2 body types may be linked to higher colorectal cancer risk

By Staff 9 Min Read

  • Previous research has established a link between height and fat accumulation around the waist.
  • While research has already shown that people of European ancestry who are tall or who have obesity are more at risk of colorectal cancer, new research has indicated that this pattern exists across a number of ancestral groups.
  • Researchers propose that their analysis suggests that height is less associated with cancer risk than previously thought.

People who have obesity, or are tall with fat accumulation around their middle, are at an increased risk of colorectal cancer, regardless of their ancestry.

Repeated studies have made the link between obesity and height and increased cancer risk, including colorectal cancer. For example, a study published in 2022 showed that people of European ancestry who are tall and centrally obese, as well as people with general obesity, have a higher risk of developing colorectal cancer.

Now, an international team of researchers has analyzed health data reported for 329,828 U.K. Biobank participants of Caucasian, African, Asian, and/or Chinese ancestries and shown that this pattern exists across all of them.

For the study, published in Science Advances, researchers looked at the impact of height, obesity, and fat distribution on an individual’s risk of colorectal cancer.

They split participants in the cohort into four groups based on their body shape as defined by height and fat distribution. They used data that had been collected on body mass index (a calculation that is used to infer adiposity), height, weight, waist-to-hip ratio, and waist and hip circumference to determine which group an individual fits into.

The four groups were:

  • PC1 generally obese
  • PC2 tall, but with more distributed fat mass
  • PC3 tall, centrally obese
  • PC4 lower height, high weight, and BMI but lower hip and waist measurements.

They found that individuals in the PC1 group had a 10 percent higher risk of colorectal cancer in this cohort, and those in the PC3 group, had a 12 percent higher risk of colorectal cancer, which rose to 18 percent higher for women.

The other two groups had a small, but not significant increase in their risk of cancer.

Heinz Freisling, PhD, study author and scientist from the International Agency for Research on Cancer, Lyon, France in the Nutrition and Metabolism Branch said:

“We believe that the most used indicators of body fatness such as body mass index, or body fat distribution (e.g., waist circumference) are underestimating cancer risk due to unhealthy weight. Despite their usefulness, these indicators group individuals with similar body mass index, but with different body shape, into the same category, while we know that people with the same body mass index can have very different cancer risk.”

Their findings confirmed that fat accumulation around the middle of the body, or around the abdomen, was linked to a higher risk of colorectal cancer.

Further analysis of the cohort found that the increased risk of colorectal cancer in these body types was seen in people of Caucasian, African, Asian, and/or Chinese ancestries.

“There are probably only limited possibilities, which are common across ancestral groups, of how body measures such as weight and height can combine to form a body shape. It also suggests that biological processes determining body shape are evolutionary conserved as they are molecular pathways key for the individual’s survival,” Freisling said.

A genome-wide association study was then done using genomic data on 460,198 UK Biobank participants. Researchers identified 3,414 genetic variants associated with body shape. These were found to be differentially expressed in different tissues across the four different body categories created by the researchers.

Those with that genetic variants associated with a PC1 body shape had increased expression in the brain and pituitary gland tissues, and those associated with a PC3 body shape had increased genetic expression in the adipose tissue, breast, nerve, blood vessel tissues, and female reproductive organs.

“The results of our genetic analysis at the tissue level suggest several mechanisms, which likely reflect different adiposity subtypes. These are dysregulation of blood glucose levels and metabolism, i.e., processes that convert food into energy, but also increased inflammation and hormones produced in adipose tissue, known as adipokines. A well-described adipokine is leptin, which regulates appetite but is potentially directly relevant to cancer development. For example, leptin increases the rate of cell division,” Freisling explained.

“Strong evidence suggests that there is a general effect of height on cancer risk,” Leonard Nunney, professor of biology and an evolutionary biologist at the University of California, who was not involved in the research, told Medical News Today.

He has previously carried out analysis showing that the 10% increase in cancer risk seen per additional 4 inches in height in humans, is due to a higher number of cells in the bodies of taller people as they are larger.

The authors of the study propose in their discussion that the role of height in cancer risk has been overstated in previous research that did not consider waist-to-height ratio, and therefore, central adiposity.

Nunney said that calculating lean mass would have been helpful to test the cell number hypothesis, which is thought to underpin the link between height and increased cancer risk.

“In the present study, the authors used height (untransformed in any way) in defining their PCs, an approach that may underestimate the role of height in CRC since height squared (if we assume the BMI allometry) is the relevant variable for cancer risk,” he said.

Is height or higher fat a bigger risk for colorectal cancer?

Nunney also explained that he was not aware of any data into the relative size or amount of colorectal tissue people have, relating to their height, which makes it difficult to understand if these findings of increased risk of colorectal cancer are due to a higher number of cells, or due to increased adiposity, or both.

“It is certainly possible that the amount of tissue is affected not only by height but also by body shape,” he added.

“This publication is a useful step in understanding the relative importance of cell number vs adiposity (and maybe the type of adiposity) in the incidence of colorectal cancer. Height-squared is a very imperfect metric of lean body mass (which we assume is proportional to cell number), and research that allows us to add body shape in the estimate could help us understand this cell number effect more fully,” said Nunney.

Next, the team of researchers behind this latest paper wishes to identify genes underlying the relationship between body shapes and genetic expression to help explain the mechanisms underpinning their latest findings.

“We will be next trying to identify how these body shapes affect the composition of proteins in our body, which will help to better understand the link between body shapes and cancer development,” said Freisling.

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