Obesity as a risk factor for colorectal cancer underestimated so far
Weight loss before diagnosis masks the association
obesity is a known risk factor for colorectal cancer. Scientists at the German cancer Research Center (DKFZ) have now demonstrated, using data from nearly half a million participants in the UK Biobank cohort, that this association has probably been significantly underestimated to date. The reason: Many affected individuals unintentionally lose weight in the years before a colorectal cancer diagnosis. If studies only consider body weight at the time of diagnosis, this masks the actual association between obesity and colorectal cancer risk.
Obesity is a risk factor for a whole range of cancers. This association is particularly clear, for example, in the case of uterine cancer, kidney cancer and also colorectal cancer. According to previous estimates, obese* people have up to a third higher risk of colorectal cancer than people of normal weight.
"However, these studies have so far not taken into account the fact that many affected people lose weight in the years before their colorectal cancer diagnosis," says Hermann Brenner, epidemiologist and prevention expert at the German Cancer Research Center. "This has led to a significant underestimation of the risk contribution of obesity, as we recently demonstrated with a first study."
To validate this finding on a larger cohort, the researchers led by Brenner were now able to access data from the UK Biobank. This prospective cohort study on lifestyle and health includes about half a million participants from all over the UK who were recruited between 2006 and 2010 at the age of 40 to 69 and have been followed up since then.
During a median follow-up period of ten years, 4,794 of the total 453,049 participants developed colorectal cancer. To avoid possible bias due to prediagnostic weight loss when calculating the association between obesity and colorectal cancer risk, the researchers excluded the first years of the follow-up period. This actually made the association much clearer. The explanation: a relevant proportion of cancers diagnosed in the first years of follow-up were apparently already present at study entry, without causing symptoms, and may have led to weight loss.
When the calculation took into account the entire up to 13 years of follow-up, the risk of colorectal cancer was 13 percent (women) and 23 percent (men) higher for overweight persons than for normal-weight persons. However, if cancer diagnoses during the first seven years of follow-up were excluded from the calculation, the risk for overweight individuals was increased by 26 percent (women) and 42 percent (men).
The Heidelberg epidemiologists also calculated the share of colorectal cancer cases in the study population statistically attributable to obesity ("population attributable fraction", PAF). If they took into account the entire up to thirteen years of follow-up, the PAF was 11.3 percent. In contrast, when the first seven years were excluded, 19 percent of colorectal cancer cases were attributable to overweight and obesity.
"This is a significant increase over previous estimates, which had assumed a risk ratio of 5 to 11 percent," says study leader Hermann Brenner. "Obesity is apparently responsible for a much larger proportion of colorectal cancer cases than previously thought. The high and still growing proportion of overweight people in large parts of the world is likely to continue to significantly increase colorectal cancer case rates in many countries in the coming years.
The causes of the prediagnostic weight loss are considered to be the increased metabolism caused by the tumor and systemic inflammation, both of which increase energy consumption. Experts estimate the duration of the prediagnostic phase at an average of three to six years.
The epidemiologist therefore recommends paying more attention to the time at which weight measurements are taken when planning future studies. "For the assessment of colorectal cancer risk, it is probably more decisive how many years of life a person carries around how much excess weight, rather than the current weight. On the other hand, unintentional weight loss in adulthood may also be an indication of undiagnosed cancer, and the cause should therefore be carefully investigated," Brenner said.
* Overweight from a body mass index of ≥30 kg/m2 is considered obesity
Original publication
Fatemeh Safizadeh, Marko Mandic, Dianne Pulte, Tobias Niedermaier, Michael Hoffmeister, Hermann Brenner; "The underestimated impact of excess body weight on colorectal cancer risk: Evidence from the UK Biobank cohort"; British Journal of Cancer, Volume 129, 2023-7-13
Marko Mandic, Fatemeh Safizadeh, Tobias Niedermaier, Michael Hoffmeister, Hermann Brenner; "Association of Overweight, Obesity, and Recent Weight Loss With Colorectal Cancer Risk"; JAMA Network Open, Volume 6, 2023-4-21
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