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2019 NCRI: Use of Mendelian Randomization to Determine Role of Human Gut Microbiome in Colorectal Cancer Development


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A study using a technique called Mendelian randomization to investigate the causal role played by bacteria in the development of colorectal cancer was presented at the 2019 National Cancer Research Institute (NCRI) Cancer Conference.

Photo credit: Getty

First study author Kaitlin Wade, PhD, of the University of Bristol, said in a press release, “We found evidence that the presence of an unclassified type of bacteria from a bacterial group called Bacteroidales increased the risk of [colorectal] cancer by between 2% and 15%. This means that, on average, people with this type of bacteria within their gut may have a slightly higher risk of [colorectal] cancer compared to those who don’t. We were able to use Mendelian randomization to understand the causal role that these bacteria may have on the disease. Our findings support previous studies that have shown that Bacteroidales bacteria are more likely to be present, and in larger quantities, in individuals with [colorectal] cancer compared to those without the disease.”

Methods

Dr. Wade, who is an early-career researcher, said, “I was interested to see whether variation in the human gut microbiome, like the number of bacteria or simply the numbers of different types of bacteria, can have an impact on [colorectal] cancer [risk]. Lots of studies in mice and humans have shown an association between the gut microbiome and [colorectal] cancer, but very few have provided convincing evidence for causality. In other words, it’s really difficult to discern whether components of the gut microbiome can cause [colorectal] cancer, whether the disease itself leads to variation in the gut microbiome, or whether the association is due to some other factors that cause variation in both.”

“Our study confirmed observational evidence suggesting that genera within this bacterial order are more present in colorectal cancer cases than controls and provides further evidence that this may be due to a causal impact of these bacteria on colorectal cancer.”
— Wade et al

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Mendelian randomization uses complex statistical analysis of data from large populations to provide evidence for cause and effect rather than just the existence of an association.

“With Mendelian randomization, we use people’s natural, randomly inherited genetic variations, which alter levels of bacteria within the gut microbiome in a way that mimics a randomized trial, to see whether people with a different genetic makeup, and therefore different gut microbiome profiles, have a different risk of colorectal cancer,” explained Dr. Wade. “In this way, we don’t have to edit anyone’s gut microbiome directly by giving antibiotics or probiotics in a randomized trial or waste time waiting to see whether people within the population get colorectal cancer. We just need studies that have already got this information measured.”

The researchers used data from 3,890 people taking part in the Flemish Gut Flora Project, the German Food Chain Plus study, and the PopGen study, and 120,328 people in the international Genetics and Epidemiology of Colorectal Cancer Consortium. These studies searched for small variations in the genomes of participants that occur more frequently in people with a particular disease or characteristic than in people without that disease or characteristic, known as genome-wide association studies.

Findings

Of the 157 microbial traits assessed in the genome-wide association studies of the gut microbiome, there was evidence of host genetic contribution to 13. The analysis also found people with an unclassified type of bacteria from the Bacteroidales group had a higher risk of colorectal cancer compared to people who did not have these bacteria—8% higher (95% confidence interval = 2%–25%, P = .02).

The authors concluded, “Our study confirmed observational evidence suggesting that genera within this bacterial order are more present in colorectal cancer cases than controls and provides further evidence that this may be due to a causal impact of these bacteria on colorectal cancer.”

Disclosure: For full disclosures of the study authors, visit abstracts.ncri.org.uk.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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