NON-STEROIDAL ANTI-INFLAMMATORY DRUGS ARE ASSOCIATED WITH REDUCED CANCER RISK AND MORTALITY

Medically Reviewed by Dr. Sony Sherpa, (MBBS) - October 01, 2024

In the quest for better treatment options and improved disease outcomes, scientists have discovered that many common prescriptions have additional effects over and above their intended use. Over-the-counter painkillers, known as NSAIDs, have recently hit the oncological spotlight due to their hidden anticancer properties.

The below article takes a brief look at NSAIDs and how they may help to lower the risk of contracting various types of cancer.

Benefits of NSAIDs for Cancer Prevention and Prognosis

Research from recent years has linked NSAID use with the following cancer-related benefits:

Lowers Risk of Contracting Several Cancer Types

When reviewing a few common types of cancer in connection to NSAIDs, it becomes apparent that their use can reduce the overall risk of cancer. However, this effect does not extend equally to all types of cancer, as shown below.

• Colon Cancer. NSAID use has shown the most promise in preventing colon cancer. One study showed that daily NSAID use was nearly as effective as high dietary fiber intake for reducing the incidence of colorectal growth abnormalities (polyps) upon screening. Despite this, daily use is not free from side effects, as explained below. According to a study, monthly NSAID use proved to be nearly as effective as daily use.^[1] Other studies have confirmed that daily NSAID use reduced the risk for colon and rectal cancers.^[2]
• Head and Neck Cancer. A meta-review showed that non-aspirin NSAIDs may reduce the risk of acquiring head and neck cancers by as much as 13%^[3].
• Brain Tumours. While there is limited evidence, NSAIDs are associated with a reduced risk for CNS tumors, specifically gliomas and glioblastomas. Meningioma risk was unaffected by NSAID use.^[4]
• Lung Cancer. Non-aspirin NSAIDs were shown to provide a very small protective benefit against lung cancer^[5]. Despite this, aspirin may elevate the risk, especially for small-cell lung carcinomas^[6].
• Breast Cancer. In a large sample of over 50,000 women, breast cancer risk was seen to be reduced in premenopausal women who frequently took aspirin and other NSAIDs^[7]. These women took at least one NSAID per week for the course of a year. The results did not extend to menopausal and postmenopausal women.
• Other Reproductive Cancers. As seen in breast cancer, NSAIDs were shown to be protective against aggressive prostate cancers^[8] and endometrial cancer^[9]. Aspirin proved to lower the risk for cervical cancer more than other NSAIDs.^[10] Low-dose aspirin may be protective against ovarian cancer^[11]. Other studies suggest there is no association between NSAIDs and the risk for either ovarian or endometrial cancer.^[12] Due to conflicting results, more research is required to ascertain if NSAIDs are protective against female reproductive cancers or not.
• Skin Cancer. NSAID use shows contradictory results with respect to preventing melanoma.^[13] Aspirin and ibuprofen may reduce risks pertaining to basal cell carcinomas, while coxibs may offer a small protective benefit against squamous cell carcinomas.^[14]

May Enhance Treatment Efficacy

Shown to Inhibit Metastasis and Lower Metastatic Risk. In a large-scale review of over 200,000 cancer patients, NSAID use was associated with a significantly reduced risk of metastasis for selective types of cancer, including breast and prostate cancers. These results were noted to be equitable irrespective of NSAID use before or after a diagnosis was made^[15]. In vitro studies confirm these results by revealing that aspirin has the ability to inhibit circulating tumor cells from becoming metastatic tumors.^[16]

Reduces Risk of Recurrence After Surgery. One review discovered that NSAIDs help to improve prognosis in cancer patients post-surgery. Those who made use of NSAIDs for pain management after cancer surgery tended to have a reduced risk for recurrence and a longer time till recurrence.^[17] Despite lowering the risk for cancer, metastases, and recurrence, there are conflicting results with respect to enhancing survival outcomes.^{[18] [19]}

How NSAIDs Work to Lower Cancer Risk and Enhance Prognosis

NSAID Mechanism of Action. NSAIDs are mainly prescribed to block pain, inflammation and fever, although they are also known to have a blood thinning effect. The underlying mechanism pertains entirely to their select ability to inhibit the cyclooxygenases, COX-1 and COX-2. These are enzymes responsible for initiating the production of prostaglandins, which contribute to certain types of inflammation, the pain response and fever. COX-2 is especially known for enabling these symptoms, while COX-1 is involved in blood coagulation, which is why NSAIDs are able to thin the blood through lowering platelet activation via this pathway.

Faulty Wound Healing and Carcinogenesis Risk. Under usual circumstances, inflammation and the pain response are required to initiate wound healing. COX-2 and its associated prostaglandins are known to stimulate regenerative cell migration, proliferation, blood vessel growth and cell adhesion. However, this has been shown to promote the growth of specific types of tumors as well. Excessive activation of COX-2 is linked with excessive inflammation and an elevated risk for both cancer and metastases. In this respect, NSAID use can minimize the risk by inhibiting COX-2, particularly with respect to gastrointestinal cancers, prostate and breast cancer, as well as lung cancer.

Other Potential Anticancer Benefits. NSAIDs have proven to help induce death in tumor cells while promoting survival in healthy cells through mechanisms other than COX-1 and COX-2 inhibition. This anticancer benefit has been linked to NSAIDs’ ability to activate receptors and other cellular pathways that are involved in regulating growth and metabolism.^{[20] [21]} These pathways are known to exert other kinds of useful anti-inflammatory effects, which can further contribute towards inhibiting cancer-causing gene switches and lowering the risk of contracting some forms of cancer. Other studies suggest that NSAIDs may improve immune detection of colorectal cancer cells through lowering inflammation and promoting proteins associated with faulty cell death^[22].

Infrequent NSAID Use May Be the Best Prevention Measure. Despite this understanding, excessive NSAID use can contribute to other health issues and may equally detract from the optimal regeneration of wounded tissues. As reflected above, studies suggest that using an NSAID once a month may be nearly equitable to daily use with respect to cancer prevention.

NSAID Types and Chemo Efficacy. While frequent NSAID use may prove to be more beneficial for helping those already diagnosed with cancer, more research is required to confirm the efficacy across different types of NSAIDs as well as dosing. Preliminary studies suggest a difference between concerning aspirin and non-aspirin NSAIDs, with either category capable of lowering cancer risk in different body tissues. Aspirin has been linked with increased mortality rates in elderly patients with late-stage cancer^[23], while other NSAIDs may enhance treatment outcomes in this population^[24]. The outcomes are likely to be affected by differences in overall health status, comorbid disease, liver drug metabolism, and polypharmacy interactions, which requires further research to clarify.

Conclusion

While NSAIDs are commonly prescribed for lowering pain and the severity of fever, they may become a popular medication for improving the prognosis of cancer patients in the future. Lifetime NSAID use is linked with a lower risk of contracting many types of cancer, particularly those of the breast, prostate, digestive tract and lungs. Due to lower recurrence and metastasis rates in cancer patients that make use of NSAIDs for pain management, NSAIDs may become standard complementary therapeutics to chemo. More research is required to establish the efficacy of different types and quantities of NSAIDs with respect to various cancer cell lines.

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