Kajsa Sjöholm and Magdalena Taube, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg.
Photo Credit: Göteborgs Universitet, Emelie Taube
Scientific Frontline: Extended "At a Glance" Summary: Bariatric Surgery and Cancer Risk Reduction
The Core Concept: Substantial, sustained weight loss achieved through bariatric surgery significantly lowers the risk of developing and dying from cancer, particularly female-specific cancers like breast and gynecological cancers.
Key Distinction/Mechanism: The reduction in cancer risk is not uniform; it is heavily influenced by biological interactions rather than weight loss alone. Risk reduction is most pronounced in women exhibiting high baseline insulin levels and carrying specific genetic variants, highlighting a complex metabolic and genetic mechanism.
Origin/History: These clinical insights stem from the Swedish Obese Subjects (SOS) study, a long-term, globally unique prospective investigation led by the University of Gothenburg, with pivotal mechanism-focused findings published in PLOS Medicine and Scientific Reports in early 2026.
Major Frameworks/Components:
- Metabolic Indicators (Insulin): Elevated insulin levels prior to surgery serve as a critical marker for those who will experience the most significant cancer risk reduction post-surgery.
- Genetic Predisposition (FTO Gene): The FTO genetic variant (rs9939609), typically associated with high BMI and breast cancer, dictates surgical benefit. Women carrying this variant saw a 47% lower breast cancer risk, which increased to 64% if they also had high insulin levels.
- Gender-Specific Outcomes: The protective effects of bariatric surgery against cancer incidence and mortality were documented exclusively in women, with no corresponding risk reduction observed in male patients.
Branch of Science: Metabolic Medicine, Oncology, Endocrinology, and Clinical Genetics.
Future Application: These discoveries lay the foundation for precision medicine in obesity and oncology. Future weight-loss interventions—including advanced anti-obesity pharmaceuticals—can be precisely targeted based on a patient’s gender, metabolic baseline, and genetic profile to maximize cancer prevention.
Why It Matters: As obesity remains a leading driver of global cancer rates, understanding the precise biological pathways between weight loss and cancer prevention enables physicians to optimize treatments and save lives through highly personalized preventative care.
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 as 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 (SOS) study, which 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 globally, 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 cancers, and most evident in women who had high insulin levels even before surgery. The results indicate that insulin may be a key factor in the connection among 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.
The findings showed that women who carried a common genetic variant in the FTO gene—a gene previously linked to both high BMI and increased breast cancer risk—exhibited 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 observed.
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 as new, highly effective drugs for weight loss rapidly change 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," says Magdalena Taube, associate professor at the University of Gothenburg and a lead researcher for the current studies.
Published in journal:
- PLOS Medicine
- Scientific Reports
Title:
- Sex-specific associations between surgery-induced weight loss and cancer outcomes: A post hoc analysis of the prospective, controlled Swedish Obese Subjects study
- Association between FTO rs9939609 genotype and breast cancer risk after bariatric surgery in the Swedish Obese Subjects study
Authors:
- Kajsa Sjöholm, Per-Arne Svensson, Johanna C. Andersson-Assarsson, Peter Jacobson, Sofie Ahlin, Cecilia Karlsson, Björn Carlsson, Felipe M. Kristensson, Per Karlsson, Markku Peltonen, Lena M. S. Carlsson, and Magdalena Taube
- Elin Langegård, Felipe M. Kristensson, Johanna C. Andersson-Assarsson, Markku Peltonen, Per-Arne Svensson, Peter Jacobson, Sofie Ahlin, Kajsa Sjöholm, Lena M. S. Carlsson & Magdalena Taube
Source/Credit: Göteborgs Universitet
Edited by: Scientific Frontline
Reference Number: med052526_01