ACS Research Highlights

Genes Strengthen the Protective Effects of Fruit and Fiber

With data from ACS CPS-II and 44 other studies, scientists found genetic markers that interact with dietary fiber and fruit to reduce colorectal cancer risk.

The Challenge

Diets high in whole grains, fruits, vegetables, and dietary fiber have been linked with lowering the risk of developing colorectal cancer. But how they work is not fully known. 

Scientists think genetic variants/markers in people are likely the factor that modifies the way specific foods contribute to cancer prevention. The most common type of variants in the human genome are single nucleotide polymorphisms (SNPs). SNPs serve as genetic markers to help scientists locate the specific genes associated with a specific disease.

Researchers are still at the early stages of exploring gene-diet interactions, which are a specific type of gene-environment (GxE) study. Until recently, only one significant interaction had been found—between eating processed meat and the SNP rs4143094 near the gene GATA3.

One of the main limiting factors for discovering other gene-diet interactions has been small numbers of participants in the study. 

Putting It All Together 

Each chromosome contains 100s or 1,000s of individual genes. A genetic marker is a gene sequence at a known, distinctive location on a chromosome. That location is called the locus. A SNP (single nucleotide polymorphism) is a variation in DNA sequence and is also called a single locus marker. A GWAS (genome-wide association study) rapidly scans many people’s DNA to find small genetic variations/SNPs. These SNPs may contribute to certain diseases, like cancer. Some GWAS look at gene-environment (GxE) interactions( for instance, a gene interacting with a drug or food) to see if SNPs strengthen or weaken the way something in the body’s environment works.

See the Glossary for Nonscientists for definitions of the bold terms, and more.

The Research

A recent study in eBiomedicine, (part of The Lancet Discovery Science) aimed to clarify whether eating fruits, vegetables, or foods rich in dietary fiber influence the risk of developing colorectal cancer and also to identify the specific genetic markers/SNPs involved.

In this largest genome-wide study involving nearly 70,000 participants, our research group identified two genetic loci that influence how dietary fiber and fruit intake affect colorectal cancer risk. Our findings suggest that higher dietary fiber and fruit intake reduce the risk of developing colorectal cancer, enhancing our understanding of the interplay between diet and genetics in colorectal cancer development. Further research is needed to validate these results and explore the underlying mechanisms."

Anita Peoples, PhD, MPH

Senior Principal Scientist, Cancer Survivorship and Epidemiology Research

Population Science, American Cancer Society

Compared to people without cancer (the control group), the group with colorectal cancer (the case group) tended to:

  • Be older.
  • Have a higher body mass index (BMI) and consume more calories.
  • Be more likely to have a family history of colorectal cancer.
  • Have a higher prevalence of type 2 diabetes.
  • Be more likely to have a history of smoking tobacco.
  • Eat less dietary fiber, fruit, and vegetables.

Discovery of a SNP that Strengthens the Protective Effects of Fiber

One of the two significant interaction SNPs the researchers found in this G x fiber interaction with colorectal cancer was rs4730274 (close to the SLC26A3 gene).

This SNP showed the most significant interaction effect. It's been linked with:

  • Inflammatory bowel disease (IBD). Current evidence suggests that people with IBD in remission who eat dietary fiber are more likely to stay in remission compared with those who don’t eat it. It’s also well documented that people with IBD have a higher risk for developing colorectal cancer. 
  • Ulcerative colitis (UC). People with UC in remission who eat a high-fiber diet have decreased signs of inflammation. Chronic inflammation increases the risk of colorectal cancer.
Based on this information, the study authors say, "it seems feasible" that the protective effect of fiber is stronger in people who are genetically prone to these inflammatory intestinal disorders.
 
Dietary fiber promotes the growth diversity of bacterial populations in the gut, which in turn, increases the expression of SLC26A3. The gut also metabolizes fiber into short-chain fatty acids, which have been shown to have anti-inflammatory and anti-carcinogenic effects.
 

Based on their own test results and current knowledge about how fiber operates in the body, the authors concluded that SLC26A3, the gene near the rs4730274 SNP, “probably functions as a tumor suppressor." 

 

Discovery of an SNP that Strengthens the Beneficial Effects of Eating Fruit 

The second significant interaction SNP identified by the researchers was found to interact with fruit: rs1620977 in the NEGR1 gene.

The NEGR1 gene is linked with the regulation of body weight. The researchers suggest that this gene, similar to SLC26A3, may also play a role in tumor suppression.

 

How the Study Was Done

The researchers analyzed a large-scale dataset of 69,734 participants (with European ancestry) from 45 studies from 3 genetic consortia that focus on genetics and colorectal cancer. (Consortia are a group of scientists from multiple institutions who collaborate on projects and pool resources.)

This study pool included data from the American Cancer Society Cancer Prevention Study-II.
 
The diet information came from food-frequency questionnaires and diet histories provided by the study participants.
 
The research team conducted several tests and analyses to detect interactions between specific genes and dietary fiber, fruits, or vegetables. These included:
 
  • A genome-wide interaction scan (GWAS) to look for recurring SNPs that might be associated with the prevention of colorectal cancer.
  • A gene-environment (GxE) analysis (a specific type of GWAS) to see if the SNP was modified by any 1 of the 3 food types being studied to increase the preventative factor for colorectal cancer. This study was the largest GxE study to date.
  • A more advanced and powerful test called a 3-DF joint test, which increases the ability to detect interacting disease susceptibility loci—specific points/locations on the gene—which helps with further evaluations.

Several American Cancer Society (ACS) researchers participated in this study: Christina Newton, MSPH; Anita Peoples, PhD, MPH, and Caroline Um, PhD, MPH, RD. Data from the ACS Cancer Prevention Study-II was part of the data pool. Andrew T. Chan, MD, MPH, with Massachusetts General Hospital in Boston and an ACS Professor was also one of the study's authors.

Why It Matters

The results of this study add to the existing evidence that genetic markers/SNPs can identify genes that are associated with the risk of developing colorectal cancer.

Specifically, they found supportive evidence that the SNP rs4730274 and the gene close to it, SLC26A3, have interactions with fiber consumption, chronic inflammatory disorders, and overall gut function that modify the strength of fiber's protective effect related to the risk of developing colorectal cancer.

They also found a second significant interaction SNP (rs1620977 in the NEGR1 gene) that modified the strength of fruit’s protective effect for the development of colorectal cancer.

This analysis was limited to individuals of European ancestry and captured food intake at only one point in time, so future studies will need to replicate these findings in people with European ancestry as well as demonstrate them with other ethnicities and races.