Cancer Mortality

We identified four meta-analyses of trials examining the effect of ASA on cancer-related mortality. All examined cancer deaths in general, only one examined cancer deaths by site (e.g., gastrointestinal [colorectal, esophageal, pancreatic and stomach], prostate, kidney/bladder, and other solid tumors). ^8,10,44,128 Two were conducted by the same first author and suggested that daily aspirin for 5 years or more might reduce risk of cancer-related mortality.^8,10

A 2012 meta-analysis of 34 trials comparing daily ASA to no ASA found ASA was associated with a reduced risk of cancer-related mortality (OR, 0.85 [95% CI, 0.76 to 0.96]).¹⁰ When combined with non-vascular mortality data from an additional 17 trials (i.e., trials that did not specify cancer deaths), the association was still significant (p=0.005). The most beneficial effect occurred after 5 years of followup (OR, 0.63 [95% CI, 0.49 to 0.82]). In the same meta-analysis, pooled individual patient data showed that ASA reduced the risk of incident cancers in six trials after at least 3 years of followup.

Another 2012 meta-analysis of 23 trials comparing daily low-dose aspirin to placebo or no treatment found that ASA after at least 2.5 years of followup may reduce risk of non-vascular (RR 0.88 [95% CI, 0.81 to 0.96]) and cancer-related mortality (in 11 trials; RR, 0.77 [95% CI, 0.63 to 0.95]).¹²⁸ Included studies demonstrated a significant treatment effect after approximately 4 years of followup. Another 2012 meta-analysis, however, did not find a statistically significant reduction in cancer-related mortality (OR, 0.93 [95% CI, 0.84 to 1.03]) as reported in eight primary prevention (of vascular and/or nonvascular outcomes) trials.⁴⁴

A 2011 meta-analysis of eight trials (all designed to compare the use of ASA vs. placebo in the primary or secondary prevention of vascular disease) found that ASA use was associated with a reduced risk of cancer-related mortality (OR, 0.79 [95% CI, 0.68 to 0.92]).⁸ Individual patient data was available in seven trials; a significant effect on cancer-related mortality was seen only after 5 or more years of followup (HR, 0.62 [95% CI, 0.47 to 0.82]). There was no effect, however, on non-gastrointestinal (e.g., lung, prostate), stomach or esophageal cancers. Three trials provided data beyond 20 years of followup and also found a statistically significant reduce risk of cancer-related mortality (HR, 0.78 [95% CI, 0.70 to 0.87]) including non-gastrointestinal, cancers. The greatest absolute risk reduction occurred in patients aged 65 years or older after 20 years.

Cancer Incidence

With regards to cancer incidence, only one trial (the Women's Health Study⁶⁰) was included in a handful of the meta-analyses summarized below; otherwise the majority of data comes from case-control and cohort studies. Many investigators recommend additional research (i.e., trials) before making definitive conclusions about the protective effects of ASA, the size and timing of the chemopreventive benefit, any dose-response relationships and trends in subgroups analyses.

A 2012 meta-analysis of ASA chemoprevention on 12 selected cancer sites included 139 observational studies.¹²⁹ It demonstrated that regular ASA use is associated with a statistically significant reduced risk of colorectal cancer, esophageal cancer (RR, 0.61 [95% CI, 0.50 to 0.76]), esophageal and gastric cardia adenocarcinoma (RR, 0.64 [95% CI, 0.52 to 0.78]), gastric cancer (RR, 0.67 [95% CI, 0.54 to 0.83]), lung cancer (RR, 0.91 [95% CI, 0.84 to 0.99]), breast cancer (RR, 0.90 [95% CI, 0.85 to 0.95]), and prostate cancer (RR, 0.90 [95% CI, 0.85 to 0.96]). No statistically significant reductions in risk were seen in other cancer sites (i.e., pancreatic, endometrial, ovarian, bladder, and kidney). Although the observational data indicate a beneficial role of ASA on some cancer sites, results are heterogeneous across studies and unclear relationships exist between risk and dose and duration.

Another review examined the effects of regular ASA use on long-term cancer incidence and metastasis and compared the evidence from observational studies versus trials.¹³⁰ The authors aimed to assess the reliability of estimates of the effect of ASA use on risk and outcome of all types of cancer in 150 case-control and 45 cohort studies. For other cancers, they found that case-control and cohort studies yielded associations that were also consistent with those from trials, with reductions in risk of biliary, esophageal, and gastric cancer. Lastly, this study showed a reduction in risk of breast cancer with regular use of ASA, which was not seen in the trials.

Three meta-analyses examined the association between ASA use and lung cancer risk.^131-133 A 2011 meta-analysis found that regular ASA use (i.e., seven or more tablets per week) can significantly reduce lung cancer risk (OR, 0.80 [95% CI, 0.67 to 0.95]), however, when all 19 studies were pooled there was no significant effect.¹³³ A 2012 meta-analysis of 15 observational studies found a statistically significant decreased lung cancer risk (OR, 0.86 [95% CI, 0.76 to 0.98]); subgroup analyses by study type, study quality, and sex showed mixed results (e.g., protective effect in men but not women).¹³¹ A 2011 meta-analysis of individual patient level data from eight observational studies in the International Lung Cancer Consortium also found a statistically significant protective effect of any ASA use against lung cancer in men (RR, 0.73 [95% CI, 0.57 to 0.92]) but not women (RR, 1.02 [95% CI, 0.87 to 1.19]).¹³²

Four meta-analyses examined the association between regular ASA use and breast cancer risk.^134-137 A 2012 meta-analysis of 32 observational studies and one RCT⁶⁰ found that ASA use was associated with a statistically significant reduction in breast cancer risk (OR, 0.86 [95% CI, 0.81 to 0.92]).¹³⁷ The RCT, however, did not find a statistically significant effect (OR, 0.98 [95% CI, 0.87 to 1.09]).⁶⁰ A 2008 meta-analysis also found a reduced risk for breast cancer in 37 observational studies and one RCT⁶⁰ (RR, 0.87 [95% CI, 0.82 to 0.92]).¹³⁴ Two other meta-analyses of observational studies also found statistically significant reduction in breast cancer risk with ASA use: RR, 0.75 (95% CI, 0.64 to 0.88) in ten studies¹³⁶ and RR, 0.91 (95% CI, 0.83 to 0.98) in 26 studies.¹³⁵

A 2010 meta-analysis of 24 observational studies found a statistically significant reduced risk of prostate cancer in older adults (OR, 0.83 [95% CI, 0.77 to 0.89]).¹³⁸ It also found a statistically significant effect on advanced cancer (OR, 0.81 [95% CI, 0.72 to 0.92]).

Three meta-analyses examining the association between ASA use and gastric cancer risk showed mixed results.^139-141 One 2010 meta-analysis of 13 observational studies and one RCT showed there was no statistically significant effect of ASA use on gastric cancer risk (OR, 0.80 [95% CI, 0.54 to 1.19]).¹⁴⁰ while another 2010 meta-analysis of 21 observational studies showed a statistically significant effect (adjusted risk ratio, 0.81 [95% CI, 0.73 to 0.89]).¹⁴¹ A cohort study that also included a meta-analysis of 17 studies also showed a statistically significant protective effect against gastric (OR, 0.74 [95% CI, 0.64 to 0.87]).¹³⁹

Three meta-analyses examined the association between ASA use and esophageal cancer.^142-144 A 2012 meta-analysis of six observational studies, ever use of ASA had significantly reduced the risk of esophageal adenocarcinoma (OR, 0.68 [95% CI, 0.56 to 0.83]).¹⁴⁴ A 2011 meta-analysis also found a reduced risk of esophageal adenocarcinoma in 14 observational studies with ASA use (OR, 0.73 [95% CI, 0.65 to 0.83]).¹⁴² Another 2011 meta-analysis pooled seven case-control studies of ASA use found a statistically significant effect on esophageal squamous cell carcinoma (OR, 0.60 [95% CI, 0.48 to 0.76]).¹⁴³