DNA strand intertwined with a colon.

The Gut Gene Gamble: Does UGT1A1 Hold the Key to Colorectal Cancer?

Kai Mendoza in Health & Wellness August 2025 • 5 min read.

"Unlocking the Secrets of Genetic Variations and Colorectal Cancer Risk"

Colorectal cancer (CRC) is a major health concern, ranking as the third most common cancer in men and the second in women worldwide. While factors like age, family history, diet, and lifestyle choices are known to influence CRC risk, the role of genetics is increasingly under the spotlight. One gene of particular interest is UGT1A1, which plays a crucial role in how our bodies process and eliminate potentially harmful substances.

The UGT1A1 gene is responsible for producing an enzyme that helps to detoxify various compounds, including some that can contribute to cancer development. However, not all UGT1A1 genes are created equal. Variations in the gene, known as polymorphisms, can affect how efficiently the enzyme works. One common polymorphism, called UGT1A128, involves a difference in the number of repeated DNA sequences within the gene's promoter region. This seemingly small change can impact the amount of enzyme produced, potentially altering an individual's risk of developing CRC.

This article delves into a study that investigated the association between the UGT1A128 variant and the characteristics of colorectal cancer. By examining a group of patients with CRC, researchers aimed to determine whether carrying the UGT1A128 variant influences the development of precancerous lesions or specific traits of colorectal tumors. Understanding this connection could refine screening strategies, personalize treatment approaches, and ultimately improve outcomes for individuals at risk of or affected by colorectal cancer.

Decoding UGT1A1: How Gene Variations Influence Colorectal Cancer

The study examined patients treated for colorectal cancer, focusing on the UGT1A128 variant, which has seven TA repeats (TA)7, compared to the most common allele (TA)6. The key question was whether having the (TA)7/(TA)7 genotype was linked to specific colonic features or increased risk of precancerous lesions. Researchers collected data from 292 patients, analyzing their UGT1A1 genotypes and detailed information about their colorectal health.

The study revealed intriguing findings. While the UGT1A128 variant wasn't directly associated with specific colorectal cancer characteristics, there was a notable difference in aspirin usage. Patients with the (TA)7/(TA)7 genotype were significantly more likely to be taking aspirin. The results prompts us to consider:

Enzyme Activity: Does the UGT1A128 variant's impact on enzyme activity affect how the body processes potential carcinogens in the colon?
Tumor Location: Could the UGT1A1 genotype influence where tumors develop in the colon?
NSAIDs and CRC: How might NSAIDs interact with UGT1A1 variants to influence colorectal cancer risk?

The UGT1A128 variant doesn't appear to dictate specific colorectal cancer characteristics on its own. However, the link with aspirin use suggests a more complex interplay. Because individuals with the UGT1A128 variant and take aspirin for its protective effects. Further research may be necessary to fully determine the effect of aspirin on those with UGT1A128.

Personalizing Colorectal Cancer Strategies: The Future of UGT1A1 Research

While this study didn't establish a direct link between the UGT1A128 variant and colorectal cancer characteristics, it underscores the complexity of genetic influences on the disease. The unexpected finding regarding aspirin use highlights the potential for gene-environment interactions to play a significant role.

Future research should delve deeper into how UGT1A1 variants interact with other genetic and lifestyle factors to influence CRC risk. Exploring the enzyme's activity in relation to different carcinogens and medications could provide valuable insights for personalized prevention and treatment strategies. Additionally, investigating the potential impact of UGT1A1 variants on the effectiveness of chemopreventive agents like aspirin warrants further attention.

As our understanding of UGT1A1 and its role in colorectal cancer evolves, we may move closer to tailoring screening and prevention efforts based on individual genetic profiles. By considering the unique genetic makeup of each person, we can optimize strategies for early detection, personalized treatment, and ultimately, improved outcomes in the fight against colorectal cancer.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1016/j.dld.2018.11.032, Alternate LINK

Title: A Study Of The Association Between Ugt1A1*28 Variant Allele Of Ugt1A1 Gene And Colonic Phenotype Of Sporadic Colorectal Cancer

Subject: Gastroenterology

Journal: Digestive and Liver Disease

Publisher: Elsevier BV

Authors: Benjamin Anon, Clémence Perray, David Regnault, Morgane Caulet, Isabelle Orain, Bruno Godart, Jean-Christophe Pages, Anne Tallet, Mehdi Ouaissi, Serge Guyetant, Chantal Barin-Le Guellec, Thierry Lecomte

Published: 2019-04-01

Everything You Need To Know

How does the UGT1A1 gene influence the risk of developing colorectal cancer?

The UGT1A1 gene is responsible for producing an enzyme that helps the body detoxify harmful substances. Variations, like the UGT1A1*28 polymorphism, affect how efficiently this enzyme works, potentially influencing an individual's risk of developing colorectal cancer. This is because the enzyme's activity impacts how potential carcinogens are processed in the colon. While the precise mechanisms are still under investigation, understanding these genetic variations is crucial for refining screening strategies and personalizing treatment approaches.

What did the study discover about the relationship between the UGT1A1*28 variant and aspirin use in colorectal cancer patients?

The study revealed that patients with the (TA)7/(TA)7 genotype of the UGT1A1*28 variant were more likely to be taking aspirin. Although the UGT1A1*28 variant alone didn't directly influence colorectal cancer characteristics, this finding indicates a complex interaction between the variant and aspirin use, possibly for its protective effects. The exact nature of this interplay is still being researched, highlighting the potential for gene-environment interactions to influence colorectal cancer risk.

In what ways does the UGT1A1*28 variant impact enzyme activity and the detoxification of carcinogens in the colon?

The UGT1A1*28 variant influences enzyme activity, which in turn affects how potential carcinogens in the colon are processed. If the enzyme's activity is reduced due to the variant, it could lead to a less efficient detoxification process, potentially increasing the risk of colorectal cancer. The connection between NSAIDs (like aspirin) and UGT1A1 variants adds another layer of complexity. Further research is needed to fully understand these interactions.

Does the UGT1A1*28 variant affect specific characteristics of colorectal cancer, like tumor location or stage?

Currently, research has not definitively linked the UGT1A1*28 variant to specific colorectal cancer characteristics, such as tumor location or stage. However, the influence of the UGT1A1 genotype on where tumors develop in the colon remains a topic of interest. More studies are needed to explore whether the UGT1A1 genotype influences the development and progression of colorectal cancer, particularly in combination with environmental factors like diet and medication use.

Are there any other health implications or associations of the UGT1A1*28 variant beyond colorectal cancer, such as its impact on medication response?

While the UGT1A1*28 variant has been studied in relation to colorectal cancer, it's also known to affect how the body processes certain medications, like irinotecan, a chemotherapy drug. Individuals with the UGT1A1*28 variant may experience increased toxicity from these medications due to slower drug metabolism. Further research is needed to understand how the UGT1A1*28 variant may be associated with the effectiveness of cancer treatments and other potential health implications.