Greater body fat leads to increased risk for cancers of the digestive system, a new study suggests.
Researchers found that fat mass is the main obesity-related risk factor for the cancers, and obesity influences certain cancer types but not others.
Researchers took genetic variants that influence an individual’s height and weight, and compared whether having genes that predispose an individual to increased body mass index (BMI) also predisposed them to higher risk of various cancer types.
They did the same for genes that predispose someone to being taller.
Increased genetic predisposition to being tall was consistently associated with increased risk across the different cancer types investigated.
While genetic predisposition to increased BMI was associated with increased risk of cancers of the digestive system.
This included cancer of the liver, stomach, oesophagus, and pancreas – but not associated with increased overall risk of other cancers.
Dr Stephen Burgess, a statistician based at the Medical Research Council Biostatistics Unit, part of the University of Cambridge, said: “It’s well known that being large is linked with having a greater risk of cancer.
“But what was not known is whether the increased risk is an inevitable result of being a big person, or whether it is caused by a specific component of obesity that people can change.”
Dr Amy Mason, a statistician at the Department of Public Health and Primary Care in the University of Cambridge, said: “The key message to the public should focus less on physical size, which people can often do little about, and more on managing the amount of fat that they carry.”
The study, conducted by researchers at the University of Cambridge, Imperial College London, Karolinska Institutet in Stockholm, and the University of Bristol, also found there were opposite directions of effect for different cancer types.
In particular for sex-linked cancers, genetic predisposition to increased BMI was associated with increased risk of cervical and endometrial cancer, but decreased risk of breast and prostate cancer.
Scientists also compared associations of genes that influence an individual’s fat mass versus fat-free mass to differentiate between these components of body size.
Fat mass is the portion of someone’s weight attributable to fat, and fat-free mass is an individual’s weight excluding body fat.
The increased risk of various digestive cancers was primarily attributable to fat mass, the research suggests.
Although the study did not provide any definitive evidence about the mechanisms, researchers say it is generally thought tall people have higher cancer risk because they have more cells in their body, so there are more chances for cancer to develop.
The researchers suggest a specific link between fat mass and digestive cancers may be driven by increased consumption of cancer-causing substances (carcinogens) in fatty food, or increased levels of fatty tissue leading to increased inflammation in the digestive tract.
Links between obesity and sex-specific cancers are likely driven by the production of reproductive hormones in fatty tissue.
Lead author, Dr Mathew Vithayathil, a clinical researcher in gastroenterology at Imperial College London, said: “This result has important clinical implications.
“While our research supports a causal role of obesity in driving and protecting against certain cancers, it suggests differential effects of BMI for different malignancies which should be explored further.
“Rather than presenting obesity as a generic cancer risk factor, a more nuanced public health message with regards to obesity as a risk factor for digestive system cancers may be more appropriate.”
The research, published in the journal PLOS Medicine, was based on data from 367,561 individuals from the UK Biobank study.
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