Scientists uncover a genetic 'shield' that lowers the risk of colorectal cancer

by Wayne State University

edited by Lisa Lock, reviewed by Andrew Zinin

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A team of scientists from the Barbara Ann Karmanos Cancer Institute, Wayne State University and institutions across the U.S. have published a new paper on the role of TGFBR1*6A, a naturally occurring genetic mutation in the TGFBR1 gene found in approximately 14% of the general population.

The study, "TGFBR1*6A and risk for colorectal cancer," published June 9, 2026, in Cancer Communications, focuses on TGFBR1*6A and how it influences a person's risk of developing colorectal cancer. Dr. Boris Pasche, president and CEO of the Karmanos Cancer Institute and chair of the Wayne State University Department of Oncology, was the first to discover TGFBR1*6A as a cancer risk allele.

"This mutation has often been overlooked by genome-wide association study chips, which cannot detect TGFBR1*6A, and is commonly missed by next-generation sequencing platforms due to the complexity of the region," said Dr. Allan Johansen, a postdoctoral fellow and first author of the paper.

"In this study, we demonstrated that carriers of TGFBR1*6A have a reduced risk of developing colorectal cancer. This protective effect is even more pronounced in siblings of patients and in patients with familial adenomatous polyposis—a rare, inherited genetic condition that causes hundreds or more precancerous growths—called polyps—to form inside the colon and rectum. If left untreated, these polyps will inevitably turn into colorectal cancer, typically by around age 40."

For a long time, standard genetic sequencing tools overlooked this variant because of the difficulty of reading it with DNA sequencing methods. To understand its role, the researchers engineered a special "humanized" mouse model carrying this genetic code and examined extensive genetic data from a global registry of human families. They discovered that having this specific genetic variation acts like a natural shield, noticeably reducing the risk of colorectal cancer. Their findings could have significant implications for personalized patient care in the future.

Pasche shared the history and importance of the findings from this research.

"The journey began with the identification of TGFBR1*6A during my postdoc in Joan Massagué's lab in the late 1990s," said Pasche. "Functional assessments showed that TGFBR1*6A transduced TGF-beta signals less effectively than its wild-type counterpart, TGFBR1. Early studies suggested that TGFBR1*6A may act as a colorectal cancer susceptibility allele; however, subsequent research by other groups did not confirm this association.

"Together with my longtime collaborator, Dr. Antonio Di Cristofano, we developed a mouse model of TGFBR1*6A by replacing the murine Tgfbr1 exon 1 with the human TGFBR1*6A or TGFBR1 exon 1. This model revealed that mice carrying the TGFBR1*6A allele developed fewer polyps and adenocarcinomas compared with those with two copies of the TGFBR1 allele."

In collaboration with the Colon Cancer Family Registry, the research team led by Pasche assessed the association of TGFBR1*6A with colorectal cancer risk among patients and their unaffected siblings. The findings were strikingly similar in humans, establishing TGFBR1*6A as a colorectal cancer protective allele. These results are the culmination of years of work and support from the NCI, AACR and ACS.

More information

Allan M. Johansen et al, TGFBR1 *6A and Risk for Colorectal Cancer, Cancer Communications (2026). DOI: 10.34133/cancomm.0033

Key medical concepts

Colorectal CancerFamilial adenomatous polyposisTransforming Growth Factor beta

Clinical categories

OncologyClinical geneticsGastroenterology Provided by Wayne State University Who's behind this story?

Lisa Lock

BA art history, MA material culture. Former museum editor, paramedic, and transplant coordinator. Editing for Science X since 2021. Full profile →

Andrew Zinin

Master's in physics with research experience. Long-time science news enthusiast. Plays key role in Science X's editorial success. Full profile →

Citation: Scientists uncover a genetic 'shield' that lowers the risk of colorectal cancer (2026, June 23) retrieved 23 June 2026 from https://medicalxpress.com/news/2026-06-scientists-uncover-genetic-shield-lowers.html This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.