Can Aspirin Prevent The Development of Colon Cancer and Cancer Recurrence?
by Dr. C.H. Weaver M.D. updated 5/2020
Women who take a low-dose aspirin every other day have a reduced risk of colon cancer. Thed most recent evidence supporting its use is the 18 year of follow-up in the Women’s Health Study, which was a 10-year randomized trial that evaluated the effects of aspirin and vitamin E on cardiovascular disease and cancer risk. The study included 35,876 women aged 45 or older with no history of cardiovascular disease or cancer. The women were randomly assigned to take 100 mg of aspirin or placebo every other day for 10 years. The extended follow-up includes data from 33,682 women.
Overall, there were 5,071 confirmed cancer cases (including 2,070 breast, 451 colorectal, and 431 lung). There were 1,391 cancer deaths. Women in the aspirin group had a 20 percent reduced risk of colon cancer, but the benefit didn’t appear until after a decade. What’s more, the aspirin group experienced a higher rate of gastrointestinal bleeding and peptic ulcers. There was no reduction in the overall risk of cancer or the risk of lung and breast cancer among women who took aspirin.
A recent review of several studies confirms that taking a small daily dose of aspirin significantly reduces the risk of developing – or dying from several kinds of cancer.(1-13) In order to study this further, researchers analyzed all the available evidence from studies and clinical trials evaluating taking aspirin daily for 10 years and confirmed that daily aspirin could reduce bowel cancer cases by around 35 percent and deaths from the disease by 40 percent. These results were published in the Annals of Oncology journal. (11)
Aspirin, originally developed by the German drug maker Bayer, is a cheap, over-the-counter drug generally used to combat pain or reduce fever. The drug when taking in smaller doses of 75-100 milligrams per day reduces the risk of clots forming in blood vessels and can therefore protect against heart attacks and strokes, so it is often prescribed for people who already suffer with heart disease and have already had one or several attacks.
The authors found that in addition to reducing the risk of developing colon cancer, the risk of esophageal and stomach cancer were cut by 30 percent and deaths from these cancers reduced by 35 to 50 percent. The authors of the current study observed that if everyone between 50 and 65 years of age started taking aspirin daily for at least 10 years, there would be a 9 percent reduction in the number of cancers, strokes and heart attacks overall in men, and around 7 percent in women.
There are however some serious side effects of aspirin including a risk of bleeding in the stomach. Among 60-year-olds who take daily aspirin for 10 years, the risk of digestive tract bleeding increases from 2.2 percent to 3.6 percent, and this could be life-threatening in a small proportion of people. The risk of bleeding has prevented some doctors from advising patients to take aspirin as regularly as every day. This risk of bleeding is well known and should not be ignored especially in individuals at high risk. In this era of wellness however where many individuals look to alternative medicines, nutritional supplements and foods rich in anti-oxidants, and other nutrients to reduce their caner risk an aspirin a day may be the simplest and most cost effective way to reduce the risk of gastrointestinal cancers.
Aspirin and Colon Cancer
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 multi-center 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.
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 non-polyposis 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 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.
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.
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 also 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.
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.
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)
What About BRAF?
Aspirin’s preventive effect for colorectal cancer may be limited to tumors without a genetic mutation known as BRAF, according to the results of a study published in the Journal of the American Medical Association. About 10 percent of colorectal cancers have a mutated BRAF gene. Studies have shown that BRAF mutations confer a poorer prognosis in colorectal cancer and also may predict a poorer response to targeted agents known as EGFR inhibitors.
Researchers evaluated data from two large observational studies—the Nurses’ Health Study and the Health Professionals Follow-up Study—to examine the relationship between aspirin use and BRAF tumor status. The two studies combined included data from 128,000 participants—and both studies had follow-up data on cancer incidence through July 2006 and on cancer mortality through 2011. Data in the studies also included tumor genotype status for participants.
During follow-up, there were 1,226 cases of colorectal cancer, of which 182 involved the BRAF mutation. Overall, there was a lower rate of colorectal cancer among the daily aspirin users. What’s more—there appeared to be a dose-response effect: among participants who took two to five aspirin tablets per week, there was only a trend toward reduced cancer risk, whereas among those who took more than 14 tablets per week, the cancer risk was cut by 50 percent.
However, it appears this risk reduction was limited to those without the BRAF mutation. When researchers compared those with wild-type BRAF (no mutation) and those with a BRAF mutation, they found that those with the mutation did not appear to receive the same preventive effect from aspirin. The researchers concluded that regular daily aspirin use was associated with a lower risk of colorectal cancer without the BRAF mutation, but not with BRAF-mutated colorectal cancer. They speculate that “BRAF-mutant colon tumor cells may be less sensitive to the effect of aspirin.”
- 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.
- Cuzick J, Thorat MA, Bosetti C. et al. Estimates of benefits and harms of prophylactic use of aspirin in the general population. Annals of Oncology. 10,2014 doi:10.1093/annonc/md
- Burn J, Gerdes A-M, Macrae F et al. Long-term effect of aspirin on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised controlled trial. Lancet. Early online publication October 28, 2011.
- Tan X-L, Reid Lombardo KM, Bamlet WR, Robinson DP, Anderson K, Petersen GM. Aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen and risk of pancreatic cancer. Presented at the 102nd Annual Meeting of the American Association for Cancer Research (AACR), April 2-6, 2011, Orlando, FL. Abstract 1902.
- Nishihara R, Lochhead P, Kuchiba A, et al. Aspirin Use and Risk of Colorectal Cancer According to BRAF Mutation Status. JAMA. 2013; 309(24): 2563-2571.
- Cook NR, Lee IM, Zhang SM, et al. Alternate-day, low-dose aspirin and cancer risk: Long-term observational follow-up of a randomized trial. Annals of Internal Medicine. 2013; 159(2): 77-85.
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