Certain body types may have a higher risk of developing colorectal cancer.
- 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.
Comparing 4
body phenotypes
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.
Same BMI,
different body shapes
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.
Different
gene enrichments in different body types
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.
Taller
height, more cancer cells?
“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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