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Regular aspirin could lower colorectal cancer risk – US study

The regular use of aspirin and NSAIDs has been linked to a lower risk for early-onset adenomas, especially those with advanced histology, according to a researcher at Digestive Disease Week in Chicago, who said their recent study had revealed aspirin could be effective in preventing early-onset colorectal cancer cases, which are increasing.

“When you look at trends, specifically for 20- to 49-year-olds, these have been increasing for years, and all stages of the disease have also been increasing in incidence,” said Dr Cassandra Fritz, assistant professor of gastroenterology at Washington University School of Medicine.

“The proportion of early-onset colorectal cancer cases and all newly diagnosed colorectal cancer… has doubled since 1995 and most early-onset colorectal cancer cases are sporadic.”

Their study, she added, had shown a 15% reduction for all adenomas and 33% for those with advanced histology, “which to us is quite substantial”.

“We have not seen that much (33%) previously, so I would think it definitely needs more study,” Fritz said.

“This finding is important given the alarming rise in the incidence and mortality of early-onset colorectal cancer (age < 50 years), and our limited understanding of the underlying drivers to direct prevention efforts.”

The study confirms evidence from 30 years of research that suggests regular aspirin use reduces cancer risk.

In patients with Lynch syndrome, the CAPP2 study showed that aspirin has a protective effect against colorectal cancer at 20 years’ follow-up.

While emerging data have suggested aspirin use may reduce later-onset colorectal cancer, it was not known if regular aspirin and NSAID use were associated with diminished risk of early-onset conventional adenomas, and especially the high-risk adenomas conferring greater malignant potential known to be the major precursor of early-onset colorectal cancer, reports Medscape.

An unpublished analysis of molecular markers by the study’s senior author, Yin Cao, ScD, MPH, also of Washington University, found that at least 57% of early-onset colorectal cancers developed from the conventional adenoma-carcinoma pathway.

The objective of the new study was to assess the association between regular aspirin or NSAID use at least twice weekly, with the risk of developing early-onset adenoma.

The analysis is based on an evaluation of data from the Nurses’ Health Study II of 32 058 women who had at least one colonoscopy before 50 (1991-2015).

High-risk adenomas included those that were at least 1cm with tubulovillous/villous histology or high-grade dysplasia, or the presence of at least three adenomas.

There were 1 247 early-onset adenomas, among which 290 were considered high risk. The risk of adenomas among patients who took aspirin or NSAIDs regularly for cardiovascular protection or for inflammatory conditions was lower than in those who did not.

While the association was similar for high-risk vs low-risk adenomas, the benefit was more pronounced for adenomas of tubulovillous/villous histology or with high-grade dysplasia (odds ratio, 0.67; 95% confidence interval, 0.51-0.89), a 33% reduction, compared with tubular adenomas (OR, 0.90; 95% CI, 0.79-1.0; P for heterogeneity = .02).

With later-onset adenomas, risk reduction was confined primarily to large (OR, 0.76; 95% CI, 0.62-0.93) or multiple adenomas (OR, 0.57; 95% CI, 0.40-0.83), but not adenomas of advanced histology (OR, 0.92; 95% CI, 0.73-1.17).

“With colorectal cancer rates increasing, we still don’t have any preventative strategies beyond screening. With this 15% reduction with aspirin/NSAIDS in early-onset adenoma – and particularly for the quite substantial 33% benefit in advanced adenoma with advanced histology – we need to think about a precision-based chemoprevention strategy for early-onset precursors of colorectal cancer,” Cao said.

The US Preventive Services Task Force issued a new recommendation in 2021 stating that colorectal cancer screening for people with average risk should start five years sooner, at 45.

“As we know,” Yin told the journal MDedge, “many younger adults are not screened. That’s why we’re looking into potential early-onset colorectal cancer chemopreventative agents.”

Study details

Aspirin and non-steroidal anti-inflammatory drug use and risk of precursors of early-onset colorectal cancer

Cassandra Fritz, Oluseye Oduyale; Long Nguyen, Xiaoyu Zong, Edward Giovannucci, Andrew Chan; Yin Cao.

Presented at Digestive Diseases Week in Chicago on 8 May 2023

We conducted a prospective analysis using the Nurses’ Health Study II to assess the association between regular aspirin or NSAID use (2+ times/week) with risk of early-onset adenoma overall and by malignant potential (high-risk vs. low-risk) among 32058 women with at least one lower endoscopy before age 50 years (1991-2015). High-risk adenomas included adenomas with size ≥1, tubulovillous/villous histology or high-grade dysplasia, or ≥ 3 adenomas. As secondary analyses, we also assessed the associations for later-onset adenomas among women with lower endoscopy at age 50 and above (1995-2015). Multivariable logistic regressions for clustered data were used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CI).

We documented 1247 early-onset adenomas of which 290 were high-risk adenomas. After adjusting for putative risk factors, regular aspirin/NSAID use was associated with a lower risk of adenomas with an OR of 0.85 (95% CI 0.75-0.95) compared with non-regular users. The association was similar for high-risk vs. low-risk adenomas (P for heterogeneity=0.44), but more pronounced for adenomas of tubulovillous/villous histology or with high-grade dysplasia with an OR of 0.67 (95% CI 0.51-0.89) compared to tubular adenomas (OR=0.90; 95% 0.79-1.03; P for heterogeneity=0.02). These findings were similarly observed among women without a family history of CRC or symptom indications for endoscopy.

For later-onset adenomas, although we observed similar findings for overall and high-risk adenomas, the risk reduction was primarily confined to large (OR=0.76; 95% CI 0.62-0.93) or multiple adenomas (OR=0.57; 95% CI 0.40-0.83), but not adenomas of advanced histology (OR=0.92; 95% CI 0.73-1.17).


Regular aspirin/NSAID use was associated with a lower risk of early-onset conventional adenomas, especially for adenomas of advanced histology. Our findings highlight the urgent need to evaluate aspirin and/or NSAIDs as promising agents for the prevention of early-onset colorectal cancer given the favourable risk-benefit profile in younger individuals.


MDedge article – Unprecedented drop seen in early colorectal cancer cases due to aspirin use (Open access)


Medscape article – Aspirin Use Tied to Lower Risk for Early Colorectal Cancer (Open access)


See more from MedicalBrief archives:


More younger people being diagnosed with colorectal cancer


US studies show colorectal cancer link to ultra-processed foods


Pre-diagnosis aspirin use may lower colorectal cancer mortality — American Cancer Society


Aspirin reduces the risk of colorectal cancer by 40%







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