Physical activities and breast cancer: a Mendelian randomization study

Area of Science:

• Genetics
• Epidemiology
• Oncology

Background:

• The relationship between physical activity (PA) and breast cancer (BC) is suggested but not definitively causal.
• Mendelian randomization (MR) offers a method to investigate causal links using genetic variants.

Purpose of the Study:

• To explore the potential causal relationship between physical activity and breast cancer using Mendelian randomization analysis.
• To determine if specific types of physical activity influence the risk of developing breast cancer, including subtypes.

Main Methods:

• Genome-wide association studies (GWAS) data from UK Biobank for PA phenotypes (n=460,376).
• Summary data for breast cancer (n=122,977 cases, 105,974 controls) from the BC Association Consortium.
• Two-sample Mendelian randomization (MR) using inverse variance weighted (IVW) and MR-PRESSO methods, with sensitivity analyses for heterogeneity and pleiotropy.

Main Results:

• Leisure walking showed a significant association with a decreased risk of estrogen receptor-positive breast cancer (ER+ BC) (OR = 0.302, p=0.027).
• No significant causal associations were found between other physical activities and breast cancer (BC), ER+ BC, or ER- BC.
• Reverse MR analysis indicated no significant causal effect of breast cancer on physical activity levels.

Conclusions:

• Leisure walking is associated with a reduced risk of ER+ BC.
• Further investigation is required to understand the mechanisms and confirm the causal link between leisure walking and breast cancer risk.