Exercising more and sitting down less can lower the risk of women developing breast cancer, according to a new study.
Observational studies have already shown a link between sedentary behavior and breast cancer risk but have not provided proof of causation.
Now, using a Mendelian randomization study – which use genetic variants as proxies for a specific risk factor such as lifelong sedentary behavior – researchers say they have found that proof by studying the genes of thousands of women.
“Increasing physical activity and reducing sedentary time are already recommended for cancer prevention," researchers said.
"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.”
Among the 130,957 women of European ancestry involved in the study, 69,838 had tumors that had spread locally (invasive) and 6,667 had tumors that hadn’t yet done so (in situ).
There was also a comparison group of 54,452 women who didn’t have breast cancer and all women in the study were participants of 76 studies supported by the Breast Cancer Association Consortium, a forum of investigators of breast cancer risk.
The researchers also drew on studies that had used data from UK Biobank to explore genetic predisposition to physical activity, vigorous physical activity or sitting time – measured by wrist-worn activity trackers – to predict how physically active or inactive their participants were.
Then they estimated breast cancer risk in relation to menopause, cancer type (positive for estrogen or progesterone, or HER-2, or positive/negative for all 3 hormones), stage (size and extent of tumor spread), and grade (degree of tumor cell abnormality).
Each group 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.
Among those, there were 46,528 estrogen receptor positive tumors and 11,246 controls; 34,891 progesterone receptor positive tumors and 16,432 controls; 6945 HER2 positive tumors and 33,214 controls; 1974 triple positive cases; and 4964 triple negative cases.
And there were 42,223 cases of invasive ductal/lobular cancers and 8795 controls, and 3510 cases of ductal carcinoma in situ; 17,583 stage 1 cancers, 15,992 stage 2, and 4553 stage 3-4; 34,647 moderately abnormal cell tumors and 16,432 highly abnormal cell tumors.
Analysis of the data showed that a higher overall level of genetically predicted physical activity was associated with a 41 percent lower risk of invasive breast cancer and this was largely irrespective of menopausal status, tumor type, stage, or grade.
Similarly, genetically predicted vigorous physical activity on three or more days of the week was associated with a 38 percent lower risk of breast cancer, compared with no self-reported vigorous activity.
These findings were consistent across most of the case groups.
Finally, a greater level of genetically predicted sitting time was associated with a 104 percent higher risk of triple negative breast cancer.
These findings were consistent across hormone-negative tumor types.
The results didn’t change even when genetically factoring in other unrelated effects such as smoking and being overweight.
The researchers said there are plausible explanations for their findings, highlighting a body of evidence that supports a causal relationship between physical activity and breast cancer risk, such as obesity, disordered metabolism, sex hormones and inflammation.
They also said their work provides strong evidence that more physical activity and less sitting time are likely to reduce breast cancer risk, adding: “Mechanisms linking sedentary time and cancer are likely to at least partially overlap with those underpinning the physical activity relationship.”
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