A Little Aspirin Protects the Colon
Low-Dose Aspirin Cuts Colorectal Cancer Risk, Researchers Say
By NANCY WALSH, MedPage Today Contributing Writer
Sept. 18, 2010
Regular use of low-dose aspirin can cut the risk of colorectal cancer by a third, with benefits becoming apparent quickly, a large Scottish case-control study found.
After a just year, patients who took 75 mg/day of aspirin -- a lower dose than a standard baby aspirin -- reduced their risk of colon cancer by 13 percent compared with controls, according to Farhat V.N. Din of the University of Edinburgh and colleagues.
And after five years the relative risk reduction was 37 percent, the researchers reported online in Gut.
Epidemiologic studies have shown that aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) lower the incidence of colorectal cancer by about 40 percent, a finding supported by some, though not all, randomized trials.
"The key finding of our case-control study is that the daily 75 mg dose of aspirin is associated with a lower incidence of [colorectal cancer] in the general population," Din and colleagues wrote.
Some previous studies have suggested that higher doses might be needed for prevention of colorectal cancer, but "our data provide reassurance that lower doses of aspirin do provide worthwhile risk reduction effects," they observed.
Aspirin has not as yet been recommended for primary chemoprevention of colorectal cancer, however, because of unanswered questions on dose, duration, and effects on survival.
To explore these questions, Din and colleagues prospectively recruited 2,279 cases and 2,907 matched controls ages 16 to 79 years who completed a questionnaire on lifestyle, medications used and cancer history.
Analysis of the data determined that overall, the risk of colorectal cancer was lower in users of any NSAID compared with nonusers after adjustment for factors such as age, sex, and physical activity.
The inverse association between the use of 75 mg aspirin and colorectal cancer was seen for both men and women, but was significant only in men.
There was no protective effect of aspirin or NSAIDs on all-cause mortality during nearly five years of follow-up. Nor was there an effect on colorectal-related mortality.
The lack of effect on survival may relate to sample sizes or limited duration of intake, according to the researchers.
Among cases taking aspirin or NSAIDs there were 224 deaths, six possibly related to the drugs (one gastrointestinal bleed and five cerebrovascular accidents).
Among the cases not using aspirin or NSAIDs there were 486 deaths, with three bleeds and three cerebrovascular accidents.
There was no difference between users and nonusers in deaths resulting from bleeds, although power to detect a difference may have been inadequate.
Strengths of the study include its prospective design, matched controls, and its being representative of the population at large, not only high-risk groups.
A shortcoming was that the investigators were not aware if cases continued taking aspirin or NSAIDs after their cancer diagnosis, which limits the conclusions that can be drawn.
In addition, plasma levels of the drugs were not measured.
The authors noted that their results are applicable to the general population, and called for well powered randomized trials to further clarify the effects on survival.
Effect of aspirin and NSAIDs on risk and survival from colorectal cancer
1. Farhat V N Din1,
2. Evropi Theodoratou2,
3. Susan M Farrington1,
4. Albert Tenesa1,
5. Rebecca A Barnetson1,
6. Roseanne Cetnarskyj3,
7. Lesley Stark1,
8. Mary E Porteous4,
9. Harry Campbell2,
10. Malcolm G Dunlop1
+ Author Affiliations
1.Colon Cancer Genetics Group and Academic Coloproctology, Institute of Genetics and Molecular Medicine, University of Edinburgh and MRC Human Genetics Unit, Western General Hospital, Edinburgh, UK
2.Public Health Sciences, University of Edinburgh, Edinburgh, UK
3.Faculty of Life Sciences, Edinburgh Napier University, Craiglockhart Campus, Edinburgh, UK
4.Southeast of Scotland Clinical Genetic Services, Western General Hospital, Edinburgh, UK
1. Correspondence to Professor Malcolm G Dunlop, Colon Cancer Genetics Group and Academic Coloproctology, Institute of Genetics and Molecular Medicine, University of Edinburgh and MRC Human Genetics Unit, Western General Hospital, Edinburgh EH4 2XU, UK; firstname.lastname@example.org
* Revised 19 February 2010
* Accepted 15 March 2010
* Published Online First 15 September 2010
Background Previous studies have shown that aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) lower colorectal cancer (CRC) risk. However, the lowest effective NSAID dose, treatment duration, and effects on survival are not defined. In a large population-based case--control study, we have explored the relationship between NSAID dose and duration, CRC risk and overall CRC-specific survival.
Methods The relationship between NSAID use and CRC risk was examined in 2279 cases and 2907 controls. Subjects completed food-frequency and lifestyle questionnaires. NSAID categories were low-dose aspirin (75 mg), non-aspirin NSAIDs (NA-NSAIDs) and any NSAID. Users were defined as taking >4 tablets/week for >1 month. ORs were calculated by logistic regression models and adjusted for potential confounding factors. Effect of NSAID use on all-cause and CRC-specific mortality was estimated using Logrank tests and Cox's hazard models.
Results In all, 354 cases (15.5%) were taking low-dose aspirin compared to 526 controls (18.1%). Low-dose aspirin use was associated with decreased CRC risk (OR 0.78 95% CI 0.65 to 0.92, p=0.004), evident after 1 year and increasing with duration of use (ptrend=0.004). NA-NSAID and any NSAID use were also inversely associated with CRC. There was no demonstrable effect of NSAIDS on all-cause (HR 1.11, p=0.22, 0.94--1.33) or CRC-specific survival (HR 1.01, p=0.93, 0.83--1.23).
Conclusion This is the first study to demonstrate a protective effect against CRC associated with the lowest dose of aspirin (75 mg per day) after only 5 years use in the general population. NSAID use prior to CRC diagnosis does not influence survival from the disease.
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