used, adjusting for age, body mass index, caloric intake, alcohol, fiber, sex, hormone use, and smoking. For colorectal adenoma, odds ratios (OR) compared with PTGS2 -765GG as reference were GC 1.00 [95% confidence interval (95% CI), 0.74-1.35] and CC 0.53 (95% CI, 0.22-1.28). For hyperplastic polyps, the comparable adjusted odds ratios were GC 0.97 (95% CI, 0.65-1.46) and CC 0.24 (95% CI, 0.05-1.11). Risk associated with the -765G > C variant differed by aspirin or other nonsteroidal anti-inflammatory drug (NSAID) use. Among nonusers of aspirin or other NSAIDs, the CC genotype conferred a significant decrease in risk of adenoma (OR, 0.26; 95% CI, 0.07-0.89). Use of aspirin or other NSAIDs reduced risk of adenoma only among those with the -765GG (wild type) and possibly -765CG genotypes (OR, 0.66; 95% CI, 0.48-0.92 and OR, 0.64; 95% CI, 0.40-1.02, respectively). These data suggest that COX-2 expression or activity may be beneficially suppressed, and risk of colorectal polyps reduced, by aspirin or other NSAIDs in PTGS2 -765GG (wild type) individuals and by the -765 CC variant genotype in nonusers of NSAIDs.     

Association between nonsteroidal anti-inflammatory drug use and the incidence of lung cancer in the Iowa women's health study.

BACKGROUND: Previous studies have suggested that use of aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs) may be associated with reduced risk of lung cancer, but the data are inconsistent and are limited particularly with respect to the effects of aspirin, separate from other NSAIDs. METHODS: The Iowa Women's Health Study is a prospective cohort of 41,836 Iowa women ages 55 to 69 years old at baseline in 1986. NSAID use was assessed in 1992. Over 10 years of follow-up, 403 incident cases of lung cancer were identified. The association of incident lung cancer with current use of aspirin or non-aspirin NSAIDs was analyzed after adjustment for lung cancer risk factors. Hazard ratios (HR) were estimated using multivariate COX proportional hazards regression. RESULTS: There were 27,162 women in the analytic cohort. After controlling for age, education, alcohol intake, pack-years, smoking status, body mass index, and total fruit intake, the RR of women taking six or more aspirin weekly was 1.21 (95% confidence interval, 0.92-1.59). The HR was 1.23 for women taking six or more non-aspirin NSAIDs weekly (95% confidence interval, 0.92-1.65). There was no statistically significant trend by frequency of use for either aspirin (P(trend) = 0.22) or non-aspirin NSAIDs (P(trend) = 0.53). Analyses by histologic type and smoking status yielded similar null results. Information on dosage and duration of use were not available for this analysis. CONCLUSION: These findings do not suggest that aspirin or other NSAIDs reduce risk of lung cancer in this cohort of postmenopausal women.     

Non-steroidal anti-inflammatory drugs and small cell lung cancer risk in the VITAL study

Few studies have examined the association between non-steroidal anti-inflammatory drug (NSAID) use and risk of small cell lung cancer (SCLC); among them, findings are mixed. Recently, we found that use of NSAIDs was differentially associated with lung cancer risk by histology. Here, we examine, more comprehensively, the association between individual NSAIDs and SCLC risk. 75,546 residents of western Washington State, ages 50-76, completed a baseline questionnaire in 2000-2002 and reported on their use of individual NSAIDs over the past 10 years. NSAID use was categorized as non-users, low (<4 days/week or <4 years), and high (≥4 days/week and ≥4 years). 111 SCLC were identified through linkage to a population-based cancer registry. Multivariable-adjusted Cox proportional hazards models including strong adjustment for smoking were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI). Compared to non-use, high use of regular-strength aspirin was associated with an elevated risk of SCLC (HR 1.78, 95% CI: 1.05-3.02; P-trend=0.03). Findings for low-dose aspirin were elevated but did not reach statistical significance. Use of non-aspirin NSAIDs was not associated with SCLC risk. Our findings provide further indication of heterogeneity in the association between aspirin and lung cancer morphologies. Large, prospective studies with comprehensive assessments of NSAID use and smoking history and data on both men and women, are needed in order to better understand the association between use of aspirin and SCLC.     

Radiation risk of incident colorectal cancer by anatomical site among atomic bomb survivors: 1958–2009

Radiation effects on colorectal cancer rates, adjusted for smoking, alcohol intake and frequency of meat consumption and body mass index (BMI) by anatomical subsite (proximal colon, distal colon and rectum) were examined in a cohort of 105,444 atomic bomb survivors. Poisson regression methods were used to describe radiation-associated excess relative risks (ERR) and excess absolute rates (EAR) for the 1958–2009 period. There were 2,960 first primary colorectal cancers including 894 proximal, 871 distal and 1,046 rectal cancers. Smoking, alcohol intake and BMI were associated with subsite-specific cancer background rates. Significant linear dose–responses were found for total colon (sex-averaged ERR/Gy for 70 years old exposed at age 30 = 0.63, 95% confidence interval [CI]: 0.34; 0.98), proximal [ERR = 0.80, 95% CI: 0.32; 1.44] and distal colon cancers [ERR = 0.50, 95% CI: 0.04; 0.97], but not for rectal cancer [ERR = 0.023, 95% CI: −0.081; 0.13]. The ERRs for proximal and distal colon cancers were not significantly different (p = 0.41). The ERR decreased with attained age for total colon, but not for proximal colon cancer, and with calendar year for distal colon cancer. The ERRs and EARs did not vary by age at exposure, except for decreasing trend in EAR for proximal colon cancer. In conclusion, ionizing radiation is associated with increased risk of proximal and distal colon cancers. The ERR for proximal cancer persists over time, but that for distal colon cancer decreases. There continues to be no indication of radiation effects on rectal cancer incidence in this population.     

Non-steroidal anti-inflammatory drug use and ovarian cancer risk: findings from the NIH-AARP Diet and Health Study and systematic review

Background

Chronic inflammation has been proposed as a risk factor for ovarian cancer. Some data suggest that anti-inflammatory medications may be protective against ovarian cancer; however, results have been inconsistent.

Methods

We evaluated the risk of epithelial ovarian cancer with regular use of NSAIDs prospectively in the NIH-AARP Diet and Health Study, using Cox proportional hazard models. We also examined the risk of common subtypes of epithelial ovarian cancer (serous, mucinous, endometrioid, clear cell, and other epithelial) with regular use of NSAIDs. In addition, we performed meta-analyses summarizing the risk of ovarian cancer with “regular use” of NSAIDs in previously published studies.

Results

We did not observe a significant association between regular use of NSAIDs with ovarian cancer risk in the AARP cohort (aspirin: RR 1.06, 95?% CI 0.87–1.29; non-aspirin NSAIDs: RR 0.93, 95?% CI 0.74–1.15); however, summary estimates from prospective cohort studies demonstrated that use of non-aspirin NSAIDs may reduce the risk of ovarian cancer (RR 0.88, 95?% CI 0.77–1.01). Although not significant, we found that mucinous tumors were inversely associated with non-aspirin NSAID use (RR 0.69, 95?% CI 0.23–2.10) in the AARP cohort, which was supported by the meta-analysis (RR 0.69, CI 0.50–0.94.)

Conclusion

Although results from the NIH-AARP cohort study were not statistically significant, our meta-analysis suggests that non-aspirin NSAIDs may be protective against ovarian cancer. Additional analyses, focusing on dose, duration, and frequency of NSAID use and accounting for ovarian cancer heterogeneity are necessary to further elucidate the association between NSAID use and ovarian cancer risk.     

Aspirin and other nonsteroidal anti-inflammatory drugs and breast cancer incidence in a large U.S. cohort.

Use of nonsteroidal anti-inflammatory drugs (NSAIDs), particularly aspirin, has consistently been associated with reduced risk of breast cancer in case-control studies. However, results from prospective studies have been less consistent. We examined the association between NSAID use and breast cancer incidence, adjusting for multiple breast cancer risk factors among 77,413 women in the Cancer Prevention Study II Nutrition Cohort. During follow-up from 1992 to 2001, we observed 3,008 cases of incident breast cancer. Information on NSAID use was obtained from a questionnaire completed at enrollment in 1992 or 1993 and was updated using follow-up questionnaires in 1997 and 1999. NSAID use was modeled using time-dependent variables to update exposure status. Neither current total NSAID use (aspirin and other NSAIDs combined) nor current aspirin use were associated with breast cancer incidence even at relatively high levels of use [rate ratio (RR), 1.07; 95% confidence interval (95% CI), 0.96-1.21 for > or =60 NSAID pills per month compared with no reported use of NSAIDs; RR, 1.01; 95% CI, 0.84-1.20 for > or =60 aspirin per month compared with no reported use of aspirin]. Even long-duration regular use (> or =30 pills per month for > or =5 years) was not associated with breast cancer incidence (RR, 1.05; 95% CI, 0.88-1.26 for total NSAIDs; RR, 0.88; 95% CI, 0.69-1.12 for aspirin). Although we cannot exclude a small reduction in breast cancer risk associated with NSAID use, the results of this study provide evidence against a large reduction in risk.     

Aspirin,other NSAIDs,and ovarian cancer risk (United States)

Objective: We sought to evaluate the association between ovarian cancer risk and use of aspirin and nonsteroidal anti-inflammatories. Methods: We prospectively assessed use of aspirin, nonsteroidal anti-inflammatories (NSAIDs), and acetaminophen use in relation to ovarian cancer risk among 76,821 participants in the Nurses' Health Study who had no history of cancer other than non-melanoma skin cancer. Women reported known and suspected ovarian cancer risk factors in biennial mailed questionnaires from 1976 to 1996, along with new diagnoses of ovarian cancer. Aspirin use was assessed in 1980, 1982, 1984, and 1988–1994. We assessed NSAID use in 1980, and both NSAID and acetaminophen use in 1990, 1992, and 1994. During 16 years of follow-up and 1,222,412 person-years, 333 cases of invasive epithelial ovarian cancer were confirmed. We used pooled logistic regression to control for age, body mass index, oral contraceptive use, smoking history, parity, postmenopausal hormone use, tubal ligation, and other potential ovarian cancer risk factors. Results: Aspirin use was not associated with ovarian cancer risk overall (RR for users compared with nonusers, 1.00, 95% confidence interval (CI 0.80–1.25). We found no association between aspirin dose (in number of weekly tablets) and ovarian cancer risk (RR for those taking 15 or more tablets weekly compared with nonusers, 0.98, 95% CI 0.63–1.52). Similarly, duration of aspirin use was not associated with risk (RR for aspirin use of 20 or more years, 0.99, 95% CI 0.69–1.43). In separate models assessing the relation between NSAID use and ovarian cancer risk we found a 40% reduction in risk among NSAID users versus nonusers (RR 0.60, 95% CI 0.38–0.95). However, when we examined this relationship in terms of days of NSAID use per month, we did not observe a dose–response with increasing NSAID use. Conclusions: We observed no association between aspirin use, dose, or duration and epithelial ovarian cancer risk. Although we found a modest reduction in risk associated with NSAID use, there was no dose–effect.     

Pre-diagnostic NSAID use but not hormone therapy is associated with improved colorectal cancer survival in women

Background:

Non-steroidal anti-inflammatory drugs (NSAIDs) and hormone therapy (HT) independently decrease the risk of colorectal cancer. However, their role in altering survival after a colorectal cancer diagnosis is not well established.

Methods:

We examined the association between the use of these common medications before diagnosis and colorectal cancer survival among women in western Washington State diagnosed with incident colorectal cancer from 1997 to 2002. Cases were ascertained using the Surveillance, Epidemiology and End Results cancer registry; mortality follow-up was completed through linkages to the National Death Index. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).

Results:

We observed no overall association between colorectal cancer survival and pre-diagnostic NSAID use. However, when stratified by tumour sub-site, NSAID use was associated with a reduced risk of colorectal cancer mortality for women diagnosed with proximal (HR=0.55; 95% CI: 0.32–0.92), but not distal or rectal (HR=1.32; 95% CI: 0.83–2.10) tumours. The usage of HT was not associated with colorectal cancer survival overall or by tumour sub-site.

Conclusion:

Usage of NSAIDs before diagnosis may be associated with improved colorectal cancer survival among women diagnosed with proximal tumours. The usage of HT does not appear to have a function in altering colorectal cancer mortality.     

Association of aspirin and nonsteroidal anti-inflammatory drug use with breast cancer.

OBJECTIVE: Previous epidemiological studies have suggested that use of aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs) may be associated with reduced risk of breast cancer, but some studies have been limited in their ability to separate the effects of aspirin from other NSAIDs or to account for breast cancer risk factors. METHODS: We examined the incidence of breast cancer in association with self-reported aspirin, as well as other nonaspirin NSAID use in a large prospective cohort of postmenopausal women (n = 27,616). Over 6 years of follow-up, 938 incident breast cancers were identified. RESULTS: After adjustment for other breast cancer risk factors, any current use of aspirin or other NSAIDs compared with no use was associated with a reduction in risk of breast cancer [relative risk (RR) = 0.80, 95% confidence interval (CI) 0.67-0.95]. There was a trend of decreasing risk of incident breast cancer with increasing frequency of aspirin use (P(trend) = 0.0011). The multivariate-adjusted RR of breast cancer was 0.71 (95% CI 0.58-0.87) for women who reported using aspirin six or more times per week compared with women who reported no use. These results did not depend on whether women had early or late stage breast cancer. No association was found between nonaspirin NSAID use and incident breast cancer. The adjusted RR of using other NSAIDs six or more times per week compared with no use was 1.01 (95% CI 0.83-1.25). CONCLUSION: This prospective study corroborates other reports that use of aspirin might reduce risk of breast cancer.     

CYP2C9 and UGT1A6 genotypes modulate the protective effect of aspirin on colon adenoma risk

Regular use of nonsteroidal anti-inflammatory drugs (NSAIDs) has a protective effect on the incidence of colon neoplasia. However, polymorphisms in NSAID-metabolizing enzymes may alter this effect. NSAIDs, particularly aspirin, are glucuronidated by UGT1A6 and some classes of NSAIDs are also metabolized by cytochrome P450 (CYP) 2C9. Both of these enzymes have slow-metabolizing, variant forms. We tested the hypothesis that the slow alleles of these enzymes can modify the inverse association between NSAIDs and colon neoplasia in the Minnesota Cancer Prevention Research Unit (CPRU) adenomatous polyp case-control study. CYP2C9 and UGT1A6 genotypes were determined for 474 adenoma cases and 563 controls. NSAID use was inversely associated with adenoma risk [odds ratio (OR), 0.63; 95% confidence interval (CI), 0.44-0.90 for aspirin; and OR, 0.50; 95% CI, 0.31-0.82 for nonaspirin NSAID]. However, this association was absent in aspirin users who carried the CYP2C9 variant alleles (OR, 0.88; 95% CI, 0.51-1.53) or who were homozygous wild-type UGT1A6 (OR, 0.86; 95% CI, 0.50-1.50). Carriers of both of these alleles who use aspirin were also not at reduced risk of adenomatous polyps (OR, 1.59; 95% CI, 0.68-3.73). The variants of these enzymes did not influence the association between nonaspirin NSAIDs and adenoma risk. These data indicate that the effectiveness of chemopreventive drugs can be modulated by the genotype of metabolizing enzymes.     

Alcohol consumption is associated with an increased risk of distal colon and rectal cancer in Japanese men: the Miyagi Cohort Study

The association between alcohol consumption and the risk of cancer of the proximal or distal colon or rectum remains controversial. We examined this association in a large population-based cohort of Japanese men. In 1990, a self-administered questionnaire on alcohol drinking and other health habits was delivered to 25,279 Japanese men aged 40 to 64 years of age. After exclusion of subjects who gave incomplete responses on alcohol drinking or prevalent cancer cases at the baseline, a total of 21,199 men remained. Of these, 307 men were diagnosed as having colorectal cancer after 11 years of follow-up. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), with adjustments made for potential confounders. Compared with never drinkers, past and current drinkers had multivariate HRs of 1.1 (95% CI, 0.6-1.9) and 1.6 (95% CI, 1.1-2.2) for colorectal cancer, respectively. A dose-response relationship with current volume of alcohol drinkers was observed for cancer of the distal colon and rectum, but not for proximal colon. The multivariate HRs for distal colon and rectal cancer among current heavy drinkers (45.6 g or more ethanol per day) as compared with never drinkers were 4.2 (1.6-10.7; p for trend=0.0002) and 1.8 (1.1-3.2; p for trend=0.04), respectively. In contrast, no significant linear association was found for proximal colon cancer (p for trend=0.2). These data indicate that alcohol consumption in Japanese men is associated with a statistically significant increased risk of cancer of the distal colon and rectum, but not cancer of the proximal colon.     

A large cohort study of nonsteroidal anti-inflammatory drug use and melanoma incidence

Results of laboratory studies indicate that nonsteroidal anti-inflammatory drugs (NSAIDs) may have chemopreventive activity and therapeutic efficacy against melanoma. However, few published epidemiological studies have examined the association between NSAID use and melanoma risk. We examined whether NSAID use was associated with melanoma risk among 63 809 men and women in the Vitamins and Lifestyle (VITAL) cohort study. Participants self-reported NSAID use (low-dose aspirin, regular or extra-strength aspirin, and nonaspirin NSAIDs) during the previous 10 years and data related to their melanoma risk factors on a baseline questionnaire. After linkage of the VITAL database to the NCI Surveillance, Epidemiology, and End Results cancer registry, 349 patients with incident melanoma were identified through December 31, 2005. Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of melanoma by NSAID use as categorized by overall use, duration of use, and dose (expressed as average number of days of use during the past 10 years). All statistical tests were two-sided. After adjusting for melanoma risk factors and indications for NSAID use, no association between NSAID use and melanoma risk was found. When use of at least 4 d/wk was compared with nonuse, no melanoma risk reduction was detected for any NSAID dose (HR = 1.12, 95% CI = 0.84 to 1.48), for any NSAID excluding low-dose aspirin (HR = 1.03, 95% CI = 0.74 to 1.43), for regular- or extra-strength aspirin (HR = 1.10, 95% CI = 0.76 to 1.58), or for nonaspirin NSAIDs (HR = 1.22, 95% CI = 0.75 to 1.99). Moreover, NSAID use was not associated with tumor invasion (P(interaction) = .38), tumor thickness (P(trend) = .98), or risk of metastasis (HR = 1.09, 95% CI = 0.32 to 3.62). NSAIDs do not appear to be good candidates for the chemoprevention of melanoma.     

A comparative case-control study of colorectal cancer and adenoma

We conducted a comparative case-control study of colorectal cancer and adenoma involving 221 cases with colorectal cancer, 525 cases with colorectal adenoma and 578 neighborhood controls. Daily vegetables intake was associated with lower risks of distal colon adenoma (relative risks (RR) = 0.59, 95% confidence interval (CI): 0.39-0.89) and rectal cancer (RR = 0.46, 95% CI: 0.25-0.84). Daily beans intake was associated with lower risk of colon adenoma (RR = 0.58, 95% CI: 0.37-0.91 for the proximal colon and RR = 0.63, 95% CI: 0.45-0.88 for the distal colon) and daily intake of seaweeds was associated with lower risk of rectal cancer (RR = 0.42, 95% CI: 0.22-0.82). Daily intake of fish and shellfish also showed an inverse association with the risk of colon adenoma (RR = 0.67, 95% CI: 0.45-0.99 for the proximal colon and RR = 0.70, 0.52-0.94 for the distal colon). Generally, intakes of animal or vegetable fat-rich foods, especially meats, were associated with decreases in risks of both adenoma and cancer, though the association of cancer was not statistically significant. Other than dietary factors, daily alcohol drinking was associated with an increased risk of adenoma in the proximal colon (RR = 1.95, 95% CI: 1.15-3.29) and ex-drinkers showed higher risks for colon adenoma and colorectal cancer. Sports or occupational activities and coffee drinking were inversely associated and family history of colorectal cancer was positively associated with the risk of both colorectal adenoma and cancer.     

Meta-analysis on the association between nonsteroidal anti-inflammatory drug use and lung cancer risk

BackgroundNonsteroidal anti-inflammatory drugs (NSAIDs), especially aspirin, have emerged as the most potential chemopreventive agents. However, epidemiologic studies reported a controversial association between NSAID use and lung cancer risk. We conducted a meta-analysis to summarize the evidence for such relationship.MethodsEligible studies were identified by searching the electronic literature PubMed, Medline, Embase, and ScienceDirect databases for relevant reports and bibliographies. Studies were included if they designed as cohort study, case-control study, or clinical trial on the NSAID exposure and lung cancer with sufficient raw data to analyzes. Relative risk (RR) or odds ratio (OR) was used to evaluate the association between NSAIDs and lung cancer. Stratified analysis was also performed.ResultsA total of 19 studies including 20,266 lung cancer cases met the inclusion criteria. To the effect of aspirin on lung cancer, the combined RR for cohort studies was 0.96 (95%confidence interval [CI]: 0.78-1.19) and OR for case-control studies was 0.87 (95%CI: 0.69-1.09). When restricted in exposure of aspirin use to 7 tablets per week, the OR was 0.80 (95%CI: 0.67-0.95). The summary risk estimates showed no significant association between non-aspirin NSAID or overall NSAID use and lung cancer risk.ConclusionsAspirin use with a dose of 7 tablets per week can significantly reduce lung cancer risk, whereas non-aspirin NSAIDs showed no chemopreventive value. Greater attention should be paid to identifying appropriate individuals for this new indication of aspirin and the optimal dose and duration as a chemopreventive agent.     

Non-steroidal anti-inflammatory drug use and brain tumour risk: a case–control study within the Clinical Practice Research Datalink

Purpose

The aetiology of primary brain tumours is largely unknown; the role of non-steroidal anti-inflammatory drugs (NSAIDs) or aspirin use and glioma risk has been inconclusive, but few population-based studies with reliable prescribing data have been conducted, and the association with meningioma risk has yet to be assessed.

Methods

The UK Clinical Practice Research Datalink was used to assess the association between aspirin and non-aspirin NSAID use and primary brain tumour risk using a nested case–control study design. Conditional logistic regression analysis was performed on 5,052 brain tumour patients aged 16 years and over, diagnosed between 1987 and 2009 and 42,678 controls matched on year of birth, gender and general practice, adjusting for history of allergy and hormone replacement therapy use in the glioma and meningioma models, respectively.

Results

In conditional logistic regression analysis, excluding drug use in the year preceding the index date, there was no association with non-aspirin NSAID use (OR 0.96, 95 % CI 0.81–1.13) or glioma risk comparing the highest category of daily defined dose to non-users; however, non-aspirin NSAID use was positively associated with meningioma risk (OR 1.35, 95 % CI 1.06–1.71). No association was seen with high- or low-dose aspirin use irrespective of histology.

Conclusions

This large nested case–control study finds no association between aspirin or non-aspirin NSAID use and risk of glioma but a slight increased risk with non-aspirin NSAIDs and meningioma.     

Nonsteroidal anti-inflammatory drugs and risk of esophageal and gastric adenocarcinomas in Los Angeles County.

BACKGROUND: Nonsteroidal anti-inflammatory drug (NSAID) use has been associated with a reduced risk of colon cancer; further epidemiologic data appear consistent for stomach and esophageal adenocarcinomas. Yet, data on potential confounding effects by upper gastrointestinal tract (UGI) disorders on adenocarcinomas of the UGI are limited. METHODS: This study recruited newly diagnosed patients with esophageal adenocarcinoma (n = 220), gastric cardia adenocarcinoma (n = 277), or distal gastric adenocarcinoma (n = 441) as well as 1,356 control subjects in Los Angeles County. Unconditional multivariable logistic regression analyses were done to evaluate the association between regular NSAID use, at least two pills per week for 1 month, and these cancers. RESULTS: Duration of regular use of aspirin and non-aspirin NSAIDs was associated with reduced relative odds of distal gastric adenocarcinoma [>5 years use versus no regular use: odds ratio (OR), 0.61; 95% confidence interval, 0.40-0.92; P(trend) = 0.009] and esophageal adenocarcinoma (OR, 0.60; 95% confidence interval, 0.38-0.95; P(trend) = 0.04) in multivariable models that included history of UGI disorders and other potential confounding factors. Daily regular use was also associated with statistically significant reduced ORs of these two tumor types. No significant heterogeneity in risk estimates was noted after stratification by history of UGI disorders for any of the sites studied. However, irregular users of NSAIDs also had reduced risk of these cancers when compared with nonusers. CONCLUSIONS: Results from this study support an inverse association between regular NSAID use and risk of esophageal and distal gastric adenocarcinomas in individuals with and without a history of UGI disorders with long duration and daily use, providing the greatest risk reduction. Reduced risk in irregular users suggests that factors other than an effect on cyclooxygenase may also be important.