Patients who carry genetic variants linked to obesity face a significantly higher risk of death after surviving breast cancer, according to a large new study published in JAMA Network Open, underscoring the growing importance of personalized lifestyle interventions in cancer survivorship care.
The study analyzed data from 4,177 breast cancer survivors and found that women with the highest polygenic score (PGS) for body mass index (BMI) had a 15% higher risk of all-cause mortality compared with those in the lowest genetic risk group. Polygenic scores aggregate the effects of hundreds of genetic variants to estimate an individual’s inherited susceptibility to specific traits, including obesity.
Researchers noted that BMI-related polygenic scores are already known to be associated with cardiometabolic conditions, and the new findings suggest they may also serve as a valuable tool in guiding post-cancer care. According to the study team, genetic risk information could help clinicians tailor lifestyle recommendations aimed at improving long-term survival among breast cancer patients.
“Obesity is not only determined by genetics, so there are ways to mitigate the genetic contribution to mortality risk by adding additional steps,” said lead author Clara Bodelon, PhD, MS, of the American Cancer Society’s Department of Population Science in Atlanta. She emphasized that lifestyle changes could offset inherited risk.
Advances in large-scale genome-wide association studies (GWAS) have significantly improved understanding of obesity’s genetic underpinnings, with heritability estimates now ranging from 40% to 70%. At the same time, obesity rates continue to rise in the United States, compounding health risks for the growing population of cancer survivors. More than four million women in the U.S. are currently living after a breast cancer diagnosis, a figure expected to climb due to aging demographics and improvements in detection and treatment.
The research drew on data from the Cancer Prevention Study–II Nutrition Cohort, which has followed participants since the early 1990s. The analysis focused on postmenopausal women of genetically determined European ancestry who were diagnosed with a first primary nonmetastatic breast cancer between 1992 and 2017. Mortality data through 2020 were obtained via the National Death Index, and statistical models were used to assess the relationship between BMI-PGS and death risk.
Notably, the study found that lifestyle changes could meaningfully reduce genetic risk. Breast cancer survivors in the highest BMI-PGS group needed to walk about 1.7 additional hours per week—roughly 15 extra minutes per day—to reach a mortality risk comparable to those in the lowest genetic risk group.
While the analysis focused on older women, researchers highlighted the concerning rise in breast cancer diagnoses among women under 50 over the past two decades. Bodelon said future studies should examine whether similar genetic and lifestyle interactions are present in younger patients and explore whether other behaviors can further reduce inherited risk.
The research team also plans to investigate whether a genetic predisposition to obesity is linked to other long-term outcomes among breast cancer survivors, including the risk of developing second cancers, potentially broadening the role of genetic risk scores in survivorship planning.
