Excluding skin cancers, colorectal cancer is the third most common cancer in women and men in the United States. The American Cancer Society’s estimates for the number of colorectal cancers in the United States for 2023 are:

• 106,970 new cases of colon cancer
• 46,050 new cases of rectal cancer

The rate of colorectal cancer diagnoses has dropped annually since the mid-1980s, largely because more people are getting screened and changing lifestyle-related risk factors.

Colorectal Cancer is Rising Among the Young

From 2011 to 2019, colorectal cancer incidence rates dropped by about one percent annually. However, this downward trend is mostly in older adults. For those under 50, rates have been increasing by one to two percent each year since the mid-1990s.

Colorectal cancer is a significant health concern worldwide, accounting for many cancer-related deaths. As researchers continue to investigate potential preventive strategies, one intriguing area of study is aspirin.

While we lack sufficient data to recommend aspirin to reduce colorectal cancer risk routinely, a new study is encouraging.

Aspirin, a widely available non-steroidal anti-inflammatory drug (NSAID), has been the subject of numerous studies examining its potential role in reducing the risk of colorectal cancer.

This essay delves into the relationship between aspirin use and the risk of colorectal cancer, exploring the evidence, mechanisms, and potential benefits of this medication.

Aspirin and Colorectal Cancer — Background

Multiple studies have suggested a potential link between aspirin use and a reduced risk of developing colorectal cancer. The evidence originates from observational studies and randomized controlled trials.

First, observational studies (such as the Nurses’ Health Study and the Health Professionals Follow-up Study) show a consistent association between long-term aspirin use and a reduced incidence of colorectal cancer.

Second, a meta-analysis published in The Lancet in 2010 found a one-quarter (24 percent) reduction in colorectal cancer incidence among individuals who took aspirin regularly.

How Might Aspirin Reduce Colorectal Cancer Risk?

We have not yet fully elucidated the mechanisms by which aspirin might reduce colorectal cancer risk. There are likely several biological pathways.

For example, aspirin exerts anti-inflammatory effects by blocking the cyclooxygenase (COX) enzymes, especially COX-1 and -2. These enzymes are critical to prostaglandin production, substances known to promote inflammation and cancer development.

Aspirin inhibits COX enzymes, dropping prostaglandin production and attenuating the inflammatory response.

Aspirin — Cancer and Cardiovascular Benefits?

While the evidence suggests a potential protective effect of aspirin against colorectal cancer, it is important to consider the benefits and the potential risks associated with its use.

Aside from reducing the incidence of colorectal cancer, aspirin has also been linked to a lower risk of other gastrointestinal cancers, including the esophagus, stomach, and pancreas.

Additionally, aspirin has well-established cardiovascular benefits, including preventing heart attacks and strokes, further enhancing its potential value.

However, it is important to acknowledge the potential risks of aspirin use, such as gastrointestinal bleeding and hemorrhagic stroke. These risks tend to increase with higher doses and long-term use.

Therefore, individuals considering aspirin for colorectal cancer prevention should consult their healthcare providers to evaluate their risk factors and discuss the potential benefits and risks.

Colon Polyps and Adenomas

A colon polyp is a small clump of cells that forms on the colon’s lining. Most colon polyps are harmless. But over time, some colon polyps can develop into colon cancer. Colon cancer can be fatal when found in its later stages.

Anybody can develop colon polyps. The risk is higher for those 50 or older. Smokers and overweight individuals also have a higher risk. Those with a personal or family history of colon polyps or colon cancer also are at higher risk of developing a polyp.

Colon polyps don’t usually cause symptoms. It’s important to have regular screening tests because the doctor can usually remove early colon polyps safely and completely. The best prevention for colon cancer is regular screening for and removing polyps.

Adenomas are non-cancerous tumors. Tubular adenomas are pre-cancerous polyps in your colon (or rectum), typically found during colonoscopies. Such polyps are your body’s early warning system for colorectal cancer. While approximately half of us will develop tubular adenomas, less than one in ten tubular adenomas, become cancer.

Aspirin and Colorectal Cancer — A New Study

Aspirin is a compelling research area in the context of colorectal cancer risk reduction. A new study assessed the association between regular aspirin or NSAID (non-steroidal anti-inflammatory drugs such as ibuprofen) use at least twice weekly with the risk of developing early-onset adenoma.

A new study demonstrates the following:

Regular use of aspirin or other nonsteroidal anti-inflammatory drugs was associated with a lower risk of early-onset conventional and advanced adenomas.

The researchers explain that aspirin could be an effective strategy in preventing early-onset colorectal cancer.

One of the study authors, Dr. Cassandra Fritz of Washington University (USA), offers a “15 percent reduction for all adenomas and a one-third drop for those with more concerning forms of adenoma.

The analysis focused on data from the Nurses’ Health Study II. The study included more than 32,000 women with at least one colonoscopy before age 50 (1991–2015).

For the clinicians amongst you: High-risk adenomas included those at least one centimeter with tubulovillous/villous histology or high-grade dysplasia or at least three adenomas.

Aspirin Risks: The Drug is Not for Everyone

For selected individuals, daily aspirin is helpful to lower heart attack, clot-related stroke, and other blood flow risks in patients with cardiovascular disease or who have already had a heart attack or stroke. Many medical professionals prescribe aspirin for these uses.

There may be a benefit to daily aspirin use if you have some kind of heart or blood vessel disease or if you have poor blood flow to the brain. However, long-term aspirin use risks may be greater than the benefits if there are no signs of, or risk factors for, heart or blood vessel disease.

The US Food and Drug Administration (FDA) reminds us that every prescription and over-the-counter medication has risks and benefits — even aspirin, a common medicine. Aspirin can cause serious toxicities, such as brain or stomach bleeding and kidney failure.

No medicine is completely safe. By carefully reviewing many factors, your health professional can help you make the best choice.

Please Don’t Forget Colorectal Screening

Colorectal cancer screening plays a crucial role in the early detection and prevention of one of the most common types of cancer worldwide.

Colorectal cancer is highly treatable when caught early. However, it often develops without noticeable symptoms in its initial stages, underscoring the significance of regular screening.

Screening for colorectal cancer is recommended for both men and women starting at the age of 45 or earlier for individuals with a family history of the disease or other risk factors.

Various screening methods are available, including colonoscopy, sigmoidoscopy, fecal occult blood tests (FOBT), and fecal immunochemical tests (FIT).

Colorectal Cancer Screening Benefits

These screening tests help identify precancerous polyps or early-stage cancers that may not yet be causing symptoms. Detecting and removing these abnormal growths during screening can significantly reduce the risk of developing colorectal cancer.

Regular colorectal cancer screening has several important benefits. Firstly, it reduces mortality rates by detecting cancer early when it is more treatable. Early detection often leads to less invasive treatment options, higher survival rates, and better patient outcomes.

Secondly, screening can help identify and remove polyps before they become cancerous, preventing colorectal cancer altogether. This observation highlights the preventive aspect of screening, as it can potentially eliminate or catch the disease at its most treatable stage.

Lastly, screening can provide peace of mind for individuals by assuring them that their colorectal health is being monitored and any issues can be addressed promptly.

Regular screening, combined with a healthy lifestyle that includes a balanced diet, regular exercise, and avoidance of known risk factors such as smoking and excessive alcohol consumption, significantly contributes to the overall prevention and early detection of colorectal cancer.

Here are the US Preventative Services Task Force guidelines:

Colorectal Cancer: Screening Guidelines

www.uspreventiveservicestaskforce.org

Key points — Unveiling the Power of Aspirin: Game-Changer for Colon Cancer Prevention?

Question. Does aspirin have the potential to be a game changer for colon cancer prevention?

Findings. A new study shows that the regular use of aspirin or other nonsteroidal anti-inflammatory drugs is associated with a lower risk of early-onset conventional and advanced adenomas.

Meaning. While confirmatory research is needed, the one-seventh (15 percent) reduction with aspirin/NSAIDS in early-onset adenoma — and particularly for the quite substantial one-third risk-reduction in advanced adenoma with advanced histology, we need to think about a precision-based chemoprevention strategy for early-onset precursors of colorectal cancer.

This study does not give us high-level evidence to recommend aspirin for all. Individuals at high risk for colorectal cancer should consult an expert healthcare provider. Of course, screening remains a cornerstone of reducing our risk of dying from colorectal cancer.

The US Food and Drug Administration reminds us that if you use aspirin daily to prevent a heart attack, stroke, or any use not listed on the label — without guidance from your health professional — you could be doing your body more harm than good.

Potential conflicts. One of the study authors (Dr. Cao) consults for Geneoscopy, a non-invasive colorectal cancer screening company.

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But is the message that simple? Even though multiple cancer-related organizations spread the message that obesity increases cancer risk, we based the observation on imperfect observational studies.

Still, the American Cancer Society offers that being overweight or obese is associated with an increased risk of several cancer types, including:

• Breast cancer (in women past menopause)
• Colorectal cancer
• Esophagus cancer
• Gallbladder cancer
• Kidney cancer
• Liver cancer
• Ovarian cancer
• Pancreas cancer
• Stomach cancer
• Thyroid cancer
• Uterus (endometrial) cancer
• Myeloma
• Meningioma (a tumor of the brain or spinal cord lining)

Being overweight or obese might also raise the risk of other cancers, such as:

• Malignant (Non-Hodgkin) lymphoma
• Male breast cancer
• Mouth, throat, and voice box cancers
• Aggressive forms of prostate cancer

A new study suggests that excessive weight may be causally related to only six types of cancer. Let’s explore this new research, but first, we need to talk about a statistical maneuver known as Mendelian randomization.

Mendelian randomization

How can we examine the relationship between obesity and cancer? Mendelian randomization is a novel epidemiological tool developed over the last two decades, in large part because of the vast quantity of data emerging from genome studies.

With the technique, we can examine the causal effects of a modifiable exposure on disease in observational studies. We will see the increasing use of Mendelian randomization in the future as genetic knowledge of health and disease expands from gene sequencing.

Mendelian randomization can suggest a causal relationship between a risk factor (such as body weight) and disease outcome (for example, cancer incidence). MR uses genetic data as a “proxy” for non-genetic information. This approach allows us to test for causal effects when confounding variables are present.

The downside? Mendelian randomization studies are not actual experiments and rely on some assumptions. We still need to fall back on high-level evidence, such as from randomized clinical trials in this context.

Weight and cancer: New study results

With the brief primer on statistics behind us, let’s turn to a 2022 study based on Mendelian randomization. For the study, Dr. Fang and colleagues reviewed 204 meta-analyses and discovered “strong evidence” pointing to an association between obesity and 11 cancers.

These 11 cancers include esophageal adenocarcinoma, multiple myeloma, and cancers of the gastric cardia, colon, rectum, biliary tract system, pancreas, breast, endometrium, ovary, and kidney.

But, while the associations may be causal for some cancers, there can be confounding with numerous other risk factors. The researchers turned to Mendelian randomization studies examining the association between genetic variants linked to body mass index to get around this problem.

Here are the new findings of the Mendelian randomization studies:

There is a causal relationship between obesity and six cancer types: colorectal, endometrial (uterus), ovarian, kidney, pancreas cancer, and esophageal adenocarcinoma.

In addition, these studies further establish the inverse relationship between early-life obesity with breast cancer. I would note that post-menopausal weight gain is associated with a higher risk of breast cancer.

The new research approach did not link obesity and gallbladder and stomach cardia (the part closer to the esophagus), cancer, and multiple myeloma.

The new research approach did not link obesity and gallbladder and stomach cardia (the part closer to the esophagus), cancer, and multiple myeloma.

For six cancer types for which a causal relationship with obesity could be established, the effect estimates from the Mendelian randomization studies were more robust than those seen in conventional studies. The magnitude of risk ranged from 1.14-fold for early-life obesity and breast cancer to 1.37-fold for adult obesity and esophageal adenocarcinoma.

This study reminds us of a need for those in the United States and elsewhere to develop strategies to drop childhood, adolescent, and adult obesity.

The Breast Cancer Research Foundation supports one of the study authors. The researchers report no other relevant financial relationships.

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