A study intended to support proof of causation has found that increasing levels of physical activity and reducing the time sitting could help to reduce the risk of breast cancer.1✅ JOURNAL REFERENCE
The Mendelian randomization study results were consistent for all stages and types of breast cancer, suggesting a stronger emphasis on exercise as a method for breast cancer prevention.
Mendelian randomization is a method that makes use of genetic variants as proxies for a specific risk factor to obtain genetic evidence supporting a causal relationship which in this case was lifelong sedentary behavior and levels of physical activity.
Although observational studies have shown that sedentary behavior and physical inactivity are associated with a higher risk of breast cancer, but they don’t prove breast cancer causation.
Mendelian randomization was therefore made used for assessing if lifelong sitting time and physical activity may be causally associated with the risk of breast cancer, especially for different tumor types.
Data were included from 130,957 women of which 69, 838 of them had locally spread invasive tumors, 6667 had in situ tumors that hadn’t yet spread, and 54,452 breast cancer-free women as a comparison group.
Data from previously published studies were used to genetically predict how physically inactive or active the participants in this study were.
The overall risk of breast cancer was then estimated, based on whether the women were or weren’t menopausal; and by type of cancer (positive for progesterone or estrogen, or HER-2, or negative/positive for all 3 hormones), cancer stage (extent and size of tumor spread), and cancer grade (tumor cell abnormality degree).
These case groups comprised 23,999 peri/pre-menopausal women who had breast cancer that was invasive and 17,686 women who didn’t have invasive breast cancer; 45,839 postmenopausal women who had breast cancer and 36,766 who didn’t have breast cancer.
46,528 tumors were estrogen receptor-positive with 11,246 controls; 34,891 tumors that were progesterone receptor positive with 16,432 controls; 6945 tumors that were HER2 positive with 33,214 controls; 1974 cases that were triple positive; and 4964 cases that were triple negative.
There were 42,223 invasive lobular/ductal cancer cases with 8795 controls, 3510 ductal carcinoma in situ cases; 17,583 cancers that were stage 1, 15,992 cancers that were stage 2, and 4553 cancers that were stage 3 to 4; 34,647 tumors that were moderately abnormal cell and 16,432 that were highly abnormal cell tumors.
Data analysis revealed that a higher genetically predicted physical activity level was linked to a 41% reduction in invasive breast cancer risk, and this was regardless of tumor type, grade, stage, or menopausal status.
Genetically predicted physical activity of vigorous-intensity on 3 days or more of the week was also linked to a 38% reduction in breast cancer risk, in comparison to no vigorous activity. These results were consistent for the majority of the case groups.
Also, a higher genetically predicted sitting time level was linked to a 104% greater triple-negative breast cancer risk. These results were consistent for all types of hormone-negative tumors.
Although reducing sedentary time and increasing physical activity are already recommended for preventing cancer, these study results provide significant evidence that less time sitting and more physical activity will help reduce the risk of breast cancer.