Although sedentary lifestyles and physical inactivity have been associated with an increased risk of breast cancer in observational studies, their causality has yet to be established.
Mendelian randomization is a method for obtaining genetic evidence for a causal association by using genetic variants as a proxy for a specific risk factor—in this example, lifetime physical activity levels/sedentary behavior.
A study led by Cancer Council Victoria in Australia, and including the Bristol Medical School: Population Health Sciences, is published online today, used Mendelian randomization to assess whether lifelong physical activity and sitting time might be causally related to breast cancer risk in general, and specifically to different types of tumor. It found that genetically predicted physical activity was associated with a 41% lower risk of invasive breast cancer.
The study, in other words, suggests that boosting physical activity levels and curbing sitting time are highly likely to lower breast cancer risk. The findings remain consistent across all types and stages of the disease, recommending a stronger focus on exercise to ward off breast cancer.
The study includes data from 130,957 women of European ancestry: 69,838 had tumors that had spread locally (invasive); 6,667 had tumors that hadn’t yet done so (in situ), and a comparison group of 54,452 women who didn’t have breast cancer. The women were participants in 76 studies under the aegis of the Breast Cancer Association Consortium (BCAC), a forum of investigators interested in the inherited risk of breast cancer.
To genetically predict how physically active or inactive their study participants were, the researchers drew on previously published studies that had used the vast repository of UK Biobank data on potential genetic explanations for general predisposition to physical activity, vigorous physical activity, or sitting time.
Next, they estimated overall breast cancer risk based on whether the women had or hadn’t gone through menopause; and by cancer type (positive for oestrogen or progesterone, or HER-2, or positive/negative for all three hormones), stage (size and extent of tumor spread), and grade (degree of tumor cell abnormality).
Scientists noted, “These case-control groups comprised: 23,999 pre/peri-menopausal women with invasive breast cancer and 17,686 women without; 45,839 postmenopausal women with breast cancer and 36,766 without.”
“In all, there were 46,528 oestrogen receptor positive tumours and 11,246 controls; 34,891 progesterone receptor positive tumours and 16,432 controls; 6,945 HER2 positive tumours and 33,214 controls; 1,974 triple positive ccases; and 4,964 triple negative cases.”
“There were 42,223 cases of invasive ductal/lobular cancers and 8,795 controls, and 3,510 cases of ductal carcinoma in situ; 17,583 stages, 15,992 stages 2, and 4,553 stage 3-4; 34,647 moderately abnormal cell tumors and 16,432 highly abnormal cell tumors.”
The results of the data analysis revealed that, regardless of menopausal status, tumor type, stage, or grade, a greater total level of genetically predicted physical activity was associated with a 41% decreased chance of developing invasive breast cancer.
Similarly, genetically predicted vigorous physical activity on three or more days of the week was linked to a 38% lower risk of breast cancer than no self-reported vigorous activity. Most of the case groups had similar results.
Finally, a higher amount of genetically predicted sitting time was linked to a 104% increased risk of breast cancer that is triple negative. These results held for all types of hormone-negative tumors.
Scientists say, “There are plausible biological explanations for their findings: a reasonable body of evidence indicating numerous causal pathways between physical activity and breast cancer risks, such as overweight/obesity, disordered metabolism, sex hormones, and inflammation.”
“Mechanisms linking sedentary time and cancer are likely to overlap with those underpinning the physical activity relationship partially.”
Associate Professor Brigid Lynch, Deputy Head of Cancer Epidemiology Division at the Cancer Council Victoria, Australia, and corresponding author, explained: “Increasing physical activity and reducing sedentary time are already recommended for cancer prevention. Our study adds further evidence that such behavioral changes are likely to lower the incidence of future breast cancer rates.
“A stronger cancer-control focus on physical activity and sedentary time as modifiable cancer risk factors is warranted, given the heavy burden of disease attributed to the most common cancer in women.”
Sarah Lewis, Professor of Molecular Epidemiology the in the Bristol Medical School: Population Health Sciences, MRC Integrative Epidemiology Unit, and a co-author, added: “This study shows that increasing overall physical activity levels and reducing sedentary time could protect against future breast cancer risk.
“Further work is ongoing to determine how physical activity affects cancer risk and to investigate the impact of physical activity on cancers at other sites.”
- Brigid M Lynch et al. in British Journal of Sports Medicine. Physical activity, sedentary time and breast cancer risk: a Mendelian randomization study