Do you take an aspirin a day for aches and pains or other health reasons? It seems that many people do, and they might be inadvertently protecting themselves from cancer.
A Willow Tree Gave Us Aspirin:
The ancient Egyptians used the bark of the willow tree as a remedy for aches and pains. Hippocrates, the famous Greek physician (460-377 B.C.E.) used willow leaves and bark to treat pain and fevers. The active ingredient was not known until the 1800’s, when salicylic acid was isolated from the willow tree. Salicylic acid is also found in other plants, such as: jasmine, beans, peas, clover and certain grasses and trees.
The aspirin we use today is a less irritating form of salicylic acid (gentler on the stomach) called, acetylsalicylic acid (invented and commercialized by Bayer in the 1890’s.)
How Does Aspirin Reduce Cancer Risks?:
Figure 1: Aspirin mechanisms of action and pathophysiological effects. Black block arrows indicate known mechanisms. Dotted black arrows indicate potential mechanisms that could contribute to anti-cancer effects. Cox=cyclooxygenase; NFκB=nuclear factor-κB.
Aspirin has many anti-cancer effects, including encouraging precancerous/cancerous cell death (“apoptosis”), acting as a systemic anti-inflammatory agent, inhibiting the growth of tumor blood vessels and through a variety of other proposed mechanisms.
One recent study suggests that aspirin may slow down the rate in which normal cells accumulate mutations (called, somatic genome abnormalities).
This complicated figure (Figure 1) basically shows that aspirin combats cancer at the molecular level by beneficially modulating or suppressing the activity of the pro-inflammatory enzyme cyclooxygenase-2 (COX-2), the “master switch” protein complex nuclear factor-kappaB (NF-kB) and other anti-inflammatory pathways.
Read my previous blog post on the importance of reducing inflammation in helping to reduce the risk of cancer development, growth and progression.
Dr. Otis Brawley, chief medical officer of the American Cancer Society, has been quoted as saying, “Inflammation may not cause a cancer, but it may promote cancer — it may be the fertilizer that makes it grow.”
So, Show Me The Anti-Cancer Data…
Breast Cancer:
A study conducted in 2011 showed that women who took aspirin had about a 20% lower risk of breast cancer than non-users.
In another study, breast cancer survivors who took a daily aspirin were found to be less likely to have recurrence (43% risk reduction) and die (64% risk reduction) from the disease.
Colorectal Cancer:
Four large aspirin studies (analyzing populations of individuals who took aspirin versus those who did not) were combined into a single study (called a “meta-analysis”), and 14,033 new colorectal cancers were detected in this population after a follow-up of 18 years.
The researchers reported that by taking 75 mg of aspirin (similar to the amount in a ‘baby’ aspirin, also referred to as ‘low-dose’) for 5 or more years:
- The risk of developing colon cancer decreased by up to 70% and,
- The risk of developing rectal cancer decreased by 40%.
There was no added benefit of taking more than a single baby aspirin per day.
Numerous studies have shown that by taking a daily aspirin (81-325 mg per day), you can lower your risk of precancerous colon polyps by up to 28%. Since we know that colon cancer develops within these precancerous polyps (called “adenomas”), everything we do that can reduce the risk or number of polyps will reduce our risk of colorectal cancer.
If you have been diagnosed with colon cancer, taking an aspirin each day appears to increase your odds of survival. A recent study found that if your colon cancer expresses a common biomarker called HLA class 1 your odds of survival increase by 47% compared with those who do not take aspirin. In my opinion, this is study is of particular importance to patients at the highest risk of recurrence (stage 3).
Melanoma:
In a study of nearly 60,000 women, the women who used aspirin had a 21% lower risk of melanoma compared with non-users. The longer the women used aspiring the lower their risk:
- Aspirin use for less than 1 year: 11% lower risk than non-users
- Aspirin use for 1-4 years: 22% lower risk
- Aspirin use for 5 or more years: 33% lower risk
Ovarian Cancer:
In a study of 20,000 women, the investigators found that those who used aspirin daily had a 20% lower risk of ovarian cancer than those who used aspirin less than once a week.
Prostate Cancer:
In a study of 5,955 men, who received surgery or radiation therapy for prostate cancer, researchers found that the patients who reported that they regularly used aspirin (any dose) had a:
- 57% lower risk of dying from prostate cancer compared with non-users (after a 10-year follow-up)
- lower risk of having a prostate cancer recurrence
- lower risk of developing bone metastases from prostate cancer
Skin Cancer:
In a large observational study of postmenopausal women (59,000 women, followed for 12 years), researchers found that:
- Those who used aspirin had a 21% lower risk of melanoma compare with those who did not use aspirin.
- The longer the women took aspirin, the lower their risk for melanoma, with 11% reduced risk if they took it for one year, 22% reduced risk when taking it for between one and four years, and 30% risk reduction if taken for five years or longer.
Various Cancers:
In a large study (meta-analysis) that combined 8 trials (with over 25,000 patients) that randomized to receiving 4+ years of aspirin (75 mg per day) versus placebo, the researchers found that by taking aspirin for 4 years or more, the risk of dying from a variety of common cancers was significantly reduced. The benefit for cancer risk reduction was evident after only 5-years of follow-up. They found the following risk reduction in cancer deaths:
- prostate cancer (10% risk reduction)
- lung cancer (30% risk reduction)
- colon, rectal, pancreatic, and stomach cancers (40% risk reduction)
- esophageal and throat cancers (60% risk reduction)
The researchers suggest that the best time to start taking a low-dose baby aspirin would be in a person’s mid-40’s, the time when the risk of most cancers begins to rise significantly. There was no additional benefit for doses greater than 75 mg per day.
This graph demonstrates the beneficial effect of aspirin on incidence of cancer in the meta-analysis of the randomised trials of daily low-dose (75–100mg daily) aspirin versus placebo (control)
In another large study (meta-analysis) that randomized individuals to either a daily, low-dose aspirin (75-100 mg) or control (no aspirin), the researchers reported that aspirin use:
- reduced cancer deaths by 37% (when aspirin was taken daily for 5+ years)
- reduced the risk of developing cancer by 25% (when taken for 3+ years)
This study suggests that the anti-cancer benefits of aspirin start to appear as soon as 3 years after starting it (as you can see on the graph to the right, the blue arrow indicates that after 5 years the benefits of aspirin become much more obvious.)
The beneficial effects of aspirin in reducing risk of colorectal cancer show a substantial lag. Data are expressed as a fraction of reduced risk compared to untreated individuals (set at 0). Adapted from randomized controlled trials and observational studies.
Only recently have we begun to see more clearly how important it is to follow patients for a long time to see the benefits of taking a daily aspirin (following patients for a long time is critical for most prevention studies). For example, an analysis of various studies comparing aspirin use (75 mg per day) versus no aspirin use found that it takes about 5-years to before we see any anti-cancer benefit of aspirin. In this study, researchers show that by taking a low-dose, daily aspirin you are able to reduce your risk of developing colorectal cancers by 30% after 20 years.
Aspirin Use Reduces The Risk Of Cancer Spread (Metastases):
This graph shows the increasing risk (%) of being diagnosed with a cancer that has spread (metastasized) over time (years) after starting aspirin versus no aspirin (control.) Aspirin use reduced the risk of developing a cancer with a distant metastasis by 36%.
In a study (meta-analysis) that combined 5 trials (with over 17,000 patients) that randomized to receiving 75 mg per day of aspirin or not, investigators identified 987 new cancer (solid tumors) diagnoses.
- Aspirin use reduced the risk of being diagnosed with a cancer that has spread (metastasized) to distant parts of the body by 18-46% (greatest risk reduction with adenocarcinomas)
- Aspirin use reduced the risk of eventually developing a cancer metastasis, in patients who initially had no evidence of cancer spread, by 55%, by 74% (for colorectal cancers) and by 69% (for those with adenocarcinomas and still receiving aspirin at the time of or after their cancer diagnosis)
- Aspirin use reduced the risk of dying from cancer by 35%.
There was no added benefit for using higher doses than 75 mg per day. The risk reduction benefits of aspirin were even better in smokers.
Aspirin Reduces The Risk Of Colorectal Cancer In Individuals With Lynch Syndrome:
Time to first Lynch syndrome cancer in participants randomly assigned to aspirin compared with those assigned to aspirin placebo
Lynch syndrome is a genetic condition (also known as hereditary non-polyposis colon cancer or HNPCC) that carries a high-risk of developing colorectal and other cancers (i.e. endometrial, pancreatic, ureter, brain, small bowel, gastric, cholangiocarcinoma, kidney, ovarian.)
In a study of patients with Lynch syndrome, patients were randomized to receive either aspirin (600 mg per day) or placebo and were followed for over 10-years (mean: 4.6 years). The investigators reported that the daily use of aspirin significantly reduced the risk of developing all Lynch syndrome cancers by 35%.
The Bottom Line:
Facts:
- We don’t know which individuals will definitely benefit from the anti-cancer effects of aspirin.
- We don’t know how much we should recommend taking each day.
- We don’t know who is going to have side effects or complications from taking a daily aspirin.
So, what do I recommend?
For most healthy individuals, the risks of taking a daily, low-dose aspirin are low, and the potential anti-cancer benefits are significant. After weighing the pros and cons for each of my patients, more often than not, I think a low-dose, daily aspirin is a very reasonable preventive therapy for many of them.
If you are not currently taking a daily, low-dose (81 mg per day) aspirin but have been considering it, I recommend first discussing the potential risks and benefits with your health care team. Serious risks are uncommon but can be exacerbated (i.e. bleeding, stomach ulcers/gastritis, etc.) by co-existing medical problems as well as numerous medications.
Other References:
Can Aspirin Reduce Cancer Risk and Mortality? (U.S. National Cancer Institute)
Daily aspirin therapy: Understand the benefits and risks (Mayo Clinic)
Aspirin (U.S. National Institutes of Health)
Aspirin (WebMD)
The Everyday Drug That Prevents Cancer Death (Life Extension)
