Colorectal cancer is the second leading cause of cancer-related deaths in the United States. Research studies have shown that aspirin can decrease the incidence of colon polyps, prevent pre-cancerous lesions from developing and reduce the risk of colorectal cancer recurrence following treatment. Here is what the research shows....
Aspirin Helps Prevent Colorectal Adenomas
Several clinical trials have reported that regular use of aspirin appears to reduce the risk of developing colorectal adenomas.
The first trial was conducted by researchers affiliated with the Cancer and Leukemia Group B (CALGB) to evaluate aspirin intake in over 630 patients previously diagnosed with colorectal cancer. All of these patients had undergone the surgical removal of their cancer.(1) Patients received either 325 milligrams per day of aspirin or a placebo (inactive substitute) and were followed up with colonoscopy screening.
In the group of patients receiving aspirin, only 17% developed one or more adenomas, compared to 27% in the group of patients receiving placebo. Furthermore, the development of adenomas occurred later in the group of patients receiving aspirin.
The second trial was a large multicenter trial headed by researchers from the Norris Cotton Cancer Center in New Hampshire.(2) This trial involved approximately 1,120 patients diagnosed with an average of approximately 2 colorectal adenomas. Patients were randomly selected to receive low-dose aspirin (81 mg), normal-dose aspirin (325 mg) or placebo (inactive substitute) and were followed up with colonoscopy screening at one and two years following initiation of the trial.
The development of at least one adenoma during the trial occurred in 38.3% of patients treated with low-dose aspirin, 45.1% of patients treated with normal-dose aspirin and 47.1% of patients treated with placebo. These researchers concluded that daily aspirin, especially low-dose aspirin, has moderate preventive effects on the development of adenomas in patients previously diagnosed with colorectal adenomas.
Researchers performed a meta-analysis on the data from all randomized, double-blind, placebo-controlled trials that have evaluated the use of aspirin for the prevention of colorectal adenomas. The data included four clinical trials with a total of 2,967 participants; these participants received 81-325 mg of aspirin per day. Among 2,698 participants who underwent colonoscopic follow-up after randomization, adenomas were found in 37% of those allocated to placebo and in 33% of those allocated to any dose of aspirin (advanced lesions were found in 12% and 9%, respectively).(3)
The available research clearly suggests that aspirin is effective for the prevention of colorectal adenomas. Patients previously diagnosed with colorectal cancer or colorectal adenomas should to discuss the risks and benefits of taking daily aspirin with their physician. However, since the use of aspirin carries its own risks, it is important for patients to discuss taking aspirin with their physician.
Aspirin May Reduce The Risk of Developing Colorectal Cancer
Research also suggests that aspirin can reduce the risk of developing colorectal cancer.(4,5)
To evaluate the relationship between aspirin and other NSAID use and the risk of colorectal cancer, researchers analyzed data from a study of over 82,000 nurses. The nurses provided information about their medication use every two years starting in 1980. Over a period of 20 years, 962 of the nurses developed colorectal cancer. The lowest risk of colorectal cancer was observed among women who had taken more than 14 standard (325 mg) aspirin tablets per week for more than 10 years. These women had roughly half the risk of developing colorectal cancer as women who did not regularly use aspirin. Fewer women were regular users of other NSAIDS, but high doses of other NSAIDS appeared to produce a similar reduction in colorectal cancer risk. Among women who regularly used acetaminophen (a pain reliever that is not an NSAID), there was no reduction in risk of colorectal cancer.
The researchers conclude that regular long-term aspirin use reduces the risk of colorectal cancer. Use of nonaspirin NSAIDS also appears to reduce the risk of colorectal cancer.
While studies have suggested that use of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen may help protect against colorectal cancer. These studies, however, haven’t determined the lowest possible effective dose for colorectal cancer prevention or how long aspirin or other NSAIDs must be used to have a protective effect.
Twenty-year follow-up data from over 14,000 individuals indicate that daily doses of 75 mg or more of aspirin taken for five or more years reduces the long-term incidence and mortality of colorectal cancer. (5)
The study evaluated patient data from four randomized trials in order to determine the preventive effect of aspirin on colorectal cancer over 20 years. Patients enrolled in these trials were randomized to either receive aspirin or not to receive aspirin. Average duration of scheduled treatment was six years.
- Patients who received aspirin were less likely to develop colon cancer during 20 years of follow-up “with a latent period of 7-8 years between aspirin intake and its preventive effect.”
- Patients taking aspirin for five years or more appeared to benefit the most with a 70% reduction in risk of developing proximal colon cancer, which is in the upper bowel.
- Doses of aspirin above 75 mg daily did not demonstrate an improvement in risk reduction of developing colorectal cancer; however, doses of 30 mg daily appeared to be less effective.
The researchers concluded that 75 mg daily (or more) of aspirin taken for five years or more reduced the long-term risk of developing and dying from colorectal cancer. Individuals may wish to speak with their physician regarding the risks and benefits of daily aspirin use for reducing the risk of colorectal cancer.
Among people with Lynch Syndrome, daily aspirin use may cut the risk of colorectal cancer in half.
Lynch Syndrome, also known as hereditary nonpolyposis colorectal cancer (HNPCC), results from inherited mutations in genes involved in DNA mismatch repair. These mutations greatly increase the risk of developing colorectal cancer. In individuals with Lynch Syndrome, the average age at diagnosis of colorectal cancer is about 44 years, compared with 64 years in the general population. Overall, roughly 3% to 5% of all colorectal cancers are thought to result from Lynch Syndrome. Research suggests that in individuals with Lynch Syndrome
- Daily aspirin reduced the risk of colorectal cancer by 44%.
- In the subset of study participants who took aspirin for at least two years, the risk of colorectal cancer was reduced by more than half.(6)
Aspirin May Prevent Colon Cancer Recurrence After Treatment
Research also suggests that colorectal cancer patients treated with surgery and chemotherapy, experience less recurrence's and fatalities with regular aspirin use.
According to the results of a study recently reported in the Journal of the National Cancer Institute, patients with stage III colon cancer who take aspirin or other agents that inhibit cyclooxygenase-2 near the time of adjuvant chemotherapy appear to have a lower risk of cancer recurrence.
It has long been suggested that aspirin and COX-2 inhibitor use may be associated with improved outcomes in the management of early stage colon cancer patients based on analyses of observational clinical studies.
In the current study, investigators analyzed data from patients enrolled in a Cancer and Leukemia Group B study that previously compared different chemotherapy treatment regimens for stage III colon cancer. Overall, 9.4% of patients with relevant data were aspirin users and 7.0% were users of COX-2 inhibitors. Users were defined as individuals reporting to use both during and 6 months after chemotherapy.
With a median follow-up of 6.5 years, users relative to nonusers of either COX-2 inhibitors or aspirin were more likely to delay cancer recurrence and experience longer survival. Analyses also suggested a possible dose-response relationship for aspirin, whereby benefit increased with weekly dose. Neither medication class was associated with an increased risk of cardiovascular events or other side effects.
While the exact dose and duration of aspirin or COX-2 inhibitors required for a potential protective effect in the management of colon cancer remains unclear, this analysis of colon cancer patients enrolled in a chemotherapy clinical trial supports a benefit for aspirin use in individuals with colorectal cancer.
CALGB 80702 and ASCOLT are two ongoing trials currently being performed which evaluate the role of celecoxib and aspirin, respectively, in colon cancer. Individuals undergoing chemotherapy for the treatment of colon cancer should discuss the potential risks and benefits of taking concomitant aspirin with their treating physician. Many individuals can certainly benefit from daily aspirin for other reasons; however, some individuals, particularly those with various gastrointestinal conditions, may have their condition worsened with aspirin. Patients should always make their doctor aware of any non-prescribed medicines or supplements they are taking.(10)
Researchers have alsor evaluated 830 patients with stage III colon cancer from another study evaluating two different chemotherapeutic regimens. It was determined that 8.7 percent of these patients were regular aspirin users. Analysis revealed that 72 of the 830 patients consistently used aspirin during and after treatment and a comparison of this group with non-aspirin users determined that consistent aspirin use was associated with a significant reduction (48 percent) in the risk of colorectal cancer disease recurrence and death. It was additionally noted that consistent users of COX-2 inhibitor drugs (Celebrex®, Vioxx®) had similar results, while users of acetaminophen (Tylenol®) did not.(7)
Another study evaluated the effects of aspirin in 1,279 men and women diagnosed with Stages I –III colorectal cancer. The doctors found that after a median follow-up of almost 12 years, the death rate was 35% among aspirin users and 39% among non-aspirin users. The cancer-specific death rate was 15% for aspirin users and 19% for non-aspirin users. In patients whose primary tumor over-expressed COX-2, regular aspirin use was associated with a 61% reduction in the cancer-specific death rate.(8)
Aspirin use after a colorectal cancer diagnosis is associated with a lower risk of cancer-specific and overall mortality, especially in patients with tumors that over-express the COX-2 enzyme.
Aspirin May Prolong Life in PIK3CA-Mutated Colorectal Cancers
The phosphatidylinositol 3-kinase (PI3K) signaling pathway plays a significant role in carcinogenesis. Approximately 15 to 20 percent of colorectal cancers carry a PIK3CA mutation. There is some evidence that aspirin may suppress cancer growth by blocking the PI3K pathway.
Researchers from Massachusetts analyzed data from 964 patients from two large prospective cohort studies—the Nurses’ Health Study and the Health Professionals Follow-up Study. They noted the patients’ PIK3CA mutation status and aspiring use after being diagnosed and found that those with the mutation gained a survival benefit with daily aspirin use. Among patients with PIK3CA mutations, five years after diagnosis, 97 percent of those taking daily aspirin were still alive, compared to 74 percent of those not taking aspirin. In contrast, aspirin had no impact on five-year survival rates among patients without the mutation.
The researchers concluded that daily aspirin use after diagnosis was associated with longer survival among patients with PIK3CA mutations, but not those without the mutation. These results suggest that the PIK3CA mutation could serve as a predictive biomarker for aspirin therapy. Larger studies will be needed to verify these results—but for now it appears that patients with the PIK3CA mutation might benefit from aspirin use. Other patients may choose to use aspirin as well; however, it could be less effective and sometimes leads to gastrointestinal ulcers and stomach bleeding.(9)
- Sandler RS, Halabi S, Baron JA, et al, A Randomized Trial of Aspirin to Prevent Colorectal Adenomas in Patients with Previous Colorectal Cancer. New England Journal of Medicine. 2003;348:883-890.
- Baron JA, Cole BF, Sandler RS, et al, A Randomized Trial of Aspirin to Prevent Colorectal Adenomas. New England Journal of Medicine. 2003;348:891-899.
- Cole BF, Logan RF, Halabi S, et al. Aspirin for the chemoprevention of colorectal adenomas: Meta-analysis of the randomized trials. Journal of the National Cancer Institute. 2009; 101:256-266.
- Chan AT, Giovannucci EL, Meyerhardt JA et al. Long-term use of aspirin and nonsteroidal anti-inflammatory drugs and risk of colorectal cancer. JAMA. 2005;294:914-923.
- Rothwell PM, Wilson M, Elwin C-E, et al. Long-term effect of aspirin on colorectal cancer incidence and mortality: 20-year follow-up of five randomised trials. The Lancet [early online publication]. October 22, 2010.
- Burn J, Bishop T, Mecklin JP, et al. Effect of aspirin or resistant starch on colorectal neoplasia in the lynch syndrome. New EnglandJournal of Medicine. 2008; 359: 2567-2578.
- Chan AT, Ogino S, Fuchs CS, et al. Aspirin use and survival after diagnosis of colorectal cancer. Journal of the American Medical Association. 2009; 302: 649-658.
- Fuchs C, Meyerhardt d, Helseltine K, et al. Influence of regular aspirin use on survival for patients with stage III colon cancer: Finding from Intergroup trial CALGB 89803. American Society of Clinical Oncology 2005; Abstract #3530.
- Liao X, Lochhead P, Nishihara R, et al. Aspirin use, tumor PIK3CA mutation, and colorectal-cancer survival. New England Journal of Medicine. 2012; 367: 1596-1606.
- Ng K, Meyerhardt J, Chan A, et al. Aspirin and COX-2 Inhibitor Use in Patients With Stage III Colon Cancer. Journal of National Cancer Institute. (2015) 107 (1): dju345 doi: 10.1093/jnci/dju345.