Genetic predisposition to higher BMI ups mortality risk in breast cancer survivors

Nonmetastatic breast cancer survivors who are genetically predisposed to having an excess body weight appear to be at increased risk of mortality, as shown in a study.

The study included 4,177 women diagnosed with a first primary nonmetastatic BC (median age at diagnosis 71.5 years) and had available genetic data from the Cancer Prevention Study–II Nutrition Cohort.

Researchers calculated a polygenic score for body mass index (BMI-PGS) using summary statistics from 941 single nucleotide variants reported in a meta-analysis of genome-wide association studies that involved around 700,000 individuals.

Women with a BMI-PGS in the top (high-risk group) vs lowest tertile (control group) were more likely to have a BMI of ≥30 kg/m² (24.8 percent vs 12.4 percent). A total of 2,114 women (50.6 percent) died over a median follow-up of 14.5 years.

Cox proportional hazards regression models showed that women in the high-risk group had a 15-percent increased risk of all-cause mortality compared with those in the control group (hazard ratio [HR], 1.15, 95 percent confidence interval [CI], 1.04–1.28).

Of note, women in the high-risk group had to do an extra 15 min of walking each day of the week to offset their genetic disadvantage and have their mortality risk drop to match that of the women in the control group.

The findings underscore the need for targeted lifestyle recommendations to mitigate the genetic predisposition for excess body weight in breast cancer survivors and lower the associated mortality risk.