Aspirin Reduces Risk of Several Gastrointestinal Cancers

Corroborating earlier studies, regular aspirin use was associated with a reduced risk of gastrointestinal (GI) cancers, with a dose effect seen with colorectal cancer (CRC), a meta-analysis found.
The systematic review of cohort and case-control studies observed decreases in the risk of GI malignancies ranging from 22% for pancreatic cancer to 39% for gastric cardia and esophageal adenocarcinomas, Cristina Bosetti, MD, of the Istituto di Ricerche Farmacologiche Mario Negri IRCCS in Milan, Italy, and colleagues reported in Annals of Oncology.

Across over 100 studies examined, taking one or two aspirin per week was associated with the following risk reductions:

• Pancreatic cancer (relative risk [RR] 0.78, 95% CI 0.68-0.89)
• CRC (RR 0.73, 95% CI 0.69-0.78)
• Squamous-cell esophageal cancer (RR 0.67, 95% CI 0.57-0.79)
• Stomach cancer (RR 0.64, 95% CI 0.51-0.82)
• Hepatobiliary cancers (RR 0.62, 95% CI 0.44-0.86)
• Gastric cardia and esophageal adenocarcinoma (RR 0.61, 95% CI 0.49-0.77)

Risk of CRC, based on over 156,000 cases from nearly 50 studies, was further reduced with increased aspirin dosages.
“An aspirin dose between 75 and 100 mg a day was associated with a 10% reduction in a person’s risk of developing cancer compared to people not taking aspirin; a dose of 325 mg a day was associated with a 35% reduction, and a dose of 500 mg a day was associated with a 50% reduction in risk,” Bosetti said in a press statement. “However, the estimate for high-dose aspirin was based on just a few studies and should be interpreted cautiously.”

The findings align with those of previous meta-analyses, the authors wrote.
Emmanouil Pappou, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York City, said the findings support observational analyses showing a modest risk reduction in CRC with aspirin.
“The thing is you have to take aspirin for a long time, at least 10 years, to have a benefit, and a high dose is better. And most interventional studies have found no protective effect,” he said.
Pappou, who was not involved in the study, cautioned that the modest benefit should be weighed against the risk of bleeding, ulcers, and perforation, but said he does counsel his CRC patients that aspirin consumption may reduce their risk of recurrence and metastases.
“But it’s not an overall panacea,” he added. “Other health interventions can also reduce risk, such as regular moderate exercise, a healthy diet with less red meat, calorie reduction, maybe with some fasting, and colonoscopy, which can be used as screening and as an intervention.”

As to the chemopreventive potential of non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs), Pappou said the selective COX-2 inhibitor celecoxib (Celebrex) has been tied to a lower risk of colonic adenomas in high-risk persons, but has also been linked to more cardiovascular events.
While aspirin has long been observed to reduce CRC risk, the quantification of risk reduction and the optimal dose and duration of aspirin use for the prevention of CRC and other GI cancers has been unclear, the authors noted. To ascertain this, they reviewed all observational studies on aspirin and GI cancers published through March 2019.
The number of eligible studies ranged from five on hepatobiliary cancer to 45 on colorectal cancer. Risk estimates were consistent across sex, geographical areas, and other covariates. The association between head and neck cancer and aspirin use was also studied, but no risk reduction was observed.
The Italian researchers noted that aspirin’s chemopreventive effect has been linked to inhibition of cyclooxygenase (COX), the enzyme that synthesizes prostaglandins. It is abnormally expressed in many cancer cell lines and is implicated in carcinogenesis, tumor growth, and angiogenesis. Additional mechanisms may include apoptosis induction through non-COX pathways and the upregulation of tumor suppressor genes.

Limitations of the meta-analysis, the authors said, included inter-study heterogeneity and the inherent biases of observational studies. The inverse associations were generally stronger in case-control than cohort studies, which have a potential recall bias stemming from possibly stricter reporting of aspirin use in cases than controls.
In addition, confounding by indication due to selective aspirin avoidance in patients with early GI cancer symptoms may partly explain the stronger inverse associations in case-control studies. And the lower inverse associations reported in nested case-control studies, often based on prescription databases, may be due to misclassification of aspirin exposure because of lacking information on actual aspirin use, including over-the-counter products. Finally, most studies had no data on other medications, such as statins for cardiovascular protection, and that may have confounded the association between aspirin and cancer risk.

Disclosures

This study was supported by Bayer and the Italian Association for Cancer Research.
The authors report having no conflicts of interest.
Pappou disclosed no conflicts of interest.

Primary Source

Annals of Oncology

Source Reference: Bosetti C, et al “Aspirin and the risk of colorectal and other digestive tract cancers: An updated meta-analysis through 2019” Ann Oncol 2020; DOI: 10.1016/j.annonc.2020.02.012.

https://www.medpagetoday.com/gastroenterology/coloncancer/85984