Elsevier

Clinical Lung Cancer

Volume 13, Issue 1, January 2012, Pages 44-51
Clinical Lung Cancer

Original study
Meta-Analysis on the Association Between Nonsteroidal Anti-Inflammatory Drug Use and Lung Cancer Risk

https://doi.org/10.1016/j.cllc.2011.06.009Get rights and content

Abstract

Background

Nonsteroidal 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.

Methods

Eligible 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.

Results

A 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.

Conclusions

Aspirin 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.

Introduction

Lung cancer is the most common cancer worldwide with approximately 1.5 million newly diagnosed cases and is responsible for the death of an estimated 1 million people annually.1 Because the 5-year survival rate is only approximately 13% and traditional chemotherapy has reached a platform, identification of effective methods for chemoprevention is of increasing importance.

Nonsteroidal anti-inflammatory drugs (NSAIDs), especially aspirin, have emerged as the most potential chemopreventive agents because of their inhibitive effect on the cyclooxygenase (COX) enzymes, which may play an important role in carcinogenesis.2 Evidence from observational studies indicates that aspirin and other NSAID use is associated with a reduced risk of colorectal carcinomas,3, 4 as well as breast cancer with a pooled relative risk (RR) of 0.91 (95% confidence interval [CI]: 0.83-0.98).5 Aspirin also plays a protective role in esophageal and gastric cancer.6, 7 An analysis of daily aspirin versus no aspirin using individual patient data from eight randomized trials (performed originally for primary or secondary prevention of vascular events) has shown that aspirin can reduce risk of deaths from cancer by approximately 20%.8 Such a reduction in the incidence of cancer would be an extremely important achievement.

In 2005, a meta-analysis by Khuder et al revealed an inverse association between NSAID use and the risk of lung cancer (RR = 0.79, 95% CI: 0.66-0.95).9 However, after that, 13 inconsistent observational studies have been published on the role of NSAID use and lung cancer risk.10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22 Moreover, the cohort study from Feskanich et al of 109,348 women showed that the use aspirin (15 or more tablets per week) can increase the incidence of lung cancer compared with non-use (RR = 1.58, 95% CI: 1.19-2.09. Because there was no raw data available, this study was excluded from our analysis).15 Therefore, whether NSAID use can reduce the risk of lung cancer is still unclear and clarifying the potentially chemopreventive effect of NSAIDs is of great significance.

The overall aim of this meta-analysis was to evaluate the association between NSAID use (especially aspirin) and lung cancer risk from all cohort, case-control studies, and clinical trials published up to January 2011. Subgroup analyses including dose-response relationship, gender, and histology type of lung cancer were also executed.

Section snippets

Identification and Eligibility of Relevant Studies

We attempted to include all the cohort studies, case-control studies, and clinical trials published to date on the association between NSAID/aspirin use and lung cancer risk. Eligible studies were identified by searching the electronic literature PubMed, Medline, Embase, and ScienceDirect databases for relevant reports (last search update January 2011, covering the terms nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin, and lung cancer. We also checked the references of the selected

Results

Cohort and case-control studies of NSAID use and lung cancer are described in Table 1. We identified 11 cohort studies,11, 13, 14, 15, 22, 26, 27, 28, 35, 37, 38 13 case-control studies (including 1 doctoral thesis),10, 16, 17, 18, 19, 20, 21, 30, 31, 32, 33, 34, 36 and 3 clinical trials12, 25, 29 of NSAID/aspirin use in relation to risk of lung cancer. Two cohort studies which adopted a standardized incidence ratio (SIR) to estimate RR were eliminated. SIR is the ratio of observed cases to

Discussion

Aspirin and other NSAIDs have almost consistently been associated with a reduced risk of colorectal cancer,3, 4 and although more limited, there is some evidence indicating that aspirin acts as a protective agent on breast, gastric, and esophageal cancer.5, 6, 7 In this meta-analysis, summary estimates do not support that any use of NA-NSAID or overall NSAID is associated with lung cancer risk. Regular use of aspirin (7 tablets per week) can significantly reduce the risk of lung cancer.

A

Conclusion

Despite the limitations listed above, some interesting conclusions emerged. In summary, regular aspirin use (7 tablets per week) may have a chemopreventive value against lung cancer. There is no association between NA-NSAID or overall NSAID use and lung cancer risk. The optimal dose as well as duration of aspirin as an effective chemopreventive agent in lung cancer remains unclear. More and in-depth researches focused on identifying appropriate individuals for this new indication of aspirin and

Disclosure

All authors have no conflicts of interest.

Acknowledgements

This work was supported by National Natural Science Funds (Grant Nos. 81071643 and 30772549).

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