Patients with genes that increase risk of obesity are also at higher risk of death after breast cancer, a new study in JAMA Network shows.
This study of 4,177 breast cancer survivors found that those with a polygenic score (PGS) for body mass index (BMI) in the top range had a 15% higher mortality risk compared with those with the lowest score.
PGSs have been found to be associated with increased risk of cardiometabolic traits as well as obesity, among other conditions. According to this team’s findings, PGS scores could be used to recommend personalized lifestyle recommendations that could improve breast cancer patients’ long-term survival.
“Obesity is not only determined by genetics, so there are ways to mitigate the genetic contribution to mortality risk by adding additional steps,” lead author Clara Bodelon, PhD, MS, told Inside Precision Medicine. She is from the department of population science at the American Cancer Society in Atlanta.
Recent large genome-wide association studies (GWAS) have increased understanding of the genetic contribution to BMI. Estimates of the heritability of obesity now range between 40% and 70%.
More than four million women in the U.S. are now living after a breast cancer diagnosis, and this number is expected to increase due the underlying aging of the population and improvements in diagnosis, treatment, and supportive care. Meanwhile, the rate of obesity is increasing in the U.S. Obesity is defined as having a BMI, calculated as weight in kilograms divided by height in meters squared, of 30 or greater.
This team’s cohort research is part of the Cancer Prevention Study–II Nutrition Cohort, a large study in which participants responded to a survey in 1992 and to biennial follow-up surveys starting in 1997. The cohort includes women from 21 U.S. states diagnosed with a first primary nonmetastatic breast cancer between 1992 and 2017 with genetic data.
Analyses were restricted to postmenopausal women at the time of cancer diagnosis who had genetically determined European ancestry. Data analysis was conducted from July 2023 to July 2025. They used a polygenic score for body mass index (BMI-PGS), computed using summary statistics from 941 single nucleotide variants reported in a meta-analysis of genome-wide association studies that included approximately 700,000 individuals.
Deaths through 2020 were tracked via linkage with the National Death Index and Cox proportional hazards regression models were used to calculate hazard ratios for the association between BMI-PGS and all-cause mortality.
But, breast cancer survivors with a BMI-PGS in the highest tertile needed to walk approximately 1.7 hours per week more to be at a similar risk level as BC survivors in the lowest tertile, which corresponds to approximately an extra 15 minutes of walking each day of the week.
This study was conducted among older women, but one of the worrying recent trends has been the steady increase of diagnoses of breast cancer in women under age 50 over the past two decades, with steeper increases in more recent years.
Bodelon said, “New studies should be done in younger women to see if we observe the same associations. We would also like to see if other lifestyle factors can also mitigate the genetic risk.”
Meanwhile, Bodelon and her collaborators “want to look at whether being genetically predisposed to higher obesity is associated with other outcomes among breast cancer survivors, such as second cancers.”
