In this dual-sample investigation, we sought to unravel the causal relationships between 12 modifiable lifestyle parameters and breast pathologies. Our analyses revealed significant correlations between these modifiable lifestyle variables—such as years of schooling, pack years of smoking, sleep duration, household income, processed meat intake, fresh fruit intake and body mass index—and the incidence of breast diseases. It is important to note that while our findings offer valuable insights, their interpretation requires caution due to the complex interplay of multifactorial influences.
MR analysis revealed that more years of schooling, as predicted by genetic factors, is associated with reduced risks of overall BC,ER + BC, benign neoplasm of breast, and inflammatory disorders of breast. Previous investigations within European populations have not consistently established a link between years of schooling and breast disease risk Some studies suggest a lower risk of breast diseases with increased educational attainment, consistent with the findings presented here[26]. However, conflicting evidence, indicates that women with higher education levels may delay childbearing, resulting in fewer pregnancies and potentially increasing their susceptibility to breast cancer[27, 28]. In addition, individuals with higher educational levels may exhibit better adherence to screening protocols, leading to increased detection rates of breast cancer, although this may not necessarily translate to reduced mortality rates[29, 30].
Healthy dietary habits confer protection against cancer risk[31].Our research revealed a significant association between diet and breast cancer incidence. Increased intake of fresh fruits is correlated with a reduced risk of breast cancer, primarily attributed to their high content of polyphenolic compounds, endowing them with outstanding antioxidant activity, thus potentially mitigating cancer risk[32–34]. According to a meta-analysis comprising fifteen prospective studies, elevated fruit consumption was mildly associated with a decreased risk of breast cancer[35]. Furthermore, our investigation revealed a positive correlation between high consumption of meat and increased risk of ER-positive breast cancer. Studies suggest a link between high intake of processed meats and elevated breast cancer risk [36]. These findings align with our research outcomes, possibly attributable to the cytotoxicity induction, promotion of apoptosis and proliferation in epithelial cells, lipid peroxidation induction, free radical and DNA adduct formation in epithelial cells, and catalysis of N-nitroso compound formation, stemming from heme iron in red and processed meats, thereby fostering carcinogenesis[37].
Numerous epidemiological studies have underscored sleep duration as a risk factor for breast cancer[38–40]. Consistently, our findings revealed a positive association between shorter sleep duration and increased risk of breast disorders. Plausibly, sleep disturbances may perturb the homeostasis of various circulating hormones, including melatonin, cortisol, growth hormone, prolactin, glucose, and insulin, which are pivotal regulators implicated in diverse pathophysiological processes, notably breast carcinogenesis[41]. However, in a meta-analysis of 14 prospective studies and the Million Women Study, which included 65,410 breast cancer cases, short duration versus average sleep duration was not related with breast cancer risk[42]. So the association between sleep duration and breast cancer remains controversial[38, 43, 44].
Our research findings demonstrated a highly significant correlation between BMI and breast disease incidence. Obesity is widely acknowledged to be a risk factor for various cancers, including breast cancer. Studies have indicated that a genetically predisposed higher BMI is associated with lower serum testosterone levels[45], which in turn are positively correlated with breast cancer risk.[46, 47]. In premenopausal women, elevated BMI may mitigate breast cancer risk by decreasing estradiol levels.[48]. Moreover, obesity is a state characterized by chronic low-grade systemic inflammation and has been linked to various chronic conditions, notably breast diseases, in females[49]. Mounting evidence underscores the pivotal contribution of inflammatory adipokines and cytokines in predicting susceptibility to breast diseases among women[50–52].
A consolidated analysis of longitudinal studies revealed that smoking escalates the susceptibility to ER-positive breast cancer. Intriguingly, A comprehensive synthesis of cohort studies elucidates that early initiation of smoking is consistently linked with a slight elevation in risk, particularly evident among women who commenced smoking prior to their first full-term birth[53]. Conversely, findings from three large-scale cohort investigations indicate an inverse relationship between the duration of post-menopausal smoking and breast cancer risk, contrasting with a tendency towards increased risk in premenopausal smoker. This pattern mirrors observations in endometrial cancer, wherein post-menopausal smoking, but not premenopausal smoking, is associated with diminished risks[54]. Currently, there exists a paucity of studies pertaining to the association between smoking and breast pathologies, necessitating further investigation to elucidate the nexus between smoking and breast diseases.
The limitation of this study is that all participants included were of European descent. Therefore, it is uncertain whether the findings can be extrapolated to other ethnicities.