BMJ Magazine: It's a real hammer! Scientists analyzed data from more than 130,000 women and found a causal relationship between increased physical activity and reduced sedentary time and a reduced risk of breast cancer

*For medical professionals only

According to the latest WHO data, breast cancer has become the number one killer of female tumors in China, in every 5 female tumor patients, 1 is breast cancer, and in 2020 alone, more than 400,000 women suffer from different types of breast cancer, and the incidence is still younger [1].

Proportion of new-onset cancers among women in China (including Hong Kong, Macao and Taiwan) (2020)[1]

It is well known that improper lifestyle is one of the risk factors for
breast cancer.
Nowadays, even if you survive 996 day after day, you have to be squeezed dry by commuting, how can you have time to exercise! And the overloaded work pressure always makes girls more inclined to lie directly flat, brush mobile phones, chase dramas happy, sweat can not understand
.
As everyone knows, such an unhealthy lifestyle may be quietly brewing the risk of
breast cancer.

Previous observational studies have suggested that increased physical activity and/or reduced sedentary periods may be associated with a lower risk of breast cancer, but is the association causal or purely man-made bias? The inevitable confounding factors and reverse causal relationship are also always a stirring stick, resulting in the unclear causal relationship between "moving more and sitting less" and breast cancer risk
.
It's time to figure it out!

Recently, researchers from 143 research centers around the world (including the University of Cambridge, Melbourne Cancer Research Centre, etc.
) have published important research results in the BMJ sub-journal "British Journal of Sports Medicine" [2].

This large Mendelian randomisation (MR) study of more than 130,000 people confirmed that increased physical activity levels and reduced sedentary time reduced breast cancer risk, and for the first time strengthened the causal analysis
.

Specifically, genetically predicted more overall physical activity was associated with a lower risk of breast cancer (OR=0.
59); Strenuous activity was associated with a reduced risk of pre/perimenopausal breast cancer (OR=0.
62); Longer sedentary time is associated with a higher risk of hormone receptor-negative breast cancer (OR=1.
77), all in all, more activity and less sitting is beneficial to prevent breast cancer, and the benefits are also great
.

Screenshot of the front page of the paper

The benefits of increasing physical activity and reducing sitting are well known, and these two "killers" can not only reduce the risk of cardiovascular and cerebrovascular diseases, diabetes, obesity, depression, and even prevent a variety of tumors, which have long been recommended as the primary prevention
of cancer.

Among them, studies have shown that increased physical activity can reduce breast cancer risk, especially strenuous activity is most strongly associated with postmenopausal breast cancer risk [3].

However, the causal relationship is not clear, is it because high-intensity physical activity causes sedentary time to reduce the risk of breast cancer? Or is it breast cancer because sitting for too long leads to less physical activity? Many questions are not clearly answered
.

Only by going deep into the genetic level can it be possible to find the key to causality, and MR, which can reduce confusion and reverse causality, is a more powerful prediction tool, which uses genetic information as a substitute indicator to obtain a more solid causal relationship
.
Previous MR studies have predicted estrogen receptor (ER) status and found a potential causal relationship between higher levels of physical activity and a 49% reduction in breast cancer risk [4].

But what about the relationship between different breast cancer subtypes and vigorous activity/sedentary time?

With this in mind, the research team went a step further and used the Genome-wide Study (GWAS) associated with exercise in the UK Biobank database to make genetic model genetic predictions of single nucleotide polymorphisms (SNPs) related to overall physical activity, vigorous activity and sedentary time, and comprehensively assess the possible causal relationship
with overall breast cancer risk and pre- and post-menopause and different subtypes.

What are the benefits of this? Exercise-related gene tools identified by GWAS can greatly improve prediction accuracy and reduce error (error is typically estimated to be less than 1%)
compared to traditional self-reported collection of information.

The study included data from 130957 women in the Consortium of Breast Cancer Associations (BCAC), including 69,838 with invasive breast cancer and 6,667 with breast cancer in situ, and 54,452 participants
without breast cancer in the control group.
It also included information
on participants' height, weight, menopause, eating habits, drinking and smoking status, and breast cancer stage, grade, estrogen/progesterone (ER/PR) and HER2 status.

One image for participant details

Next, the team predicted physical activity (activity tool) or sedentary time (sedentary tool) by alleles, selected overall physical activity correlation (nsnps=5), sedentary time (nsnps=6), strenuous physical activity (accelerometer measurement, nsnps=1)/(self-report, nsnps=5), fitted a logistic regression model, and explored the association
between each SNP and individual outcomes.

Specifically, as a global physical activity assessment tool, five SNP gene variant data associated with overall activity (P<5×10-8</b10> vigorous physical activity, SNPs (P<5×10-9) equivalent to more than 6 metabolic equivalent (MET) strenuous activity and 5 SNPs (P<5×10-9) associated with <b14>self-reported

The data showed that genetically predicted increases in physical activity and reduced sedentary time were associated with a significant reduction in breast cancer risk: each 50 minutes/week increase in moderate-intensity physical activity after correcting for and excluding the effects of a pleioactive SNP was associated with a 41% reduction in the risk of aggressive breast cancer, 40% ER+ breast cancer risk, and 42% PR+ breast cancer risk, with no significant differences between different menopausal states, pathologic subtypes, stages, or
。

The association between overall physical activity and breast cancer risk was assessed by SNP gene prediction data

Compared with participants who rarely engaged in vigorous physical activity, genetically predicted self-reported vigorous physical activity (at least 10 minutes per day for more than 3 days/week) was associated with a 38% reduction in the risk of premenopausal/perimenopausal invasive breast cancer (95% CI 0.
45 to 0.
87), and no significant
protection against aggressive postmenopausal breast cancer.
In addition, vigorous physical activity was associated with a 23% reduction in the risk of PR+ breast cancer (95% CI 0.
61 to 0.
98), but not a significant
reduction in overall breast cancer and other types of breast cancer.

The association between strenuous activity and breast cancer risk was assessed by supplemental SNP gene prediction data and self-reporting methods

Finally, increasing sedentary time was associated with an increased risk of genetically predicted risk in almost every case group: each increase in sedentary time of about 7% was associated with a 77% increased risk of hormone-negative breast cancer, a 104% increased risk of triple-negative breast cancer, a 75% increase in the risk of breast carcinoma in situ, a 111% increase in the risk of ductal carcinoma in situ, a 62% increased risk of stage 1 breast cancer, a 20% increase in the risk of aggressive breast cancer, a 43% increase in the risk of ER-breast cancer, and a 40% increase in the risk of PR-breast cancer
。

To assess the correlation between sedentary time and breast cancer risk using SNP gene prediction data

In addition, the team found that women who were more physically active with genetic variants had a lower
risk of breast cancer for different breast cancer subtypes, stages or grades.
Of course, in addition to physical activity and sedentary time, sex hormone levels, inflammation, overweight or obesity, metabolic dysfunction and other factors may affect the risk of
breast cancer.

There are also some shortcomings in this study, such as the genetic variation data as an effect measure, which may still be prone to unfoldable and sparse data bias in some cases, resulting in unavoidable time bias issues
.
However, this study solves the dilemma of insufficient evidence and mixed conclusions on sedentary long-term work, and also fills the gap
of vigorous activity and different types of breast cancer that have not been involved in previous MR studies.
Researchers can also use this study to expand the causal relationship between other cancers and exercise/sedentary behavior, which is of great
clinical significance.

"Saint" strikes "all" to achieve lasting remission in the past 3 years with first-line treatment!

All in all, studies with such large sample sizes, while enhancing causation, provide strong evidence that "higher levels of physical activity and less sedentary time" reduce breast cancer risk and are consistent
across breast cancer subtypes.
For individual women, it is natural to inject another dose of strength into "more active and less sitting", once the increase in physical activity + reduce sedentary time, it is possible to reduce the risk of
breast cancer in the future.

Unfortunately, many people still go their own way and waste the opportunity to change/reverse the
occurrence of breast cancer.
The easiest way to reduce the greatest risk of breast cancer is why not? Hey! Say what about you (you)! Stop lying down/sitting and looking at your phone, take the first step of the Pink Revolution, and get moving!

References:

1.
https://gco.
iarc.
fr/today/data/factsheets/populations/160-China-fact-sheets.
pdf.

2.
Dixon-Suen SC, et al.
Physical activity, sedentary time and breast cancer risk: a Mendelian randomisation study.
Br J Sports Med.
2022;0:1–14.
doi:10.
1136/bjsports-2021-105132.

3.
World Cancer Research Fund International / American Institute for Cancer Research.
Continuous update project report: diet, nutrition, physical activity and breast cancer, 2017.

4.
Papadimitriou N, Dimou N, Tsilidis KK, et al.
Physical activity and risks of breast and colorectal cancer: a Mendelian randomisation analysis.
Nat Commun.
2020; 11(1):597.
Published 2020 Jan 30.
doi:10.
1038/s41467-020-14389-8.

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Responsible EditorTan Shuo