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Could Genetics Influence Cancer Risk From Red and Processed Meats?

A person holding two packages of red meat in a supermarket.
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Researchers have explored whether genetics can influence the risk of colorectal cancer from the consumption of red and processed meat, identifying two genetic markers that may put some people at increased risk.

The study is published in Cancer Epidemiology, Biomarkers & Prevention.

How do red and processed meats influence cancer development?

Studies have generated strong evidence for the link between the consumption of red and processed meat and negative health outcomes – particularly the risk of developing colorectal cancer.

Despite evidence for the strength of this association, researchers haven’t yet worked out why this is the case, and establishing the mechanisms underpinning this effect could be key to prevention.

In the new study, researchers from the University of Southern California (USC) Norris Comprehensive Cancer Center at the Keck School of Medicine investigated if differences in our genes could influence the risk of cancer from red and processed meat consumption. This research forms one of the largest gene–environment studies of the association between red meat and colorectal cancer.

Uncovering clues with genomic analysis

The researchers analyzed data from almost 30,000 people with colorectal cancer and nearly 40,000 without cancer, taken from 27 studies of colorectal cancer risk in people of European origin.

The researchers first created standard measures for the consumption of red and processed meat and divided participants into four groups based on their level of consumption, as well as calculated daily servings and adjusted for body mass index.

The analysis of these groups revealed that those who consumed the most red meat (such as beef, pork and lamb) had a 30% increased risk of colorectal cancer, while those who consumed the most processed meat (such as bacon, sausages, deli meats and hot dogs) had a 40% increased risk. However, these do not account for genetic variability that may alter an individual's risk.

Next, the research team used DNA samples to conduct a genome-wide search for positions in the genome known as single nucleotide polymorphisms (SNPs) that may alter cancer risk in those who ate more red meat.

They compiled data for over 7 million of these variants, revealing two SNPs that influenced cancer risk levels based on red or processed meat consumption. The first was located near the HAS2 gene, which has a known link to colorectal cancer but not to red meat consumption.

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People who possess a common variant of the HAS2 gene (found in 66% of the population) faced a 38% higher risk of colorectal cancer if they consumed the largest amount of red meat. However, people with another rarer variant had no such increased risk.

The second SNP identified was part of the SMAD7 gene that regulates hepcidin, a protein linked to iron metabolism. Variants in this gene may affect the way the body processes iron, which the researchers suggest could increase cancer risk with high consumption of iron-rich red and processed meats.

“When hepcidin is dysregulated, that can lead to increased iron absorption and even iron overload inside cells,” said the study’s lead author Mariana C. Stern, a professor of population and public health sciences and urology at the USC Norris Comprehensive Cancer Center.

People who ate high levels of red meat and had two copies of a SMAD7 variant that is present in nearly three-quarters of the population faced an 18% greater risk of colorectal cancer. Meanwhile, those with only one copy of this variant or two copies of a less common variant had even higher risks – 35% and 46%, respectively.

“These findings suggest that different genetic variants may confer a differing risk of colorectal cancer in individuals who consume red meat, and highlight possible explanations for how the disease develops,” explained Joel Sanchez Mendez, study co-author and doctoral student in the Keck School of Medicine.

Searching for a causal link

However, the study’s findings do not yet prove a causal link for these genetic variants.

“These findings suggest that there’s a subset of the population that faces an even higher risk of colorectal cancer if they eat red or processed meat,” Stern explained. “It also allows us to get a peek at the potential mechanism behind that risk, which we can then follow up with experimental studies.”

“This gives us some important food for thought,” Stern added. “We do these gene–environment interaction studies when we know there’s a clear association between an environmental exposure and a disease, but what happens in between is still a black box.”

Stern and colleagues now aim to follow up with additional experimental studies to probe the potential role of dysregulated iron metabolism in colorectal cancer development.

Reference: Stern MC, Sanchez Mendez J, Kim AE, et al. Genome-wide gene–environment interaction analyses to understand the relationship between red meat and processed meat intake and colorectal cancer risk. CEBP. 2024;33(3):400-410. doi: 10.1158/1055-9965.EPI-23-0717

This article is a rework of a press release issued by Keck School of Medicine of USC. Material has been edited for length and content.