Substantial and sustained weight-loss has been linked to a reduced risk of cancer and cancer-related death, mainly in women. Two new studies now provide clues to why the risk is reduced - and suggest that gender, metabolism and genetics may play a crucial role.
The studies are based on the long-term Swedish Obese Subjects study (SOS Study) that investigates the effects of weight-loss surgery. More than 4,000 individuals with obesity are included, half of whom underwent bariatric surgery. The SOS study, which is unique in the world, is led and coordinated by the University of Gothenburg.
In one of the current studies, published in PLOS Medicine, all participants in the SOS study were analyzed with a focus on gender differences, insulin levels and long-term cancer outcomes. The researchers found that weight-loss following surgery was linked to both lower cancer risk and cancer-related mortality in women, but not in men.
The link was particularly clear for female-specific cancers, such as breast and gynecological cancer, and most evident in women who had high insulin levels even before the surgery. The results indicate that insulin may be a key factor in the connection between obesity, weight loss and cancer.
The role of genetic background
In a complementary study in Scientific Reports, the researchers went a step further and investigated whether genetic background can influence the reduction in breast cancer risk following weight loss induced by bariatric surgery. The study included women with obesity who were followed for up to 33 years.
Here, it was found that women who carried a common genetic variant in the FTO genetic variant - a gene previously linked to both high BMI and increased breast cancer risk - showed the strongest association between surgery and lower breast cancer risk. In these women, the risk of breast cancer was approximately 47 percent lower after bariatric surgery compared with standard obesity treatment. In women who lacked the gene variant, no clear risk reduction was seen.
The association was even stronger in women who both carried the FTO genotype and had high insulin levels at the start of the study; in this group, the risk of breast cancer was approximately 64 percent lower after bariatric surgery. The results suggest that genetic background may affect how the body responds to extensive and long-term weight loss in terms of cancer risk.
Together, the studies indicate that the reduced risk of cancer after weight loss is unlikely to be due to a single factor. Instead, the results suggest that several biological mechanisms may interact, with factors such as insulin, gender and genetic background likely playing an important role.
Strategies for cancer prevention
"Our results suggest that there are biological differences between individuals that affect how much cancer risk is reduced after weight loss. By understanding these differences, we will get closer to the mechanisms underlying the connection between obesity and cancer", says Kajsa Sjöholm, associate professor at the University of Gothenburg.
The findings are particularly relevant in a situation where new, highly effective drugs for weight loss are rapidly changing the treatment of obesity. Knowledge of the mechanisms behind reduced cancer risk may in the long term contribute to more accurate strategies for cancer prevention.
In the longer term, this may pave the way for a more precision medicine approach, where preventive interventions are adapted to, for example, gender, metabolic health and genetic background."
Magdalena Taube, Associate Professor at the University of Gothenburg
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